Energy balance and puberty onset: Emerging role of central mTOR signaling

Roa, Juan; Tena-Sempere, Manuel

doi:10.1016/j.tem.2010.05.003

Cited by 106Hypothalamic control of reproductive hormonesRegulation of Appetite and ObesityReproductive Biology and Fertility

Energy balance and puberty onset: Emerging role of central mTOR signaling

Roa, Juan, Tena-Sempere, Manuel·2010·Trends in Endocrinology & Metabolism

DOI 10.1016/j.tem.2010.05.003

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Abstract

The onset of puberty is gated by body energy reserves and nutritional cues. The adipose hormone leptin is an essential signal for the metabolic control of puberty, through mechanisms that are yet to be fully characterized. Mammalian target of rapamycin (mTOR), an energetic cell sensor, operates at specific hypothalamic nuclei as a transducer for leptin effects on feeding and energy homeostasis. This review summarizes recent experimental evidence supporting a role for central mTOR signaling in puberty onset. These findings are discussed in the context of topical developments in the field, such as recognition of the roles of the cAMP responsive element-binding protein regulated transcription coactivator-1 (Crtc1) and kisspeptins in the metabolic control of reproduction, thus highlighting novel mechanisms responsible for coupling puberty and energy homeostasis.

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In mammals, GnRH release is also regulated by the orexigenic neuropeptide Y (NPY) and kisspeptin, which relays both sex steroid and leptin signaling to GnRH neurons.
“In mammals, GnRH release is also regulated by the orexigenic neuropeptide Y (NPY) and kisspeptin, which relays both sex steroid and leptin signaling to GnRH neurons (49).”
From Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in Platynereis (2020) · cites this paper as [49]

