Assessment of Growth Parameters and Life Span of GHR/BP Gene-Disrupted Mice 1
Abstract
GH has many biological roles, including promotion of growth. Most, if not all, of its roles are achieved through interaction with its receptor. We chose to study the effects of loss of GH signaling on growth and aging in a mouse model for Laron Syndrome (LS) in which the GHR/BP gene has been disrupted. We observed that mice homozygous for the disruption (-/-) were significantly smaller than normal wild-type (+/+) mice as well as mice heterozygous for the disruption, even at 1.5 yr of age. IGF-I levels were also significantly lower in the -/- mice and remained low as the mice aged. IGFBP-3 levels were severely reduced in the -/- mice, whereas IGFBP-1, -2, and -4 levels remained unchanged. Finally, the -/- mice lived significantly longer than +/+ and +/- mice. The latter result contradicts the anti-aging GH data and suggests the need for further analysis of GH and aging.
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Mutations that decrease IGF1 levels or activity cause reduced growth and longer life in mice by up to 65%.
“Mutations that decrease IGF1 levels or activity cause reduced growth and longer life in mice by up to 65% (Coschigano et al., 2000; Holzenberger et al., 2003).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Coschigano et al., 2000
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Cites
Kimura, K. D., Tissenbaum, H. A., Liu, Y., & Ruvkun, G. (1997) · Science · doi:10.1126/science.277.5328.942 · Cited by 2,250 · see citing works
Daughaday, W. H., & Rotwein, P. S. (1989) · Endocrine Reviews · doi:10.1210/edrv-10-1-68 · Cited by 1,718 · see citing works
The p66shc adaptor protein controls oxidative stress response and life span in mammals
Migliaccio, E., Giorgio, M., Mele, S., Pelicci, G., Reboldi, P., Pandolfi, P. P., Lanfrancone, L., & Pelicci, P. G. (1999) · Nature · doi:10.1038/46311 · Cited by 1,712 · see citing works
Hossenlopp, P., Seurin, D., Segovia, B., Hardouin, S., & Binoux, M. (1986) · Analytical Biochemistry · doi:10.1016/0003-2697(86)90507-5 · Cited by 1,143 · see citing works
Cunningham, B. C., Ultsch, M. H., de Vos, A. M., Mulkerrin, M. G., Clauser, K. R., & Wells, J. A. (1991) · Science · doi:10.1126/science.1948064 · Cited by 873 · see citing works
Zhou, Y., Xu, B. C., Maheshwari, H., He, L., Reed, M. A., Lozykowski, M. G., Okada, S., Cataldo, L. R., Coschigamo, K., Wagner, T. E., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13215 · Cited by 802 · see citing works
Self-citationGodowski, P. J., Leung, D. W., Meacham, L. R., GALGANI, J. P., Hellmiss, R., Keret, R., Rotwein, P. S., Parks, J. S., Laron, Z., & Wood, W. I. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.20.8083 · Cited by 604 · see citing works
Mechanism of the Stimulatory Effect of Growth Hormone on Longitudinal Bone Growth*
Isaksson, O. G. P., Lindahl, A. H., NILSSON, A., & Isgaard, J. (1987) · Endocrine Reviews · doi:10.1210/edrv-8-4-426 · Cited by 579 · see citing works
Baumbach, W. R., Horner, D. L., & Logan, J. S. (1989) · Genes & Development · doi:10.1101/gad.3.8.1199 · Cited by 399 · see citing works
Thomas, M. J., & Thomas, J. A. (1988) · Springer eBooks · doi:10.1007/978-1-4684-5499-4_13 · Cited by 298 · see citing works
Mechanism of signaling by growth hormone receptor
Argetsinger, L. S., & Carter‐Su, C. (1996) · Physiological Reviews · doi:10.1152/physrev.1996.76.4.1089 · Cited by 271 · see citing works
The Growth Hormone/Prolactin Receptor Family
Kelly, P. A., Ali, S., Rozakis, M., Goujon, L., Nagano, M. C., Pellegrini, I., GOULD, D., Djiane, J., Edery, M., Finidori, J., et al. (1993) · Elsevier eBooks · doi:10.1016/b978-0-12-571148-7.50009-9 · Cited by 222 · see citing works
Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice.
