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(728) THE EFFECT OF AGING ON TESTICULAR ENDOCRINE FUNCTION IN GROWTH HORMONE RECEPTOR GENE DISRUPTED MICE. Chandrashekar, Varadaraj1, Bartke, Andrzej2, Kopchick, John3, 1 Department of Physiology, Carbondale, IL2 Internal Medicine, Springfield, IL3 Biomedical Sciences Department and Edison Biotechnology Institute, Athens, OH ABSTRACT- It is known that insulin-like growth factor-I (IGF-I) has a profound influence on the neuroendocrine-gonadal function. GH receptor gene knockout (GHR-KO) mice are IGF-I-deficient (Endocrinology 142:3443-3450, 2001). Recently it has been shown that GHR-KO mice live significantly longer than their normal siblings, possibly due to the suppression of the somatotropic axis, resulting in a reduction in the IGF-I-insulin signaling pathway. However, it is not known whether these changes also affect the androgen secretion in aging GHR-KO mice. To evaluate this, young (3-4 months of age) and aging (18-19 months of age) male GHR-KO mice and their normal male siblings were divided into two groups and injected (ip) with either saline or oLH (NIH-26; 0.3 KEY WORDS: LH, Aging, IGF-I, Leydig cells |
g/g BW) in saline (N= 5-10 mice/treatment). One hour later, blood was obtained via heart puncture. Plasma testosterone levels were measured by RIA. The basal testosterone concentrations were decreased (P<0.005) in aging normal siblings, whereas there was no change in aging GHR-KO mice compared with the respective young animals. As expected, LH treatment significantly (P<0.001) increased plasma testosterone levels in both young and aging, normal and GHR-KO mice. Relative to young normal siblings, this testosterone response was attenuated in aging normal (P<0.01), young (P<0.001) and aging GHR-KO (P<0.001) mice. Furthermore, the already decreased plasma testosterone response to LH treatment in young GHR gene disrupted mice was further reduced (P<0.001) in aging GHR-KO mice. These results indicate that the testes of IGF-I-deficient-GHR-KO mice are not fully responsive to LH action and the aging process further deteriorates the Leydig cell function. Thus, IGF-I plays an important role in bringing the full effect of LH on testicular endocrine function. However, it is not clear whether the alteration in testosterone secretion observed in GHR-KO mice contributes to the extension of the life span in these animals (Supported by NIH Grants HD-37950 and HD-37672).