The Physiology of Reproduction
Legendre, M., & Jalabert, B. (1988) · Annals of Internal Medicine · doi:10.7326/0003-4819-109-2-176_1 · Cited by 7,879 · see citing works
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787 · see citing works
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914 · see citing works
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766 · see citing works
AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799 · see citing works
mTOR signaling at a glance
Laplante, M., & Sabatini, D. (2009) · Journal of Cell Science · doi:10.1242/jcs.051011 · Cited by 2,317 · see citing works
Physiology of Reproduction
MAEDA, K., OHKURA, S., & Tsukamura, H. (2000) · Elsevier eBooks · doi:10.1016/b978-012426400-7/50048-0 · Cited by 2,135 · see citing works
TOR, a Central Controller of Cell Growth
Schmelzle, T., & Hall, M. N. (2000) · Cell · doi:10.1016/s0092-8674(00)00117-3 · Cited by 1,914 · see citing works
Two TOR Complexes, Only One of which Is Rapamycin Sensitive, Have Distinct Roles in Cell Growth Control
Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., Oppliger, W., Jenoe, P., & Hall, M. N. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00636-6 · Cited by 1,886 · see citing works
The Timing of Normal Puberty and the Age Limits of Sexual Precocity: Variations around the World, Secular Trends, and Changes after Migration
Parent, A.-S., Teilmann, G., Juul, A., Skakkebaek, N. E., Toppari, J., & Bourguignon, J.-P. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0019 · Cited by 1,762 · see citing works
PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure
Cantó, C., & Auwerx, J. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328328d0a4 · Cited by 1,624 · see citing works
Hypothalamic mTOR Signaling Regulates Food Intake
Cota, D., Proulx, K., Smith, K. A. B., Kozma, S. C., Thomas, G., Woods, S. C., & Seeley, R. J. (2006) · Science · doi:10.1126/science.1124147 · Cited by 1,278 · see citing works
Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span
Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. (2009) · Science · doi:10.1126/science.1177221 · Cited by 1,120 · see citing works
Kisspeptin Signaling in the Brain
Oakley, A. E., Clifton, D. K., & Steiner, R. A. (2009) · Endocrine Reviews · doi:10.1210/er.2009-0005 · Cited by 842 · see citing works
AMP-activated Protein Kinase Plays a Role in the Control of Food Intake
Andersson-Hall, U. K., Filipsson, K., Abbott, C. R., Woods, A., Smith, K. L., Bloom, S. R., Carling, D., & Small, C. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c300557200 · Cited by 755 · see citing works
S6K1 −/− / S6K2 −/− Mice Exhibit Perinatal Lethality and Rapamycin-Sensitive 5′-Terminal Oligopyrimidine mRNA Translation and Reveal a Mitogen-Activated Protein Kinase-Dependent S6 Kinase Pathway
Pende, M., Um, S. H., Mieulet, V., Sticker, M., Goss, V. L., Mestan, J., Mueller, M., Fumagalli, S., Kozma, S. C., & Thomas, G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.8.3112-3124.2004 · Cited by 743 · see citing works
Leptin Receptor Immunoreactivity in Chemically Defined Target Neurons of the Hypothalamus
Håkansson, M., Brown, H., Ghilardi, N., Skoda, R. C., & Meister, B. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-01-00559.1998 · Cited by 731 · see citing works
Disruption of the p70s6k/p85s6k gene reveals a small mouse phenotype and a new functional S6 kinase
Shima, H., Pende, M., Chen, Y., Fumagalli, S., THOMAS, G. V., & Kozma, S. C. (1998) · The EMBO Journal · doi:10.1093/emboj/17.22.6649 · Cited by 636 · see citing works
Recent decline in age at breast development: The Copenhagen Puberty Study
Aksglaede, L., Sørensen, K., Petersen, J. H., Skakkebæk, N. E., & Juul, A. (2009) · Pediatrics · doi:10.1542/peds.2008-2491 · Cited by 626 · see citing works
KiSS‐1 Neurones Are Direct Targets for Leptin in the ob/ob Mouse
Smith, J. T., Acohido, B. V., Clifton, D. K., & Steiner, R. A. (2006) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01417.x · Cited by 559 · see citing works
Changes in Hypothalamic KiSS-1 System and Restoration of Pubertal Activation of the Reproductive Axis by Kisspeptin in Undernutrition
Castellano, J. M., Navarro, V. M., Fernández-Fernández, R., Nogueiras, R., Tovar, S. A., Roa, J., Vazquez, M. J., Vigo, E., Casanueva, F. F., Aguilar, E., et al. (2005) · Endocrinology · doi:10.1210/en.2005-0337 · Cited by 557 · see citing works
Leptin's Actions on the Reproductive Axis: Perspectives and Mechanisms
Cunningham, M. J., Clifton, D. K., & Steiner, R. A. (1999) · Biology of Reproduction · doi:10.1095/biolreprod60.2.216 · Cited by 531 · see citing works
The expanding TOR signaling network
Martin, D. E., & Hall, M. N. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.02.008 · Cited by 496 · see citing works
Hypoinsulinaemia, glucose intolerance and diminished β-cell size in S6K1-deficient mice
Pende, M., Kozma, S. C., Jaquet, M., Oorschot, V. M. J., Burcelin, R., MARCHAND‐BRUSTEL, Y. L., Klumperman, J., Thorens, B., & Thomas, G. W. (2000) · Nature · doi:10.1038/35050135 · Cited by 452 · see citing works
Targeting mammalian target of rapamycin (mTOR) for health and diseases
Tsang, C. K., Qi, H., Liu, L. F., & Zheng, X. (2006) · Drug Discovery Today · doi:10.1016/j.drudis.2006.12.008 · Cited by 403 · see citing works
Novel signals for the integration of energy balance and reproduction
Fernandez-Fernandez, R., Martini, A. C., Navarro, V. M., Castellano, J. M., Diéguez, C., Aguilar, E., Pinilla, L., & Tena‐Sempere, M. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.04.026 · Cited by 385 · see citing works
Leptin Indirectly Regulates Gonadotropin-Releasing Hormone Neuronal Function
Quennell, J. H., Mulligan, A. C., Tups, A., Liu, X., Phipps, S. J., Kemp, C. J., Herbison, A. E., Grattan, D. R., & Anderson, G. M. (2009) · Endocrinology · doi:10.1210/en.2008-1693 · Cited by 385 · see citing works
New frontiers in kisspeptin/GPR54 physiology as fundamental gatekeepers of reproductive function
Roa, J., Aguilar, E., Diéguez, C., Pinilla, L., & Tena‐Sempere, M. (2007) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2007.07.002 · Cited by 343 · see citing works
The TOR pathway comes of age
Stanfel, M. N., Shamieh, L. S., Kaeberlein, M. R., & Kennedy, B. K. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.06.007 · Cited by 339 · see citing works
Role of mTOR in physiology and pathology of the nervous system
Swiech, L., Perycz, M., Malik, A., & Jaworski, J. (2008) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2007.08.015 · Cited by 338 · see citing works
Targeting the mTOR signaling network in cancer
Chiang, G. G., & Abraham, R. T. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.08.001 · Cited by 328 · see citing works
The Stimulatory Effect of Leptin on the Neuroendocrine Reproductive Axis of the Monkey 1
Finn, P. D., Cunningham, M. J., Pau, K. ‐. F., Spies, H. G., Clifton, D. K., & Steiner, R. A. (1998) · Endocrinology · doi:10.1210/endo.139.11.6297 · Cited by 294 · see citing works
Age at Puberty and the Emerging Obesity Epidemic
Aksglæde, L., Juul, A., Olsen, L. W., & Sørensen, T. I. A. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008450 · Cited by 269 · see citing works
Regulation of Hypothalamic Expression of KiSS-1 and GPR54 Genes by Metabolic Factors: Analyses Using Mouse Models and a Cell Line
Luque, R. M., Kineman, R. D., & Tena‐Sempere, M. (2007) · Endocrinology · doi:10.1210/en.2007-0500 · Cited by 261 · see citing works
Physiology of the Adult Gonadotropin-Releasing Hormone Neuronal Network
Herbison, A. E. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00011-9 · Cited by 255 · see citing works
Expression of Hypothalamic KiSS-1 System and Rescue of Defective Gonadotropic Responses by Kisspeptin in Streptozotocin-Induced Diabetic Male Rats
Castellano, J. M., Navarro, V. M., Fernández-Fernández, R., Roa, J., Vigo, E., Pineda, R., Diéguez, C., Aguilar, E., Pinilla, L., & Tena‐Sempere, M. (2006) · Diabetes · doi:10.2337/db05-1584 · Cited by 249 · see citing works
The Mammalian Target of Rapamycin as Novel Central Regulator of Puberty Onset via Modulation of Hypothalamic Kiss1 System
Roa, J., García-Galiano, D., Varela, L., Sanchez-Garrido, M. A., Pineda, R., Castellano, J. M., Ruíz-Pino, F., Romero, M., Aguilar, E., López, M., et al. (2009) · Endocrinology · doi:10.1210/en.2009-0096 · Cited by 247 · see citing works
Postnatal Development of an Estradiol-Kisspeptin Positive Feedback Mechanism Implicated in Puberty Onset
Clarkson, J., Boon, W. C., Simpson, E. R., & Herbison, A. E. (2009) · Endocrinology · doi:10.1210/en.2008-1733 · Cited by 232 · see citing works
Amino acid signalling and the integration of metabolism