Chen, W. Y., Wight, D. C., Wagner, T. E., & Kopchick, J. J. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.13.5061 · Cited by 198 · see citing works
Self-citationDonahue, L. R., & Beamer, W. G. (1993) · Journal of Endocrinology · doi:10.1677/joe.0.1360091 · Cited by 169 · see citing works
Glycine 119 of Bovine Growth Hormone is Critical for Growth-Promoting Activity
Chen, W. Y., Wight, D. C., Mehta, B. V., Wagner, T. E., & Kopchick, J. J. (1991) · Molecular Endocrinology · doi:10.1210/mend-5-12-1845 · Cited by 165 · see citing works
Self-citationPituitary and Testicular Function in Growth Hormone Receptor Gene Knockout Mice
Chandrashekar, V., Bartke, A., Coschigano, K. T., & Kopchick, J. J. (1999) · Endocrinology · doi:10.1210/endo.140.3.6557 · Cited by 163 · see citing works
Self-citationChen, W. Y., White, M. E., Wagner, T. E., et al. (1991) · Endocrinology · doi:10.1210/endo-129-3-1402 · Cited by 156 · see citing works
Deficits in Female Reproductive Function in GH-R-KO Mice; Role of IGF-I
Danilovich, N., Wernsing, D. R., Coschigano, K. T., Kopchick, J. J., & Bartke, A. (1999) · Endocrinology · doi:10.1210/endo.140.6.6992 · Cited by 156 · see citing works
Self-citationIn vitro and in vivo studies of antagonistic effects of human growth hormone analogs.
Chen, W. Y., Chen, N. Y., Yun, J., et al. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40764-2 · Cited by 147 · see citing works
Sotiropoulos, A., Goujon, L., Simonin, G., et al. (1993) · Endocrinology · doi:10.1210/endo.132.4.8462483 · Cited by 145 · see citing works
Does growth hormone prevent or accelerate aging?
Bartke, A., Brown‐Borg, H. M., Bode, A. M., Carlson, J. C., Hunter, W. S., & Bronson, R. T. (1998) · Experimental Gerontology · doi:10.1016/s0531-5565(98)00032-1 · Cited by 120 · see citing works
TRANSGENIC MODELS OF GROWTH HORMONE ACTION
Kopchick, J. J., Bellush, L. L., & Coschigano, K. T. (1999) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.19.1.437 · Cited by 117 · see citing works
Self-citationThe "Little People" of the Island of Krk - Revisited. Etiology of Hypopituitarism Revealed
Kržišnik, C., Kolacio, Z., Battelino, T., Brown, M., Parks, J. S., & Laron, Z. (1999) · International Journal on Disability and Human Development · doi:10.1515/ijdhd.1999.1.1.9 · Cited by 116 · see citing works
Effects of streptozotocin treatment in growth hormone (GH) and GH antagonist transgenic mice
Chen, N. Y., Chen, W. Y., Bellush, L. L., Yang, C., Striker, L. J., Striker, G. E., & Kopchick, J. J. (1995) · Endocrinology · doi:10.1210/endo.136.2.7835300 · Cited by 102 · see citing works
Self-citationCellular mechanisms in the processing of growth hormone and its receptor
Roupas, P., & Herington, A. C. (1989) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(89)90184-6 · Cited by 99 · see citing works
Bellush, L. L., Doublier, S., Holland, A. N., et al. (2000) · Endocrinology · doi:10.1210/endo.141.1.7284 · Cited by 84 · see citing works
Self-citationCamacho‐Hübner, C., Clemmons, D. R., & D’Ercole, A. J. (1991) · Endocrinology · doi:10.1210/endo-129-3-1201 · Cited by 80 · see citing works
Self-citationThirone, A. C. P., Carvalho, C. R. D. O., & Saad, M. J. A. (1999) · Endocrinology · doi:10.1210/endo.140.1.6417 · Cited by 63 · see citing works
Growth Hormone Binding Proteins and Various Forms of Growth Hormone: Implications for Measurements
BAUMANN, G. (1990) · Acta Paediatrica · doi:10.1111/j.1651-2227.1990.tb11677.x · Cited by 52 · see citing works
Growth Hormone Receptors ‐ their Structure, Location and Role
Waters, M. J., Barnard, R. T., Lobie, P., et al. (1990) · Acta Paediatrica · doi:10.1111/j.1651-2227.1990.tb11600.x · Cited by 48 · see citing works
Edens, A., Southard, J. N., & Talamantes, F. J. (1994) · Endocrinology · doi:10.1210/endo.135.6.7988474 · Cited by 43 · see citing works
Insulin Exposure and Aging Theory
Parr, T. B. (2009) · Gerontology · doi:10.1159/000213848 · Cited by 40 · see citing works
The GH Receptor and Signal Transduction
Kelly, P. A., Goujon, L., Sotiropoulos, A., et al. (2008) · Hormone Research · doi:10.1159/000184185 · Cited by 39 · see citing works
Does the serum binding protein for growth hormone have a functional role?
