Age Related Changes in the Production and Metabolism of Testicular Steroids in the Rat

Abstract

Age-related changes in the production and metabolism of testicular steroids were studied by chronic in vivo hCG stimulation of 4 month (Y) and 18 month ( 0) rats, followed by in vitro hCG stimulation of the chronically stimulated testis tissue. The 0 showed a reduced initial response to hCG with significantly lower levels of T on D1 and D2. Although on D4-D10 the peripheral levels of T were not significantly different in Y and 0, at D1O the Y had returned to basal levels and the 0 were still at 3x basal. The D1O endogenous levels of T were also significantly higher in the 0. In vitro stimulation of the chronically stimulated testis tissue showed both Y and 0 unresponsive to further stimulation, but the 0 produced more T both with and without hCG stimulation. These facts may indicate some failure in the desensitization process in the 0. Another difference between Y and 0 was significantly higher levels of endogenous 20 ? hydroxyprogesterone in the o, suggesting possible differences in local control mechanisms. Neither chronic in vivo hCG stimulation nor in vitro aromatization of testosterone (T) to estradiol ( E2) resulted in any significant differences between Y and 0 in production or utilization of estradiol. However, during chronic hCG stimulation there were age-related differences in the ratios of T/E2 suggesting the possibility of an extra-testicular role for E2 in age-related changes. Aromatization of T resulted in lower levels of E1 and of ?4D in the 0 as compared to the Y. Also, when stimulated with hCG the Y, but not the 0, exhibited a significant decrease in production of ?4D. Other metabolites of T such as 7? hydroxytestosterone (7 ? OHT) and 7 ? hydroxyandrostendione (7 ? OH ? 4D) did not show age-related differences. Comparision of the clearance of T in acutely castrated 0 and Y rats showed that the 0 clear T more slowly than the Y. When injected with supraphysiological doses of T, both Y and 0 castratedrats cleared T faster than after acute castration. The 0 still showed slower t 1/2? and t 1/2? after these injections but the amount of T cleared from the blood calculated as MCR ( liters of blood cleared/ kg of body wt/ day) was not significantly different in the Y and 0.