Meijer, A. J., & Dubbelhuis, P. F. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.07.012 · Cited by 215 · see citing works
Early Metabolic Programming of Puberty Onset: Impact of Changes in Postnatal Feeding and Rearing Conditions on the Timing of Puberty and Development of the Hypothalamic Kisspeptin System
Castellano, J. M., Overgaard, A., Sanchez-Garrido, M. A., Ruíz-Pino, F., Romero, M., García-Galiano, D., Aguilar, E., Pinilla, L., Diéguez, C., Mikkelsen, J. D., et al. (2011) · Endocrinology · doi:10.1210/en.2010-1415 · Cited by 206 · see citing works
The Creb1 coactivator Crtc1 is required for energy balance and fertility
Altarejos, J. Y., Goebel, N., Conkright, M. D., Inoue, H., Xie, J., Arias, C. M., Sawchenko, P. E., & Montminy, M. (2008) · Nature Medicine · doi:10.1038/nm.1866 · Cited by 200 · see citing works
The Role of Hypothalamic Mammalian Target of Rapamycin Complex 1 Signaling in Diet-Induced Obesity
Cota, D., Matter, E. K., Woods, S. C., & Seeley, R. J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1389-08.2008 · Cited by 191 · see citing works
Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism
Morrison, C. D., Xi, X., White, C. L., Ye, J., & Martin, R. J. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00675.2006 · Cited by 183 · see citing works
Metabolic control of puberty onset: New players, new mechanisms
Roa, J., García-Galiano, D., Castellano, J. M., Gaytán, F., Pinilla, L., & Tena‐Sempere, M. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.12.018 · Cited by 174 · see citing works
KiSS-1/kisspeptins and the metabolic control of reproduction: Physiologic roles and putative physiopathological implications
Castellano, J. M., Roa, J., Luque, R. M., Diéguez, C., Aguilar, E., Pinilla, L., & Tena‐Sempere, M. (2008) · Peptides · doi:10.1016/j.peptides.2008.06.007 · Cited by 166 · see citing works
Neuroendocrinology in Physiology and Medicine
(2000) · Humana Press eBooks · doi:10.1007/978-1-59259-707-9 · Cited by 148 · see citing works
Development of Leptin‐Sensitive Circuits
Bouret, S. G., & Simerly, R. B. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01563.x · Cited by 143 · see citing works
Roles of ghrelin and leptin in the control of reproductive function
Tena-Sempere, M. (2007) · Neuroendocrinology · doi:10.1159/000108410 · Cited by 141 · see citing works
Glial–Gonadotrophin Hormone (GnRH) Neurone Interactions in the Median Eminence and the Control of GnRH Secretion
Ojeda, S., Lomniczi, A., & Sandau, U. (2008) · Journal of neuroendocrinology · doi:10.1111/j.1365-2826.2008.01712.x · Cited by 139 · see citing works
Physiology of the Gonadotropin-Releasing Hormone Neuronal Network
Herbison, A. E. (2006) · Elsevier eBooks · doi:10.1016/b978-012515400-0/50033-6 · Cited by 139 · see citing works
Globular adiponectin inhibits GnRH secretion from GT1-7 hypothalamic GnRH neurons by induction of hyperpolarization of membrane potential
Wen, J., Lv, W., Yang, J., Nie, A., Cheng, X., Yang, Y., Ge, Y., Li, X.-Y., & Ning, G. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.04.146 · Cited by 135 · see citing works
Control of GnRH neuronal activity by metabolic factors: The role of leptin and insulin
Gamba, M., & Pralong, F. P. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.04.023 · Cited by 135 · see citing works
Expression of a Leptin Receptor in Immortalized Gonadotropin-Releasing Hormone-Secreting Neurons
Magni, P., Vettor, R., Pagano, C., Calcagno, A., Beretta, E., Messi, E., ZANISI, M., Martini, L., & Motta, M. (1999) · Endocrinology · doi:10.1210/endo.140.4.6622 · Cited by 132 · see citing works
Regulation of Food Intake Through Hypothalamic Signaling Networks Involving mTOR
Woods, S. C., Seeley, R. J., & Cota, D. (2008) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.28.061807.155505 · Cited by 125 · see citing works
The Stimulatory Effect of Leptin on the Neuroendocrine Reproductive Axis of the Monkey
Finn, P. D. (1998) · Endocrinology · doi:10.1210/en.139.11.4652 · Cited by 120 · see citing works
The Role of CNS Fuel Sensing in Energy and Glucose Regulation
Cota, D., Proulx, K., & Seeley, R. J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.049 · Cited by 117 · see citing works
Neurobiological mechanisms underlying kisspeptin activation of gonadotropin-releasing hormone (GnRH) neurons at puberty
Clarkson, J., Han, S., Liu, X., Lee, K., & Herbison, A. E. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.01.026 · Cited by 115 · see citing works
Fasting Reduces KiSS‐1 Expression in the Anteroventral Periventricular Nucleus (AVPV): Effects of Fasting on the Expression of KiSS‐1 and Neuropeptide Y in the AVPV or Arcuate Nucleus of Female Rats
Κalamatianos, T., Grimshaw, S. E., Poorun, R., Hahn, J. D., & Coen, C. W. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01757.x · Cited by 101 · see citing works
New Concepts on the Control of the Onset of Puberty
Ojeda, S. R., Lomniczi, A., Sandau, U. S., & Matagne, V. (2009) · Endocrine development · doi:10.1159/000262527 · Cited by 85 · see citing works
Expression of a Tumor-Related Gene Network Increases in the Mammalian Hypothalamus at the Time of Female Puberty
Roth, C. L., Mastronardi, C. A., Lomniczi, A., Wright, H., Cabrera, R., Mungenast, A. E., Heger, S., Jung, H., Dubay, C., & Ojeda, S. R. (2007) · Endocrinology · doi:10.1210/en.2007-0634 · Cited by 83 · see citing works
Complex Regulation of Mammalian Target of Rapamycin Complex 1 in the Basomedial Hypothalamus by Leptin and Nutritional Status
Villanueva, E. C., Münzberg, H., Cota, D., Leshan, R. L., Kopp, K., Ishida-Takahashi, R., Jones, J. C., Fingar, D. C., Seeley, R. J., & Myers, M. G. (2009) · Endocrinology · doi:10.1210/en.2009-0642 · Cited by 81 · see citing works
Neuroendocrinology in physiology and medicine
Kremer, J. A. M. (2000) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/s0301-2115(00)00249-9 · Cited by 81 · see citing works
Reproductive Medicine: Molecular, Cellular and Genetic Fundamentals
Penzias, A. S. (2003) · JAMA · doi:10.1001/jama.290.22.3005-a · Cited by 69 · see citing works
The Effect of AMP‐Activated Kinase Activation on Gonadotrophin‐Releasing Hormone Secretion in GT1‐7 Cells and its Potential Role in Hypothalamic Regulation of the Oestrous Cyclicity in Rats
Coyral-Castel, S., Tosca, L., Ferreira, G., Jeanpierre, E., Ramé, C., Lomet, D., Caraty, A., Monget, P., Chabrolle, C., & Dupont, J. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2007.01643.x · Cited by 67 · see citing works
Fatty Acid Synthase Inhibitors Modulate Energy Balance via Mammalian Target of Rapamycin Complex 1 Signaling in the Central Nervous System
Proulx, K., Cota, D., Woods, S. C., & Seeley, R. J. (2008) · Diabetes · doi:10.2337/db07-1690 · Cited by 57 · see citing works
Neuroendocrine Regulation of Reproductive Cyclicity
Schwartz, N. B. (2000) · Humana Press eBooks · doi:10.1007/978-1-59259-707-9_8 · Cited by 56 · see citing works
Reproductive medicine : molecular, cellular and genetic fundamentals
Fauser, B. C. J. M. (2003) · Parthenon eBooks · Cited by 56 · see citing works
Roles of Kisspeptins in the Control of Hypothalamic-Gonadotropic Function: Focus on Sexual Differentiation and Puberty Onset
Tena‐Sempere, M. (2009) · Endocrine development · doi:10.1159/000262528 · Cited by 53 · see citing works
γ-Aminobutyric Acid and Glutamate Differentially Regulate Intracellular Calcium Concentrations in Mouse Gonadotropin-Releasing Hormone Neurons
Constantin, S., Jasoni, C. L., Wadas, B. C., & Herbison, A. E. (2009) · Endocrinology · doi:10.1210/en.2009-0817 · Cited by 49 · see citing works
Mouse fertility is not dependent on the CREB coactivator Crtc1
Breuillaud, L., Halfon, O., Magistretti, P. J., Pralong, F. P., & Cardinaux, J. (2009) · Nature Medicine · doi:10.1038/nm0909-989 · Cited by 42 · see citing works
Gonadotropins and gonadotropin receptors
Huhtaniemi, I. T., & Alevizaki, M. K. (2010) · CRC Press eBooks · doi:10.3109/9781841847474-24 · Cited by 40 · see citing works
Clinical aspects of male sex differentiation
Svensson, J., & Giwercman, Y. L. (2010) · CRC Press eBooks · doi:10.3109/9781841847474-26 · Cited by 35 · see citing works
Effects of galanin-like peptide on luteinizing hormone secretion in the rat: sexually dimorphic responses and enhanced sensitivity at male puberty
Castellano, J. M., Navarro, V. M., Fernández-Fernández, R., Roa, J., Vigo, E., Pineda, R., Steiner, R. A., Aguilar, E., Pinilla, L., & Tena‐Sempere, M. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00130.2006 · Cited by 34 · see citing works
Energetic cell sensors: a key to metabolic homeostasis
Naïmi, M., Arous, C., & OBBERGHEN, E. V. (2009) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2009.09.003 · Cited by 31 · see citing works