Herington, A. C., Ymer, S. I., & Tiong, T. S. (1991) · PubMed · Cited by 20 · see citing works
The Growth Hormone Receptor and Growth Hormone-Binding Protein: Structure, Functions, and Regulation
Cramer, S. D., & Talamantes, F. J. (1993) · Elsevier eBooks · doi:10.1016/b978-0-12-629055-4.50009-x · Cited by 8 · see citing works
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IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P. C., Cervera, P., & Le Bouc, Y. (2003) · Nature · doi:10.1038/nature01298 · Cited by 2,109 · see citing works
Ink4a/Arf expression is a biomarker of aging
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22475 · Cited by 1,486 · see citing works
Extension of Chronological Life Span in Yeast by Decreased TOR Pathway Signaling
Powers, R. W., Kaeberlein, M., Caldwell, S. D., Kennedy, B. K., & Fields, S. (2006) · Genes & Development · doi:10.1101/gad.1381406 · Cited by 982 · see citing works
Body size, energy metabolism and lifespan
Speakman, J. R. (2005) · Journal of Experimental Biology · doi:10.1242/jeb.01556 · Cited by 914 · see citing works
Molecular mechanisms of dietary restriction promoting health and longevity
Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714 · see citing works
The GH/IGF-1 axis in ageing and longevity
Junnila, R. K., List, E. O., Berryman, D. E., Murrey, J. W., & Kopchick, J. J. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.67 · Cited by 574 · see citing works
Self-citationSelman, C., Lingard, S., Choudhury, A. I., Batterham, R. L., Claret, M., Clements, M., Ramadani, F., Okkenhaug, K., Schuster, E., Blanc, E., et al. (2008) · The FASEB Journal · doi:10.1096/fj.07-9261com · Cited by 532 · see citing works
Coschigano, K. T., Holland, A. N., Riders, M. E., List, E. O., Flyvbjerg, A., & Kopchick, J. J. (2003) · Endocrinology · doi:10.1210/en.2003-0374 · Cited by 510 · see citing works
Self-citationBarbieri, M., Bonafè, M., Franceschi, C., & Paolisso, G. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00296.2003 · Cited by 456 · see citing works
Finch, C. E., & Ruvkun, G. (2001) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.2.1.435 · Cited by 446 · see citing works
Extending the Lifespan of Long-Lived Mice
Bartke, A., Wright, J. C., Mattison, J. A., Ingram, D. K., Miller, R. A., & Roth, G. S. (2001) · Nature · doi:10.1038/35106646 · Cited by 422 · see citing works
The starvation hormone, fibroblast growth factor-21, extends lifespan in mice
Zhang, Y., Xie, Y., Berglund, E. D., Coate, K. C., He, T. T., Katafuchi, T., Xiao, G., Potthoff, M. J., Wei, W., Wan, Y., et al. (2012) · eLife · doi:10.7554/elife.00065 · Cited by 420 · see citing works
Calorie restriction and cancer prevention: metabolic and molecular mechanisms
Longo, V. D., & Fontana, L. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2009.11.004 · Cited by 378 · see citing works
DNA damage and ageing: new-age ideas for an age-old problem
Garinis, G. A., van der Horst, G. T. J., Vijg, J., & H.J. Hoeijmakers, J. (2008) · Nature Cell Biology · doi:10.1038/ncb1108-1241 · Cited by 366 · see citing works
Endocrine regulation of ageing
Russell, S. J., & Kahn, C. R. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2234 · Cited by 356 · see citing works
The Search for Antiaging Interventions: From Elixirs to Fasting Regimens
de Cabo, R., Carmona-Gutierrez, D., Bernier, M., Hall, M. N., & Madeo, F. (2014) · Cell · doi:10.1016/j.cell.2014.05.031 · Cited by 345 · see citing works
Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1
LeRoith, D., & Yakar, S. (2007) · Nature Clinical Practice Endocrinology & Metabolism · doi:10.1038/ncpendmet0427 · Cited by 344 · see citing works
Dehkhoda, F., Lee, C. M. M., Medina, J., & Brooks, A. J. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00035 · Cited by 304 · see citing works
Calorie restriction and prevention of age‐associated chronic disease
Omodei, D., & Fontana, L. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.03.015 · Cited by 293 · see citing works
Insulin/IGF-like signalling, the central nervous system and aging
Broughton, S., & Partridge, L. (2009) · Biochemical Journal · doi:10.1042/bj20082102 · Cited by 228 · see citing works
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Gorbunova, V., Seluanov, A., & Kennedy, B. K. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.013 · Cited by 162 · see citing works
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Tyshkovskiy, A., Bozaykut, P., Borodinova, A. A., Gerashchenko, M. V., Ables, G. P., Garratt, M., Khaitovich, P., Clish, C. B., Miller, R. A., & Gladyshev, V. N. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.06.018 · Cited by 167 · see citing works
