This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chandrashekar, V. Articles by Kopchick, J. J. Search for Related Content PubMed PubMed Citation Articles by Chandrashekar, V. Articles by Kopchick, J. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB MENOTROPINS TESTOSTERONE Medline Plus Health Information Seniors' Health

Age-Related Alterations in Pituitary and Testicular Functions in Long-Lived Growth Hormone Receptor Gene-Disrupted Mice

Department of Physiology (V.C., C.R.D., E.R.M., A.B.), Southern Illinois University School of Medicine, Carbondale, Illinois 62901; Internal Medicine (J.S.R., A.B.), Southern Illinois University School of Medicine, Springfield, Illinois 62794; and Biomedical Sciences Department and Edison Biotechnology Institute (J.J.K.), College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701

Address all correspondence and requests for reprints to: Andrzej Bartke, Ph.D., Department of Internal Medicine, Geriatrics Research, Southern Illinois University School of Medicine, Springfield, Illinois 62794. E-mail: abartke{at}siumed.edu.

The somatotropic axis, GH, and IGF-I interact with the hypothalamic-pituitary-gonadal axis in health and disease. GH-resistant GH receptor-disrupted knockout (GHRKO) male mice are fertile but exhibit delayed puberty and decreases in plasma FSH levels, testicular content of LH, and prolactin (PRL) receptors, whereas PRL levels are elevated. Because the lifespan of GHRKO mice is much greater than the lifespan of their normal siblings, it was of interest to compare age-related changes in the hypothalamic-pituitary-gonadal axis in GHRKO and normal animals. Plasma IGF-I, insulin, PRL, LH, FSH, androstenedione and testosterone levels, and acute responses to GnRH and LH were measured in young (2–4 and 5–6 months of age) and old (18–19 and 23–26 months of age) male GHRKO mice and their normal siblings. Plasma IGF-I was not detectable in GHRKO mice. Plasma PRL levels increased with age in normal mice but declined in GHRKO males, and did not differ in old GHRKO and normal animals. Plasma LH responses to acute GnRH stimulation were attenuated in GHRKO mice but increased with age only in normal mice. Plasma FSH levels were decreased in GHRKO mice regardless of age. Plasma testosterone responses to LH stimulation were attenuated in old mice regardless of genotype, whereas plasma androstenedione responses were reduced with age only in GHRKO mice. Testicular IGF-I mRNA levels were normal in young and increased in old GHRKO mice, whereas testicular concentrations and total IGF-I levels were decreased in these animals. These findings indicate that GH resistance due to targeted disruption of the GH receptor gene in mice leads to suppression of testicular IGF-I levels, and modifies the effects of aging on plasma PRL levels and responses of the pituitary and testes to GnRH and LH stimulation. Plasma testosterone levels declined during aging in normal but not in GHRKO mice, and the age-related increase in the LH responses to exogenous GnRH was absent in GHRKO mice, perhaps reflecting a delay of aging in these remarkably long-lived animals.

This article has been cited by other articles:

				V. Chesnokova, S. Zonis, K. Kovacs, A. Ben-Shlomo, K. Wawrowsky, S. Bannykh, and S. Melmed p21Cip1 restrains pituitary tumor growth PNAS, November 11, 2008; 105(45): 17498 - 17503. [Abstract] [Full Text] [PDF]