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“[Adapted from Roa and Tena-Sempere (377).]”
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Background
Early Metabolic Programming of Puberty Onset: Impact of Changes in Postnatal Feeding and Rearing Conditions on the Timing of Puberty and Development of the Hypothalamic Kisspeptin System
Castellano, J. M., Overgaard, A., Sanchez-Garrido, M. A., Ruíz-Pino, F., Romero, M., García-Galiano, D., Aguilar, E., Pinilla, L., Diéguez, C., Mikkelsen, J. D., et al. (2011) · Endocrinology · doi:10.1210/en.2010-1415 · Cited by 206 · see citing works
“stress on Kiss1 expression and gonadotropin responsiveness to Kp had been previously explored in pubertal and adult animals (45, 46), the impact of early (postnatal) metabolic challenges on the subsequent expression and function of the hypothalamic Kiss1 system later during puberty remains largely unexplored to date.”
BackgroundInfluential
Leptin signaling and circuits in puberty and fertility
Elias, C. F., & Purohit, D. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1095-1 · Cited by 190 · see citing works
“A role for mTOR in the neuroendocrine reproductive axis of the female rats was reported [273, 274].”
Background
Female reproduction and type 1 diabetes: From mechanisms to clinical findings
Codner, E., Merino, P. M., & Tena-Sempere, M. (2012) · Human Reproduction Update · doi:10.1093/humupd/dms024 · Cited by 182 · see citing works
“These metabolic signals are essential for the joint regulation of energy homeostasis and reproduction (Fernandez- Fernandez et al., 2006; Roa et al., 2008; Pralong, 2010; Roa and Tena- Sempere, 2010).”
Background
Neuroendocrine control by kisspeptins: role in metabolic regulation of fertility
Navarro, V. M., & Tena‐Sempere, M. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.147 · Cited by 177 · see citing works
Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: revision of human observations and mechanistic insight from rodents
Parent, A.-S., Franssen, D., Fudvoye, J., Gérard, A., & Bourguignon, J.-P. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.12.004 · Cited by 175 · see citing works
“For instance, prepubertal restriction or excess of food and adiposity may lead to delayed or early puberty, respectively (Biro et al., 2006; Dunger et al., 2006; Ong et al., 2004, 2006; Cheng et al., 2012; Himes, 2006; Roa and Tena-Sempere, 2010) whereas intrauterine growth restriction is associated with early puberty…”
Influential
Leptin action in pubertal development: recent advances and unanswered questions
Elias, C. F. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.09.002 · Cited by 145 · see citing works
“In recent years, a series of important findings have suggested a role for cAMP responsive element-binding protein regulated transcription coactivator-1 (Crtc1) and mTOR as potential signaling pathways linking energy balance and reproduction (17, 84, 85).”
BackgroundInfluential
Kisspeptins in Reproductive Biology: Consensus Knowledge and Recent Developments1
Roa, J., Navarro, V. M., & Tena‐Sempere, M. (2011) · Biology of Reproduction · doi:10.1095/biolreprod.111.091538 · Cited by 142 · see citing works
“In this context, recent efforts have been devoted to elucidate the molecular mechanisms whereby leptin modulates Kiss1 expression and reproductive function; the Creb coactivator and the mammalian target of rapamycin are likely involved in this phenomenon [94, 101, 102].”
Background
Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty
Avendaño, M. S., Vazquez, M. J., & Tena‐Sempere, M. (2017) · Human Reproduction Update · doi:10.1093/humupd/dmx025 · Cited by 139 · see citing works
Connecting metabolism and reproduction: roles of central energy sensors and key molecular mediators
Roa, J., & Tena-Sempere, M. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.09.027 · Cited by 136 · see citing works
“…suggests that, in addition to its central actions on energy homeostasis, brain mTOR signaling is also involved in the metabolic regulation of the HPG axis, and specifically in conveying, at least part of, the modulatory effects of leptin onto the reproductive brain (Roa and Tena-Sempere, 2010).”
Hypothalamic mTOR Signaling Mediates the Orexigenic Action of Ghrelin
Martins, L., Fernández-Mallo, D., Novelle, M. G., Vazquez, M. J., Tena‐Sempere, M., Nogueiras, R., López, M., & Diéguez, C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046923 · Cited by 131 · see citing works
“[15–19].”
The Still Dark Side of the Moon: Molecular Mechanisms of Lunar-Controlled Rhythms and Clocks
Andreatta, G., & Tessmar-Raible, K. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.03.009 · Cited by 111 · see citing works
Early puberty in 11-year-old girls: Millennium Cohort Study findings
Kelly, Y. J., Zilanawala, A., Sacker, A., Hiatt, R. A., & Viner, R. (2016) · Archives of Disease in Childhood · doi:10.1136/archdischild-2016-310475 · Cited by 109 · see citing works
Mechanisms of lipid metabolism in uterine receptivity and embryo development
Ye, Q., Zeng, X., Cai, S., Qiao, S., & Zeng, X. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.09.002 · Cited by 96 · see citing works
Novel mechanisms for the metabolic control of puberty: implications for pubertal alterations in early-onset obesity and malnutrition
Vazquez, M. J., Velasco, I., & Tena‐Sempere, M. (2019) · Journal of Endocrinology · doi:10.1530/joe-19-0223 · Cited by 90 · see citing works
“Contrary to AMPK, mTOR is activated in situations of energy excess to promote anabolic pathways, the inter-relationship between AMPK and mTOR being fundamental in the control of numerous cellular activities (Roa & Tena-Sempere 2010, Lopez et al.”
Background
Neuroanatomical Framework of the Metabolic Control of Reproduction
Hill, J. W., & Elias, C. F. (2018) · Physiological Reviews · doi:10.1152/physrev.00033.2017 · Cited by 79 · see citing works
“The mTOR pathway also controls the HPG axis and the onset of puberty (379, 381).”
Background
Metabolic regulation of female puberty via hypothalamic AMPK–kisspeptin signaling
Roa, J., Barroso, A., Ruíz-Pino, F., Vazquez, M. J., Seoane‐Collazo, P., Martínez‐Sánchez, N., García-Galiano, D., İlhan, T., Pineda, R., León, S., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1802053115 · Cited by 79 · see citing works
“We have previously documented that hypothalamic signaling via the mammalian target of rapamycin (mTOR) interplays with Kiss1 in the metabolic control of puberty (28, 45).”
Background
ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms
Tena‐Sempere, M. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0669 · Cited by 76 · see citing works
Age-dependent effects in fathead minnows from the anti-diabetic drug metformin
Crago, J., Bui, C. V., Grewal, S., & Schlenk, D. (2016) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2015.12.030 · Cited by 70 · see citing works
Current Changes in Pubertal Timing: Revised Vision in Relation with Environmental Factors Including Endocrine Disruptors
Parent, A., Franssen, D., Fudvoye, J., Pinson, A., & Bourguignon, J.-P. (2015) · Endocrine development · doi:10.1159/000438885 · Cited by 70 · see citing works
Complications of mammalian target of rapamycin inhibitor anticancer treatment among patients with tuberous sclerosis complex are common and occasionally life-threatening
Trelińska, J., Dachowska, I., Kotulska, K., Fendler, W. M., Jóźwiak, S., & Mlynarski, W. M. (2015) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000000207 · Cited by 67 · see citing works
The Genetic Basis of Delayed Puberty
Howard, S. R., & Dunkel, L. (2017) · Neuroendocrinology · doi:10.1159/000481569 · Cited by 62 · see citing works
Corazonin signaling integrates energy homeostasis and lunar phase to regulate aspects of growth and sexual maturation in Platynereis
Andreatta, G., Broyart, C., Borghgraef, C., Vadiwala, K., Kozin, V., Polo, A., Bileck, A., Beets, I., Schoofs, L., Gerner, C., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1910262116 · Cited by 61 · see citing works
“In mammals, GnRH release is also regulated by the orexigenic neuropeptide Y (NPY) and kisspeptin, which relays both sex steroid and leptin signaling to GnRH neurons (49).”
