Somatostatin is required for masculinization of growth hormone-regulated hepatic gene expression but not of somatic growth.
Open accessAbstract
Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst(-/-)) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst(-/-) compared with Smst(+/+) mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst(-/-) mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst(-/-) mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Somatostatin and Its Receptor Family
Patel, Y. (1999) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1999.0183 · Cited by 1,648 · see citing works
Self-citationTeglund, S., McKay, C., Schuetz, E. G., van Deursen, J. M., Stravopodis, D. J., Wang, D., Brown, M. P., Bodner, S. M., Grosveld, G. C., & Ihle, J. N. (1998) · Cell · doi:10.1016/s0092-8674(00)81444-0 · Cited by 1,266 · see citing works
Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression
Udy, G. B., Towers, R. P., Snell, R. G., Wilkins, R. J., Park, S.-H., Ram, P. A., Waxman, D. J., & Davey, H. W. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7239 · Cited by 986 · see citing works
Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse.Preprint
Ormandy, C. J., Camus, A., Barra, J., Damotte, D., Lucas, B., Buteau, H., Edery, M., Brousse, N., Babinet, C., Binart, N., et al. (1997) · Genes & Development · doi:10.1101/gad.11.2.167 · Cited by 806 · see citing works
Sexual Dimorphism in the Control of Growth Hormone Secretion*
Jansson, J., Edén, S., & Isaksson, O. G. P. (1985) · Endocrine Reviews · doi:10.1210/edrv-6-2-128 · Cited by 745 · see citing works
Plotsky, P. M., & Vale, W. (1985) · Science · doi:10.1126/science.2864742 · Cited by 540 · see citing works
Kelly, M. A., Rubinstein, M., Asa, S. L., Zhang, G., Sáez, C., Bunzow, J. R., Allen, R. G., Hnasko, R. M., Ben‐Jonathan, N., Grandy, D. K., et al. (1997) · Neuron · doi:10.1016/s0896-6273(00)80351-7 · Cited by 425 · see citing works
Self-citationWaxman, D. J., Pampori, N. A., Ram, P. A., Agrawal, A. K., & Shapiro, B. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.15.6868 · Cited by 251 · see citing works
Regulatory mechanisms of growth hormone secretion are sexually dimorphic.
Jaffe, C. A., Ocampo-Lim, B., Guo, W., Krueger, K., Sugahara, I., DeMott-Friberg, R., Bermann, M., & Barkan, A. L. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2908 · Cited by 236 · see citing works
Secretory rhythm of growth hormone regulates sexual differentiation of mouse liver
Norstedt, G., & Palmiter, R. D. (1984) · Cell · doi:10.1016/0092-8674(84)90030-8 · Cited by 231 · see citing works
Asa, S. L., Kelly, M. A., Grandy, D. K., & Low, M. J. (1999) · Endocrinology · doi:10.1210/endo.140.11.7118 · Cited by 178 · see citing works
Self-citationSex differences in the ultradian pattern of plasma growth hormone concentrations in mice
MacLeod, J. N., Pampori, N. A., & Shapiro, B. (1991) · Journal of Endocrinology · doi:10.1677/joe.0.1310395 · Cited by 173 · see citing works
Zheng, H., Bailey, A., Jiang, M.-H., Honda, K., Chen, H. Y., Trumbauer, M. E., Van der Ploeg, L. H. T., Schaeffer, J. M., Leng, G., & Smith, R. G. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.11.0016 · Cited by 169 · see citing works
Distinctive Roles of STAT5a and STAT5b in Sexual Dimorphism of Hepatic P450 Gene Expression
Park, S.-H., Liu, X., Hennighausen, L. G., Davey, H. W., & Waxman, D. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.11.7421 · Cited by 152 · see citing works
Thorner, M. O., Frohman, L. A., Leong, D. A., et al. (1984) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-59-5-846 · Cited by 146 · see citing works
Kumar, U., Laird, D. W., Srikant, C. B., et al. (1997) · Endocrinology · doi:10.1210/endo.138.10.5566 · Cited by 123 · see citing works
Self-citationSex-specific, growth hormone-regulated transcription of the cytochrome P450 2C11 and 2C12 genes.