Vitale, G., Pellegrino, G., Vollery, M., & Hofland, L. J. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00027 · Cited by 166 · see citing works
The retardation of aging by caloric restriction: its significance in the transgenic era
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Tipping the metabolic scales towards increased longevity in mammals
Riera, C. E., & Dillin, A. (2015) · Nature Cell Biology · doi:10.1038/ncb3107 · Cited by 153 · see citing works
Sex- and age-specific differences in core body temperature of C57Bl/6 mice
Sanchez-Alavez, M., Alboni, S., & Conti, B. (2011) · AGE · doi:10.1007/s11357-010-9164-6 · Cited by 140 · see citing works
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Folgueras, A. R., Freitas-Rodríguez, S., Velasco, G., & López-Otín, C. (2018) · Circulation Research · doi:10.1161/circresaha.118.312204 · Cited by 113 · see citing works
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Ladiges, W., Van Remmen, H., Strong, R., Ikeno, Y., Treuting, P., Rabinovitch, P., & Richardson, A. (2009) · Aging Cell · doi:10.1111/j.1474-9726.2009.00491.x · Cited by 101 · see citing works
Anawalt, B. D., & Merriam, G. R. (2001) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70206-1 · Cited by 93 · see citing works
Ma, S., Upneja, A., Galecki, A., Tsai, Y.-M., Burant, C. F., Raskind, S., Zhang, Q., Zhang, Z. D., Seluanov, A., Gorbunova, V., et al. (2016) · eLife · doi:10.7554/elife.19130 · Cited by 89 · see citing works
The GH-IGF1 axis and longevity: the paradigm of IGF1 deficiency
Laron, Z. (2008) · HORMONES · doi:10.14310/horm.2002.1111034 · Cited by 80 · see citing works
Duran‐Ortiz, S., List, E. O., Ikeno, Y., Young, J., Basu, R., Bell, S., McHugh, T., Funk, K., Mathes, S., Qian, Y., et al. (2021) · Aging Cell · doi:10.1111/acel.13506 · Cited by 58 · see citing works
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de Magalhães, J. P. (2005) · Ageing Research Reviews · doi:10.1016/j.arr.2004.05.003 · Cited by 54 · see citing works
Expression of oxidative phosphorylation components in mitochondria of long-living Ames dwarf mice
Brown-Borg, H. M., Johnson, W. T., & Rakoczy, S. G. (2012) · AGE · doi:10.1007/s11357-011-9212-x · Cited by 52 · see citing works
Carter, C. S., Richardson, A., Huffman, D. M., & Austad, S. (2020) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glz298 · Cited by 51 · see citing works
GH Does Not Modulate the Early Fasting-Induced Release of Free Fatty Acids in Mice
Steyn, F. J., Leong, J. W., Huang, L., Tan, H. Y., Xie, T. Y., Nelson, C., Waters, M. J., Veldhuis, J. D., Epelbaum, J., & Chen, C. (2012) · Endocrinology · doi:10.1210/en.2011-1681 · Cited by 44 · see citing works
The Influence of Metformin on IGF-1 Levels in Humans: A Systematic Review and Meta-Analysis
Yang, X., Kord-Varkaneh, H., Talaei, S., Clark, C. C. T., Zanghelini, F., Tan, S. C., Zarezadeh, M., Mousavi, S. M., Rahmani, J., & Zhang, Y. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2019.104588 · Cited by 43 · see citing works
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Impairment of insulin signalling in peripheral tissue fails to extend murine lifespan
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- Authors
- Coschigano, K. T., Clemmons, D., Bellush, L. L., & Kopchick, J. J.
- Affiliations
- Ohio University (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Kopchick, John J.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2000-07
- Volume
- 141
- Issue
- 7
- Pages
- 2608-2613
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2152185756
- Cited by
- 611
- References
- 35
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 15 · 2023: 19 · 2022: 12 · 2021: 12 · 2020: 17 · 2019: 16 · 2018: 14 · 2017: 11 · 2016: 15 · 2015: 24 · 2014: 15 · 2013: 17 · 2012: 26
- FWCI
- 26.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG02331)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- growth hormone receptor, Laron syndrome, growth, aging, lifespan, insulin-like growth factor I, IGFBP-3, IGFBP-1, IGFBP-2, IGFBP-4, growth hormone signaling, dwarfism
- MeSH terms
- Aging, Animals, Carrier Proteins, Female, Heterozygote, Homozygote, Insulin-Like Growth Factor I, Longevity, Male, Mice, Inbred BALB C, Receptors, Somatotropin, Weight Gain, Gene Deletion, Insulin-Like Growth Factor Binding Protein 3, Mice
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