Aging Changes in Testicular Responsivity to Gonadotropin Stimulation in Rats

Abstract

This study examined the effects of aging on testicular endocrine function and response to gonadotropin stimulation in male rats. Sprague-Dawley rats of 4 and 18 months were used throughout. Peripheral blood, testicular venous blood and endogenous testicular production were quantified for testosterone (T), 20 ? dihydroxyprogesterone (20?OH P), progesterone (P) and estradiol-17 ? (E_2). The levels of both P and E_2 were similar in both age groups but significantly less T and 20?OH P were found in testicular venous plasma and testis of aged rats. However, serum pH as quantified by RIA showed no age-related difference. In vitro incubations of both decapsulated testicular tissue and isolated Leydig cells with hCG (0-100 mIU) showed significantly less T production by the aged rats at basal levels and at all doses of hCG. Two groups of 4 and 18 month rats were injected i.v. with 50 IU hCG to study the in vivo response to gonadotropin stimulation. Peripheral blood was drawn at 0, 1 and 3 hours after hCG injection. Testicular venous (TV) blood and endogenous testicular production (EP) were determined 5 hours after hCG. T, P, E_2 and 20?OH P were quantified in all samples. Results indicate no age-related difference in P or E_2 production before or after hCG. T and 20?OH P levels were significantly lower in TV blood and EP 3 Hr after injection. Peripheral blood concentrations of T showed significantly higher levels in 4M rats at 0 and 1 hours, however, at 3 hours post-hCG, peripheral serum T levels were found to be similar in both age groups. This similarity in peripheral T levels did not reflect secretory differences as demonstrated by TV and EP of T 3 hours after hCG, but was more likely due to differences in the metabolic clearance rates (MCR) of T. We therefore conclude that reproductive aging in rats is in part due to an inherent defect in testicular function. This defect may be a lesion in the steroidogenic enzymes leading to the formation of T which lies distal to LH binding, cAMP production and P formation. Testicular E_2 may not play a major role in reproductive senescence in rats.