Background
Management of side effects of mTOR inhibitors in tuberous sclerosis patients
Sadowski, K., Kotulska, K., & Jóźwiak, S. (2016) · Pharmacological Reports · doi:10.1016/j.pharep.2016.01.005 · Cited by 60 · see citing works
Body Weight Impact on Puberty: Effects of High-Calorie Diet on Puberty Onset in Female Rhesus Monkeys
Terasawa, E., Kurian, J. R., Keen, K. L., Shiel, N. A., Colman, R. J., & Capuano, S. (2012) · Endocrinology · doi:10.1210/en.2011-1970 · Cited by 59 · see citing works
“leptin signaling) and reproductive function has also emerged (67, 68).”
Background
The Genetic Basis of Delayed Puberty
Howard, S. R. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00423 · Cited by 59 · see citing works
“These afferents are likely to include LEPRexpressing GABA neurons from the arcuate nucleus, nitric oxide (which is required for its action) pathways, mTOR signaling, as well as kisspeptin/neuropeptide Y neurons (30, 31).”
Background
Gerosuppressant Metformin: less is more
Menéndez, J. A., Cufí, S., Oliveras‐Ferraros, C., Vellón, L., Joven, J., & Vázquez‐Martín, A. (2011) · Aging · doi:10.18632/aging.100316 · Cited by 57 · see citing works
“Moreover, the well-recognized ability of CR-induced deactivation of the mTOR pathway to slow growth, fitness and the onset of reproduction [10-12] while reducing risk of cancer (i.”
Background
Neuropeptide Y and Metabolism Syndrome: An Update on Perspectives of Clinical Therapeutic Intervention Strategies
Huang, Y., Lin, X., & Lin, S. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.695623 · Cited by 58 · see citing works
“…inflammation affects both NPY and POMC and promotes obesity. mTOR Signaling Mammalian target of rapamycin (mTOR) is a serine-theonine kinase as a sensor of energy balance, nutrients and oxygen (Roa and Tena-Sempere, 2010). mTOR is expressed in AgRP/NPY neurons in the ARC (Cota et al., 2006).”
Background
The interference of DEHP in precocious puberty of females mediated by the hypothalamic IGF-1/PI3K/Akt/mTOR signaling pathway
Shao, P., Wang, Y., Zhang, M., Wen, X., Zhang, J., Xu, Z., Hu, M., Jiang, J., & Liu, T. (2019) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2019.06.017 · Cited by 53 · see citing works
Everolimus for the Treatment of Tuberous Sclerosis Complex–Related Cardiac Rhabdomyomas in Pediatric Patients
Dahdah, N. (2017) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2017.06.076 · Cited by 50 · see citing works
S6K1 in the Central Nervous System Regulates Energy Expenditure via MC4R/CRH Pathways in Response to Deprivation of an Essential Amino Acid
Xia, T., Cheng, Y., Zhang, Q., Xiao, F., Liu, B., Chen, S., & Guo, F. (2012) · Diabetes · doi:10.2337/db11-1278 · Cited by 48 · see citing works
“In addition to a large number of studies investigating a role for mTOR in the regulation of energy homeostasis (23,28,31,32), which provide indirect evidence for a role of S6K1 in the regulation of energy homeostasis, recent studies have also provided evidence for a role of S6K1 FIG.”
Background
Keeping Puberty on Time
Tena‐Sempere, M. (2013) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-396968-2.00011-7 · Cited by 46 · see citing works
“Detailed description of the physiological roles of mTOR in the control of cellular energy homeostasis and food intake can be found elsewhere (Roa & Tena-Sempere, 2010).”
Background
Rat BAT xenotransplantation recovers the fertility and metabolic health of PCOS mice
Du, L., Wang, Y., Li, C., Chen, L.-J., Cai, J.-Y., Xia, Z., Zeng, W., Wang, Z., Chen, X., Hu, F., et al. (2020) · Journal of Endocrinology · doi:10.1530/joe-20-0068 · Cited by 46 · see citing works
“Fourth, mTOR activity is important for maintaining normal metabolism, and abnormal mTOR activity levels in PCOS mice are related to abnormal energy production (Roa & Tena-Sempere 2010, Hung et al.”
Background
Leptin regulates neuropeptides associated with food intake and GnRH secretion
Guzmán, A., Hernández‐Coronado, C. G., Rosales‐Torres, A. M., & Hernandez-Medrano, J. H. (2018) · Annales d Endocrinologie · doi:10.1016/j.ando.2018.07.012 · Cited by 47 · see citing works
Intracellular amino acid sensing and mTORC1-regulated growth: new ways to block an old target?
Goberdhan, D. C. I. (2010) · PubMed · Cited by 45 · see citing works
Knockdown of leptin A expression dramatically alters zebrafish development
Liu, Q., Dalman, M. R., Chen, Y., Akhter, M., Brahmandam, S., Patel, Y., Lowe, J., Thakkar, M., Gregory, A.-V., Phelps, D., et al. (2012) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2012.07.011 · Cited by 44 · see citing works
“That body of work revealed that leptin is a pleiotropic hormone, with well described effects on lipid metabolism, thermoregulation, immune function, reproductive maturation, angiogenesis, and bone remodeling (see [6, 14, 15,25, 47, 49] for reviews).”
Background
Review of the role of leptin in the regulation of male reproductive function
Zhang, J., & Gong, M. (2018) · Andrologia · doi:10.1111/and.12965 · Cited by 44 · see citing works
Ghrelin, the Gonadal Axis and the Onset of Puberty
Tena‐Sempere, M. (2013) · Endocrine development · doi:10.1159/000346055 · Cited by 42 · see citing works
Role of the adipocyte-derived hormone leptin in reproductive control
García-Galiano, D., Allen, S. J., & Elias, C. F. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2014-0017 · Cited by 40 · see citing works
“mTOR is a serine/threonine kinase downstream of the PI3K-Akt pathway with a key role in multiple functions, including the neuroendocrine control of the reproductive axis [89].”
Background
Amino Acids and TOR Signaling Promote Prothoracic Gland Growth and the Initiation of Larval Molts in the Tobacco Hornworm Manduca sexta
Kemirembe, K., Liebmann, K., Bootes, A. M., Smith, W. A., & Suzuki, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044429 · Cited by 37 · see citing works
“mTOR appears to act upstream of kisspeptin and GnRH in vertebrates [47,48,49,50].”
Background
Rola sygnalizacji kisspeptyny w osi podwzgórze–przysadka–nadnercza — aktualna perspektywa
Javed, Z., Qamar, U., & Sathyapalan, T. (2015) · Endokrynologia Polska · doi:10.5603/ep.2015.0066 · Cited by 30 · see citing works
“These findings attracted substantial attention and have been the subject of rigorous analysis in various mammalian and non-mammalian species [92, 129] and the current available neuroanatomical and functional evidence, although mainly in rodents, strongly supports the role of kisspeptins in triggering the onset of pube…”
Background
RNA-seq analysis of lncRNA-controlled developmental gene expression during puberty in goat & rat
Gao, X., Ye, J., Chen, Y., Luo, L., Liu, Y., Ding, J., Zhang, Y., Ling, Y., Huang, W., Zhang, X., et al. (2018) · BMC Genetics · doi:10.1186/s12863-018-0608-9 · Cited by 29 · see citing works
“As showed previously, the AMPK signaling pathway was a novel regulator of GnRH release, which played an important role in regulating puberty and reproduction [54, 55].”
Background
mTOR signaling in the arcuate nucleus of the hypothalamus mediates the anorectic action of estradiol
González‐García, I., de Morentin, P. B. M., Estévez‐Salguero, Á., Contreras, C., Romero, A., Fernø, J., Nogueiras, R., Diéguez, C., Tena‐Sempere, M., Tovar, S. A., et al. (2018) · Journal of Endocrinology · doi:10.1530/joe-18-0190 · Cited by 28 · see citing works
“Specifically, hypothalamic mTOR controls puberty onset and gonadotropin secretion by regulation of Kiss1 (Roa et al. 2009, Roa & Tena-Sempere 2010).”
Calorie Restriction Modulates Reproductive Development and Energy Balance in Pre-Pubertal Male Rats
Rizzoto, G., Sekhar, D., Thundathil, J. C., Chelikani, P. K., & Kastelic, J. P. (2019) · Nutrients · doi:10.3390/nu11091993 · Cited by 26 · see citing works
“It is well documented that metabolic hormones including leptin, IGF-1 and insulin communicate level of body tissue reserves to the hypothalamic-pituitary-gonadal (HPG) axis [11,16,40], emphasizing importance of studying impacts of nutrition and refeeding on above-described hormones.”
Background
Emerging Roles of Epigenetics in the Control of Reproductive Function: Focus on Central Neuroendocrine Mechanisms
