Pituitary Gonadotropin-Releasing Hormone Receptor Regulation in Mice. II: Females*

Abstract

The regulation of pituitary GnRH receptors (GnRH-R) by gonadal steroids was examined in female mice housed in a constant environment (six to 8 per cage in same room as males). A 60% decrease in GnRH-R occurred 7 days after ovariectomy (OVX) (9.2 +/- 0.9 fmol/pituitary OVX vs. 25 +/- 2 for intact random estrous cycle controls). The receptor affinity (Ka 1.86 X 10(9) M-1) remained constant in intact and OVX female mouse pituitary particles. The pattern of GnRH-R fall after OVX was similar to that found in male mice, except that the GnRH-R decrease began some 6 h later than in males and serum LH also rose more slowly. Serum FSH was significantly elevated 6 h post OVX. In contrast to males, pituitary LH, in spite of a rapid fall (60%) at 12 h, regained the random, estrous cycle control value by 4 days post OVX and then increased to above this level. Pituitary FSH, unlike in males, remained at the intact value (3.1 +/- 0.24 micrograms/pituitary) up to 24 h post OVX and then gradually rose to 7.9 +/- 0.37 micrograms/pituitary on day 4 and 15.5 +/- 0.32 micrograms/pituitary on day 7. Treatment of OVX female mice with estradiol-17 beta (300 ng/day) attenuated the postcastration GnRH-R fall, and was more effective when combined with progesterone (375 micrograms/day). Progesterone alone was ineffective. The GnRH-R fall post OVX persisted for up to 2 months, despite elevated serum and pituitary LH and FSH levels. GnRH-R fell by 40% in lactating mice (20.6 +/- 0.95-lactating vs. 32.4 +/- 1.25 fmol/pituitary-random, estrous cycling females). Serum LH was reduced by 70% in lactating mice. These findings are qualitatively and quantitatively similar to those in lactating rats suggesting that, in this physiological situation, a similar mechanism may account for the receptor fall in both species. In sex reversed (Sxr) mice (genotypic female-phenotypic male) GnRH-R values were about 50% higher than those of intact normal male and normal, random estrous cycling, female values. This was the only situation in mice in which pituitary GnRH-R increases were observed to date. Serum and pituitary LH and FSH values in Sxr mice were elevated, especially when compared with normal, random estrous cycling female controls. The results indicate that pituitary GnRH-R of female mice fall in response to removal of gonadal steroid feedback, in the same way as males.(ABSTRACT TRUNCATED AT 400 WORDS)