Sundseth, S. S., Alberta, J. A., & Waxman, D. J. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50612-3 · Cited by 115 · see citing works
Chowen, J. A., Steiner, R. A., & Clifton, D. K. (1989) · Endocrinology · doi:10.1210/endo-125-1-357 · Cited by 113 · see citing works
Low, M. J., Hammer, R. E., Goodman, R. H., et al. (1985) · Cell · doi:10.1016/0092-8674(85)90075-3 · Cited by 110 · see citing works
Self-citationPAINSON, J.-C., Thorner, M. O., Krieg, R. J., & Tannenbaum, G. S. (1992) · Endocrinology · doi:10.1210/endo.130.1.1345780 · Cited by 103 · see citing works
STAT5b-deficient Mice Are Growth Hormone Pulse-resistant
Davey, H. W., Park, S.-H., Grattan, D. R., McLachlan, M. J., & Waxman, D. J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.50.35331 · Cited by 101 · see citing works
STAT5 Signaling in Sexually Dimorphic Gene Expression and Growth Patterns
Davey, H. W., Wilkins, R. J., & Waxman, D. J. (1999) · The American Journal of Human Genetics · doi:10.1086/302599 · Cited by 98 · see citing works
Somatostatin receptor subtype 1 modulates basal inhibition of growth hormone release in somatotrophs
Kreienkamp, H., Akgün, E., Baumeister, H., Meyerhof, W., & Richter, D. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01582-3 · Cited by 94 · see citing works
Hormonal Regulation of Liver Cytochrome P450 Enzymes
Waxman, D. J., & Chang, T. K. H. (2015) · Springer eBooks · doi:10.1007/978-3-319-12108-6_11 · Cited by 78 · see citing works
A New Orphan Receptor Involved in Pulsatile Growth Hormone Release
Smith, R. G., Feighner, S. D., Prendergast, K., Guan, X.-M., & Howard, A. (1999) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(98)00132-5 · Cited by 72 · see citing works
Kimura, N., Tomizawa, S., Arai, K. N., & Kimura, N. (1998) · Endocrinology · doi:10.1210/endo.139.4.5952 · Cited by 68 · see citing works
Lechan, R. M., Goodman, R. H., Rosenblatt, M., et al. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.9.2780 · Cited by 65 · see citing works
Sueyoshi, T., Yokomori, N., Korach, K. S., & Negishi, M. (1999) · Molecular Pharmacology · doi:10.1124/mol.56.3.473 · Cited by 64 · see citing works
Wagner, C., Caplan, S. R., & Tannenbaum, G. S. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.275.6.e1046 · Cited by 53 · see citing works
Differential regulation of somatostatin receptor types 1–5 in rat aorta after angioplasty
Khare, S., Kumar, U., Sasi, R., et al. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.2.387 · Cited by 44 · see citing works
Self-citationKovács, M., Kineman, R. D., Schally, A. V., et al. (1997) · Endocrinology · doi:10.1210/endo.138.11.5498 · Cited by 42 · see citing works
Zhang, Beaudet, & Tannenbaum (1999) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1999.00295.x · Cited by 41 · see citing works
Nurhidayat, N., Tsukamoto, Y., Sigit, K., & Sasaki, F. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01081-1 · Cited by 35 · see citing works
PAINSON, J.-C., Veldhuis, J. D., & Tannenbaum, G. S. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.278.5.e933 · Cited by 35 · see citing works
Gonadal regulation of somatostatin receptor 1, 2 and 3 mRNA levels in the rat anterior pituitary
Señarís, R. M., Lago, F., & Diéguez, C. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(96)00042-3 · Cited by 34 · see citing works
Murray, Simonian, Herbison, A. E., & Gillies (1999) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1999.00286.x · Cited by 30 · see citing works
Rubinstein, M., Japón, M. Á., & Low, M. J. (1993) · Nucleic Acids Research · doi:10.1093/nar/21.11.2613 · Cited by 24 · see citing works
Self-citationGrowth hormone-releasing hormone peptide and mRNA are overexpressed in GH-deficient Ames dwarf mice.