Vazquez, M. J., Daza‐Dueñas, S., & Tena‐Sempere, M. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab152 · Cited by 28 · see citing works
“Although the precise molecular mechanisms by which the information conveyed by this plethora of metabolic hormones is transmitted to the brain centers governing the reproductive axis are not completely elucidated, experimental studies conducted by our group in recent years have focused on addressing the potential role…”
Background
Animal Modeling of Early Programming and Disruption of Pubertal Maturation
Castellano, J. M., & Tena‐Sempere, M. (2015) · Endocrine development · doi:10.1159/000438877 · Cited by 27 · see citing works
Contribution of the Endocrine Perspective in the Evaluation of Endocrine Disrupting Chemical Effects: The Case Study of Pubertal Timing
Bourguignon, J.-P., Juul, A., Franssen, D., Fudvoye, J., Pinson, A., & Parent, A. (2016) · Hormone Research in Paediatrics · doi:10.1159/000442748 · Cited by 27 · see citing works
Arginine, histidine and tryptophan: A new hope for cancer immunotherapy
Tantawy, A. A., & Naguib, D. M. (2019) · PharmaNutrition · doi:10.1016/j.phanu.2019.100149 · Cited by 27 · see citing works
Lin28 gene and mammalian puberty
Cao, G., Gao, Z., Jiang, Y., & Chu, M. (2020) · Molecular Reproduction and Development · doi:10.1002/mrd.23347 · Cited by 24 · see citing works
EFFECTS: an expanded access program of everolimus for patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex
Fogarasi, A., Waele, L. D., Bartalini, G., Jóźwiak, S., Laforgia, N., Verhelst, H., Petrak, B., Pédespan, J., Witt, O., Castellana, R., et al. (2016) · BMC Neurology · doi:10.1186/s12883-016-0658-4 · Cited by 24 · see citing works
“While some data indicate that mTOR inhibition may partly be associated with the control of puberty onset [32], it has also been suggested that amenorrhea could be caused by TSC per se and may not be related to the treatment with mTOR inhibitors [33].”
Background
Immunohistochemical localization and possible functions of nesfatin-1 in the testis of mice during pubertal development and sexual maturation
Ranjan, A. K., Choubey, M., Yada, T., & Krishna, A. (2019) · Journal of Molecular Histology · doi:10.1007/s10735-019-09846-8 · Cited by 23 · see citing works
Granulosa cells of prepubertal cattle respond to gonadotropin signaling and upregulate genes that promote follicular growth and prevent cell apoptosis
Michalovic, L., Currin, L., Gutierrez, K., Bellefleur, A., Glanzner, W. G., Schuermann, Y., de Macedo, M. P., Bohrer, R. C., Dicks, N., Lopez, R., et al. (2018) · Molecular Reproduction and Development · doi:10.1002/mrd.23066 · Cited by 22 · see citing works
Factors affecting response to everolimus therapy for subependymal giant cell astrocytomas associated with tuberous sclerosis
Trelińska, J., Dachowska, I., Kotulska, K., Barańska, D., Fendler, W. M., Jóźwiak, S., & Mlynarski, W. M. (2015) · Pediatric Blood & Cancer · doi:10.1002/pbc.25368 · Cited by 21 · see citing works
“These observations support a central role for mTOR signaling in pubertal onset and necessitate further investigations of potential effects of everolimus on growth, development and sexual maturation in children [9,19].”
Background
Methylation of Hypothalamic Tsc1‐mTOR Signaling in Regulation of Obesity and Obesity Resistance
Wang, Y., Diao, S., Hu, M., & Zhang, L. (2020) · BioMed Research International · doi:10.1155/2020/8723869 · Cited by 20 · see citing works
Pooled analysis of menstrual irregularities from three major clinical studies evaluating everolimus for the treatment of tuberous sclerosis complex
Sparagana, S. P., Franz, D. N., Krueger, D. A., Bissler, J. J., Berkowitz, N. C., Burock, K., & Kingswood, J. C. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186235 · Cited by 18 · see citing works
Characterization of female germline stem cells from adult mouse ovaries and the role of rapamycin on them
Yang, H., Yao, X., Tang, F., Wei, Y., Hua, J., & Peng, S. (2018) · Cytotechnology · doi:10.1007/s10616-018-0196-6 · Cited by 18 · see citing works
High-Throughput Sequencing Reveals Circulating miRNAs as Potential Biomarkers for Measuring Puberty Onset in Chicken (Gallus gallus)
Han, W., YunFen, Z., Su, Y., Li, G., Qu, L., Zhang, H., Wang, K., Zou, J., & Liu, H. (2016) · PLoS ONE · doi:10.1371/journal.pone.0154958 · Cited by 15 · see citing works
“mTOR signaling pathway is found to couple the nutritional status to regulate puberty onset in rats [39].”
Background
Possible role of the leptin system in controlling puberty in the male chub mackerel, Scomber japonicus
Ohga, H., Hirata, D., Matsumori, K., Kitano, H., Nagano, N., Yamaguchi, A., & Matsuyama, M. (2016) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2016.09.009 · Cited by 16 · see citing works
High-Throughput Sequencing Reveals Hypothalamic MicroRNAs as Novel Partners Involved in Timing the Rapid Development of Chicken (Gallus gallus) Gonads
Han, W., Zou, J., Wang, K., Su, Y., YunFen, Z., Song, C. W., Li, G., Qu, L., Zhang, H., & Liu, H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129738 · Cited by 16 · see citing works
“In addition, prominent among the KEGG pathways, mammalian target of rapamycin (mTOR) signaling pathway has been found to couple the nutritional status to regulate puberty onset in rats [59] and the timing of molt inManduca sexta [60].”
Background
Proteomic analysis of hypothalamus in prepubertal and pubertal female goat
Ye, J., Yan, X., Qin, P., Gong, X., Li, H., Liu, Y., Yu, T., Zhang, Y., Ling, Y., Cao, H., et al. (2021) · Journal of Proteomics · doi:10.1016/j.jprot.2021.104411 · Cited by 13 · see citing works
Kisspeptins in human reproduction—future therapeutic potential
Kaur, K. K., Allahbadia, G. N., & Singh, M. (2012) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-012-9856-1 · Cited by 13 · see citing works
Emerging roles of lipid and metabolic sensing in the neuroendocrine control of body weight and reproduction
Rodríguez-Vázquez, E., Torrecillas, Á. A., López-Sancho, M., Castellano, J. M., & Tena‐Sempere, M. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1454874 · Cited by 11 · see citing works
The hippo pathway: a molecular bridge between environmental cues and pace of life
Ahi, E. P., Panda, B., & Primmer, C. R. (2025) · BMC Ecology and Evolution · doi:10.1186/s12862-025-02378-8 · Cited by 12 · see citing works
MiR-199-3p modulates the onset of puberty in rodents probably by regulating the expression of Kiss1 via the p38 MAPK pathway
Li, X., Xiao, J., Li, K., & Zhou, Y. (2020) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2020.110994 · Cited by 11 · see citing works
Linking Nutrition, Maturation and Aging: From Thrifty Genes to the Spendthrift Phenotype
Stipp, D. (2011) · Aging · doi:10.18632/aging.100286 · Cited by 11 · see citing works
“This network is also thought to involve AMPK (AMP-activated protein kinase), another pivotal nutrition sensor known to interact with mTOR [63].”
Background
Developing Novel Experimental Models of m-TORopathic Epilepsy and Related Neuropathologies: Translational Insights from Zebrafish
de Abreu, M. S., Demin, K. A., Kotova, M. M., Mirzaei, F., Shariff, S., Kantawala, B., Zakharchenko, K. V., Kolesnikova, T. O., Dilbaryan, K., Grigoryan, A., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021530 · Cited by 10 · see citing works
“Finally, the initiation of puberty and the gonadotropic axis are both regulated by centrally expressed mTOR [30].”
Background
AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin
Vazquez, M. J., Novelle, M. G., Rodríguez‐Pacheco, F., Lage, R., Varela, L., López, M., Pinilla, L., Tena‐Sempere, M., & Diéguez, C. (2020) · Cells · doi:10.3390/cells9091940 · Cited by 9 · see citing works
“In addition, ghrelin has been shown to activate hypothalamic mTOR signaling, while inactivation of central mTOR by rapamycin attenuated ghrelin’s orexigenic effect [15], and caused inhibition of the gonadotropic axis and puberty; this period is one of the major determinants of GH secretory status [19,20].”
Background
Stimulation of GHRH Neuron Axon Growth by Leptin and Impact of Nutrition during Suckling in Mice
