Regulation of pituitary gonadotropin-releasing hormone receptors by gonadal hormones.

Abstract

The regulatory role of pituitary gonadotropinreleasing hormone (GnRH) receptors in the control of gonadotropin secretion was investigated in male and female rats after castration and sex steroid hormone replacement. GnRH receptors were measured in homogenates of individual pituitaries by equilibration with 125I-labeled [D-Ser(tBu)6]des-Gly10-GnRH Nethylamide, and compared with serum and pituitary LH concentrations. The equilibrium association constants (Ka) were 6.1 and 5.1 × 109 M-1 for intact and castrate male rat pituitaries, respectively. After orchidectomy, pituitary GnRH receptor concentration increased by 75% at 24 h, from 150 fmol to 250 fmol/gland, while serum LH levels increased 10-fold (30 to 300 ng/ml). There was a further slight increase in the GnRH receptor concentration (to 370 fmol/gland) and serum LH (to 500 ng/ml) over the ensuing 10 days, and at 15 and 20 days GnRH receptors were 304 and 306 fmol/gland, respectively. There was a highly significant (P < 0.001) positive correlation between basal serum LH and FSH concentrations and the pituitary GnRH receptor content measured in individual animals. Treatment with testosterone propionate (100 fig/day) completely prevented the GnRH receptor and serum LH responses to castration, while 50 μg testosterone propionate/day produced variable results. 17/8-Estradiol (5 μg/day), diethylstilbestrol (5 μg/day), and dihydrotestosterone (50 μg/day) prevented the increase in GnRH receptors 5 days after orchidectomy, while serum LH levels were only partially suppressed. In adult female rats, ovariectomy caused a 2- to 4-fold increase in serum LH in the first 3 days, followed by a larger secondary increase of 10- to 15-fold after 5 days. GnRH receptor concentration increased from 130 to 240 fmol/gland on the third day after operation, just before the major rise in serum LH. 17β-Estradiol (1 μg/day), progesterone (2.5 mg/day), and estradiol plus progesterone inhibited the postovariectomy rise in GnRH receptors for up to 11 days. Estradiol or progesterone given alone prevented the initial rise in serum LH but not the secondary rise from 5 days on, while the combination of estradiol plus progesterone was effective in this regard for the entire treatment period. These results indicate that increased pituitary binding of GnRH is a significant component of the mechanism responsible for postcastration elevations of gonadotropin secretion.