Acquisition of regulatory mechanisms for gonadotropin receptors and steroidogenesis in the maturing rat testis.

Abstract

Testicular LH, lactogen, and estrogen receptors and in vitro steroidogenic and cAMP responses were measured in rats between the ages of 1 and 60 days. Testicular LH and lactogen receptors increased gradually with advancing age, although there was no direct correlation between the concentrations of the two receptors. Cytosolic estrogen receptors were present in the testis at 6 days of age, but α-fetoprotein represented the major estrogen-binding component until 20 days of age. The basal and maximally stimulated in vitro production rates of testosterone, pregnenolone, and cAMP per unit weight were more than 10-fold higher in neonatal rats than in 60-dayold animals. These production rates decreased rapidly to a nadir at 15 days and increased again between 15 and 60 days of age. Treatment of 1-day-old rats with a low dose of hCG (10 IU/kg daily) for 3 days caused an increase of 91% (P < 0.01) -in LH receptors per testis. This effect of hCG diminished gradually with advancing age and became insignificant in animals older than 23 days. A single high dose of hCG (600 IU/kg) caused rapid loss of free testicular LH receptors within 12–24 h in animals of all ages. The recovery of LH-binding sites occurred within 2–3 days in 5-day-old animals, but became progressively slower with advancing age and reached 14 days in 60-day-old rats. The in vitro testosterone responses of testes from 5-dayold rats were increased by 2- to 3-fold when measured 3 days after the high dose of hCG. This positive effect of hCG treatment also decreased with age and became insignificant in animals older than 20 days. In adult animals, the same hCG treatment caused complete loss of testosterone responses to gonadotropic stimulation, consistent with the development of steroidogenic lesions in the Leydig cell. These results demonstrate that the production of testosterone, pregnenolone, and cAMP per unit tissue weight is higher in the neonatal testis. Also, hCG has a rapid stimulatory effect upon LH receptors and steroidogenesis in the neonatal testis, but does not cause LH receptor downregulation and steroidogenic lesions at this age. These stimulatory responses to hCG gradually diminish during development and are replaced by the adult-type responses, with sterodogenic lesions and LH receptor down-regulation. The transition from neonatal to adult-type responses which occurs around 15 days of age emphasizes the functional differences between fetal and adult populations of Leydig cells. The development of estrogenmediated inhibitory actions in the testis may contribute to the differences observed between neonatal and adult rat Leydig cells.