GnRH-Receptor Interaction. VI. Effect of Progesterone and Estradiol on Hypophyseal Receptors for GnRH, and Serum and Hypophyseal Concentrations of Gonadotropins in Ovariectomized Ewes1

The effects of estradiol and progesterone on 1) hypophyseal and serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH); 2) hypothalamic content of gonadotropin releasing hormone (GnRH); and 3) numbers of receptors for GnRH were examined in ovariectomized ewes. Three days after ovariectomy, ewes were given 16 mg progesterone (n = 5), 0.7 mg estradiol (n = 5) or 16 mg progesterone plus 0.7 mg estradiol (n = 5) s.c. in ethanol twice daily for 3 weeks prior to slaughter. Ten control ewes were given injections of ethanol according to the same schedule. Five intact ewes were killed 12 days after an induced ovulation. Blood samples were collected daily for 4 days prior to slaughter, and the serum was analyzed for concentrations of progesterone, estradiol, LH, and FSH. Hypothalami were removed after sacrifice and the amount of GnRH present in the preoptic area, median eminence, and hypothalamus proper was determined. In addition, the pituitary gland from each animal was removed and the number of receptors for GnRH and concentrations of LH, FSH, and prolactin were measured. Steroid treatment produced concentrations of estradiol and progesterone similar to those observed during late pregnancy in ewes. Administration of either progesterone or estradiol, suppressed (P<0.01) serum concentrations of LH to levels similar to those observed in intact ewes. In contrast, serum concentrations of FSH were suppressed (P<0.01) only in the ewes receiving injections of estradiol (alone or in combination with progesterone). Although progesterone suppressed serum concentrations of LH, it had no effect on hypophyseal concentrations of LH or on serum or hypophyseal concentrations of FSH; administration of estradiol suppressed hypophyseal concentrations of LU (P<0.05) and FSH (P<0.01) and this effect was not antagonized by progesterone. In contrast to serum and pituitary concentrations of gonadotropins, the number of receptors for GnRH was higher (P<0.01) in ovariectomized ewes receiving injections of estradiol (or estradiol plus progesterone) than in the other groups. Contents of GnRH in the three hypothalamic areas examined did not change (P>0.05) as a result of treatment. Likewise, neither hypophyseal weight nor prolactin content was affected by steroid treatment, suggesting that the effects of the steroids were limited to the gonadotrophs. These data indicate that estradiol can increase the number of receptors for GnRH, while the quantity of LH and FSH released into the circulation or contained in the pituitary decreases. Thus, the effects of estradiol appear to be mediated at the level of the pituitary gland. In contrast, the inhibitory effect of progesterone on secretion of LH is not mediated via receptors for GnRH or pituitary concentrations of LH, suggesting an influence at higher neural centers.