Phelps, C., Dalçik, H., Endo, H., et al. (1993) · Endocrinology · doi:10.1210/endo.133.6.7694848 · Cited by 21 · see citing works
McIntosh, I., & Bishop, J. O. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.5.2202 · Cited by 16 · see citing works
Murray, Simonian, Herbison, A. E., & Gillies (1999) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1999.00287.x · Cited by 14 · see citing works
Characterization and regulation of sex-specific mouse steroid hydroxylase genes
Yoshioka, H., Lindberg, R. L. P., Wong, G., et al. (1990) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y90-116 · Cited by 12 · see citing works
McIntosh, I., & Bishop, J. O. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.5.2202-2207.1989 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hauge-Evans, A. C., King, A. J., Carmignac, D., Richardson, C. C., Robinson, I. C. A. F., Low, M. J., Christie, M. R., Persaud, S. J., & Jones, P. M. (2009) · Diabetes · doi:10.2337/db08-0792 · Cited by 335 · see citing works
Self-citationSustained alterations of hypothalamic tanycytes during posttraumatic hypopituitarism in male mice
Osterstock, G., El Yandouzi, T., Romanò, N., Carmignac, D., Langlet, F., Coutry, N., Guillou, A., Schaeffer, M., Chauvet, N., Vanacker, C., et al. (2014) · Endocrinology · doi:10.1210/en.2013-1336 · Cited by 43 · see citing works
Kok, P., Paulo, R. C., Cosma, M., Mielke, K. L., Miles, J. M., Bowers, C. Y., & Veldhuis, J. D. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0522 · Cited by 35 · see citing works
Sex-steroid control of the aging somatotropic axis
Veldhuis, J. D., Erickson, D., Iranmanesh, A., Miles, J. M., & Bowers, C. Y. (2005) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2005.07.006 · Cited by 30 · see citing works
Erickson, D., Keenan, D. M., Farhy, L., Mielke, K., Bowers, C. Y., & Veldhuis, J. D. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1621 · Cited by 21 · see citing works
Iranmanesh, A., Bowers, C. Y., & Veldhuis, J. D. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0205 · Cited by 10 · see citing works
- Authors
- Low, M. J., Otero-Corchon, V., Parlow, A. F., Ramirez, J. L., Kumar, U., Patel, Y. C., & Rubinstein, M.
- Affiliations
- Oregon Health & Science University (US)
- University of California, Los Angeles (US)
- Royal Victoria Hospital (CA)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Corresponding author
- Low, Malcolm J.
- Venue
- Journal of Clinical Investigation
- Published
- 2001-06-15
- Volume
- 107
- Issue
- 12
- Pages
- 1571-1580
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC200191
- OpenAlex
- W1981736657
- Semantic Scholar
- a8ccce5edfe93961325a0f21fb46ee06d0e5bd16
- Cited by
- 163
- References
- 42
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 4 · 2019: 6 · 2018: 6 · 2017: 3 · 2016: 4 · 2015: 9 · 2014: 9 · 2013: 8 · 2012: 2
- FWCI
- 6.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (submittedVersion, cc-by-nc-sa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- Funders
- Robert Wood Johnson Foundation
- National Institutes of Health (5r01ns032160-06)
- Canadian Institutes of Health Research
- National Institute of Neurological Disorders and Stroke (NS32160)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Keywords
- somatostatin, growth hormone secretion, sex differences, masculinization, hepatic gene expression, cytochrome P450, somatostatin receptors, hypothalamus, pituitary gland, physical growth, ultradian rhythms
- MeSH terms
- Animals, Body Weight, Female, Genotype, Hypothalamus, Liver, Male, Pituitary Gland, Recombination, Genetic, RNA, Messenger, Sex Characteristics, Somatostatin, Growth Hormone, Transcription, Genetic, Receptors, Somatostatin, Mice, Knockout, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review