Age-Related Alterations of Isolated Rat Leydig Cell Function: Gonadotropin Receptors, Adenosine 3', 5'-Monophosphate Response, and Testosterone Secretion

Decreased serum testosterone has been reported in old male rats, but in vivo studies have shown decreased gonadotropin levels and normal testis response to 120 min or more of gonadotropin stimulation, leaving doubt as to whether an aging defect exists in the Leydig cell per se. We compared the function of Leydig cells from old Wistar rats (22-25 months) with cells from mature rats (6-9 months) in vitro. The cells from old rats showed a 77% diminution in testosterone secretory response to hCG after incubation with various concentrations of hCG for 120 min. Cells from old animals reached a maximum response at a hCG concentration of 0.2 ng⁄ml, and cells from mature rats reached a maximum response at a hCG concentration of 0.5 ng⁄ml. Testosterone secretory response to 0.2 and 0.5 ng/ml hCG was also diminished in the old animals after incubations ranging from 60-180 min Leydig cells from old rats had 27% fewer gonadotropin receptors than mature rats (P < 0.001); however, total intracellular cAMP and protein-bound cAMP increases after hCG were not significantly different. Our findings point to the development of an intrinsic Leydig cell defect with age in the strain of rats studied, not reversible by hCG stimulation up to 3 h in vitro. They also suggest that the alteration responsible for the testosterone secretory hyporesponsiveness of Leydig cells from old rats is probably not attributable to a reduction in gonadotropin receptors or deficient cAMP production.