Decourtye, L., Clemessy, M., Leneuve, P., Mire, E., Ledent, T., Bouc, Y. L., & Kappeler, L. (2023) · Nutrients · doi:10.3390/nu15051077 · Cited by 8 · see citing works
“Leptin has been reported to act on different neuronal populations, including the NPY neurons of the arcuate nucleus to control metabolism, and the ventral premammillary nucleus neurons to generate a permissive signal for reproduction [14,23,24].”
Background
Mechanisms linking energy balance and reproduction: impact of prenatal environment
Keen‐Rhinehart, E. (2016) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2016-0004 · Cited by 7 · see citing works
“It is likely that the central inhibition of mTOR nullifies the action of leptin on the HPG axis via changes in kisspeptin because pharmacological blockade of mTOR also significantly decreases kisspeptin expression in the Arc and AVPV in rats [89].”
Background
Increased Prepubertal Body Weight Enhances Leptin Sensitivity in Proopiomelanocortin and Neuropeptide Y Neurons Before Puberty Onset in Female Rats
Castro-González, D., Fuente-Martín, E., Sanchez-Garrido, M. A., Argente-Arizón, P., Tena‐Sempere, M., Barrios, V., Chowen, J. A., & Argente, J. (2015) · Endocrinology · doi:10.1210/en.2014-1759 · Cited by 7 · see citing works
p53 Mediates GnRH Secretion via Lin28/let-7 System in GT1-7 Cells
Chen, T., Wu, H., Chen, X., Xie, R., Wang, F., Sun, H., & Chen, L. (2020) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s279901 · Cited by 7 · see citing works
Analysis of protein phosphorylation sites in the hypothalamus tissues of pubescent goats
Yan, X., Gong, X., Lin, T., Lin, M., Qin, P., Ye, J., Li, H., Hong, Q., Li, M., Liu, Y., et al. (2022) · Journal of Proteomics · doi:10.1016/j.jprot.2022.104574 · Cited by 7 · see citing works
Transcriptome analysis reveals miRNA expression profiles in hypothalamus tissues during the sexual development of Jining grey goats
Li, Q., Chao, T., Wang, Y., Xuan, R., Guo, Y., He, P., Zhang, L., & Wang, J. (2024) · BMC Genomics · doi:10.1186/s12864-024-10735-y · Cited by 6 · see citing works
“ANXA7 is also involved in glucose metabolism by regulating insulin secretion [49, 51], and energy reserve levels and metabolic status plays important roles in the sexual maturation of female animals [52].”
Background
Interplay of KNDy and nNOS neurons: A new possible mechanism of GnRH secretion in the adult brain
Prashar, V., Arora, T., Singh, R., Sharma, A., & Parkash, J. (2021) · Reproductive Biology · doi:10.1016/j.repbio.2021.100558 · Cited by 6 · see citing works
What’s Genetic Variation Got to Do with It? Starvation-Induced Self-Fertilization Enhances Survival in Paramecium
Thind, A. S., Vitali, V., Guarracino, M. R., & Catania, F. (2020) · Genome Biology and Evolution · doi:10.1093/gbe/evaa052 · Cited by 6 · see citing works
Muricholic acid mediates puberty initiation via the hypothalamic TGR5 signaling pathway
Wang, S., Huang, K., Liu, A., Wang, S., Jiang, R., Chen, W., Wang, H., Ullah, R., Xue, C., Wu, W., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2511404122 · Cited by 5 · see citing works
“Recent evidence has indicated that the mTOR signaling pathway, specifically mTORC1, within hypothalamic neuronal populations, plays a crucial role in controlling puberty onset ( 52 ).”
A disputed evidence on obesity: comparison of the effects of Rcan2−/− and Rps6kb1−/− mutations on growth and body weight in C57BL/6J mice
Zhao, J., Li, S.-W., Gong, Q.-Q., Ding, L., Jin, Y.-C., Zhang, J., Gao, J.-G., & Sun, X.-Y. (2016) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1600276 · Cited by 5 · see citing works
Transcriptome analysis revealed the characteristics and functions of long non-coding RNAs in the hypothalamus during sexual maturation in goats
Li, Q., Chao, T., Wang, Y., Xuan, R., Guo, Y., He, P., Zhang, L., & Wang, J. (2024) · Frontiers in Veterinary Science · doi:10.3389/fvets.2024.1404681 · Cited by 4 · see citing works
“In mammals, LEP acts on neural circuits in the hypothalamus to regulate feeding and energy metabolism (44), and in addition, leptin can be involved in the regulation of puberty through mTOR (9). qRT-PCR verification of lncRNA expression levels in hypothalamus at four developmental stages of Jining…”
Background
Kisspeptin-10 Administration Regulates mTOR and AKT Activities and Oxidative Stress in Mouse Cardiac Tissue
Akkaya, H. (2021) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s0022093021020095 · Cited by 3 · see citing works
lncRNA Sequencing of Antler Mesenchymal Tissue Revealed that the Regulatory Network of Antler Cell Proliferation and Differentiation
Han, R., Han, L., Xia, Y., Guo, M., & Li, H. (2021) · Animal Biotechnology · doi:10.1080/10495398.2021.1924762 · Cited by 3 · see citing works
“The PI3K/AKT signaling pathway can promote a large number of blood vessels to meet nutrient supply by activating the downstream of the mTOR signaling pathway.(42,43) The lncRNAs that interact with these genes may play a unique role in the MP of the antler growth (TCONS_00087144, TCONS_00072627, and TCONS_00007422).”
Background
Β-endorphin-immunoreactive perikarya appear to receive innervation from NPY-immunoreactive fiber varicosities in the human hypothalamus
Dudás, B., & Merchenthaler, I. J. (2021) · Brain Structure and Function · doi:10.1007/s00429-021-02416-3 · Cited by 3 · see citing works
O neuropeptídeo kisspeptina e a reprodução animal: uma revisão
Dias, J. C. O., Veloso, C. M., Donzele, R. F. M. D. O., & de Carvalho, G. R. (2018) · Multi-Science Journal · doi:10.33837/msj.v1i2.76 · Cited by 2 · see citing works
Creatine Acts as a Mediator of the Causal Effect of Obesity on Puberty Onset in Girls: Evidence from Mediation Mendelian Randomization Study
Jin, C., & Zhao, G. (2024) · Metabolites · doi:10.3390/metabo14030137 · Cited by 4 · see citing works
“…onset and partially reversing the undernutrition-induced reduction in gonadotropin levels and puberty [35,59], while inhibiting mTOR activity delays puberty onset by reducing Kiss1 gene expression in the arcuate nucleus and lowering the circulating levels of LH and estradiol in female rats [35,59].”
Background
Pathogenesis of ovarian dysfunction in women with diabetes mellitus 1 type
Tolpygina, M. G., Ивановна, А. Е., Borovik, N. V., & Tiselko, A. V. (2018) · Journal of obstetrics and women s diseases · doi:10.17816/jowd6715-12 · Cited by 1 · see citing works
MiR-505-3p, a New Repressor of Puberty Onset in Female MicePreprint
Li, T., Wang, M., Zhou, Y., Li, Y., Chen, L., Xu, F., Li, K., & Xiao, J. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/271718 · Cited by 1 · see citing works
Neuroendocrine Disruption of Reproduction
Fudvoye, J., Bourguignon, J.-P., & Parent, A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.65356-4 · Cited by 1 · see citing works
Control hormonal de la homeostásis energética: de la célula al cerebro
Osorio-Paz, I., & Sacanelles, R. S. (2012) · REB. Revista de educación bioquímica
Efecto de la sobrenutrición neonatal en la respuesta aguda a la leptina en los periodos prepuberal y peripuberal
González, D. (2014) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Gonadotropin-Dependent Precocious Puberty; Female and Male
Mul, D., Oostdijk, W., & Drop, S. L. S. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.03912-x
Ghrelin, Lipid Metabolism, and Metabolic Syndrome
de Morentin, P. B. M., Tovar, S. A., Nogueiras, R., López, M., & Diéguez, C. (2013) · doi:10.1002/9781118395318.ch29
Neuroendocrine and Molecular Mechanisms for the Metabolic Control of Puberty: Recent Developments
Tena‐Sempere, M. (2014) · Research and perspectives in endocrine interactions · doi:10.1007/978-3-319-09168-6_9
ESTUDO DE VIA DE PI3K EM MELANOMAS DE CORÓIDE
Freeman, G. M. (2012)
Neuroendocrine Disruption of Reproduction
Fudvoye, J., Bourguignon, J.-P., & Parent, A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.11074-8
Metabolic regulation of female puberty via hypothalamic AMPK-kisspeptin signaling
Roa, J., Barroso, A., Ruíz-Pino, F., Vazquez, M. J., Seoane‐Collazo, P., Martínez‐Sánchez, N., García-Galiano, D., İlhan, T., Pineda, R., León, S., et al. (2019) · Yearbook of pediatric endocrinology · doi:10.1530/ey.16.7.3

The Mammalian Target of Rapamycin as Novel Central Regulator of Puberty Onset via Modulation of Hypothalamic Kiss1 System
Roa, J., García-Galiano, D., Varela, L., Sanchez-Garrido, M. A., Pineda, R., Castellano, J. M., Ruíz-Pino, F., Romero, M., Aguilar, E., López, M., et al. (2009) · Endocrinology · doi:10.1210/en.2009-0096 · Cited by 247 · see citing works
Mechanisms for the metabolic control of puberty
Rodríguez-Vázquez, E., Tena‐Sempere, M., & Castellano, J. M. (2020) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2020.06.003 · Cited by 6 · see citing works
Metabolic control of puberty onset: New players, new mechanisms
Roa, J., García-Galiano, D., Castellano, J. M., Gaytán, F., Pinilla, L., & Tena‐Sempere, M. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.12.018 · Cited by 174 · see citing works
Neuroendocrine Mechanisms for the Metabolic Control of Puberty.
Tena‐Sempere, M. (2011) · Biology of Reproduction · doi:10.1093/biolreprod/85.s1.19
Metabolic control of female puberty: potential therapeutic targets
Castellano, J. M., & Tena‐Sempere, M. (2016) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2016.1212015 · Cited by 65 · see citing works

Authors: Roa, J., & Tena-Sempere, M.
Affiliations: University of Córdoba (ES)
ORCID: Roa, Juan
Venue: Trends in Endocrinology & Metabolism
Publisher: Elsevier BV
Published: 2010-09
Volume: 21
Issue: 9
Pages: 519-528
ISSN: 1043-2760 (ISSN-L)
DOI: 10.1016/j.tem.2010.05.003
OpenAlex: W2134113504
Cited by: 106
References: 74
Citations by year: 2026: 1 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 10 · 2020: 9 · 2019: 9 · 2018: 14 · 2017: 4 · 2016: 9 · 2015: 9 · 2014: 4 · 2013: 5 · 2012: 13
FWCI: 1.22
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Endocrinology and Metabolism (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords: puberty onset, mTOR signaling, leptin, hypothalamus, energy homeostasis, CRTC1, kisspeptin, energy balance, reproductive development
MeSH terms: Animals, Energy Metabolism, Humans, Puberty, Signal Transduction, Leptin, TOR Serine-Threonine Kinases

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Energy balance and puberty onset: Emerging role of central mTOR signaling

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