Similarities and differences in progesterone and androgens in modulation of LH, FSH and PRL release: Unexpected properties of flutamide

The purpose of this study was to determine if the similarity of effect of progesterone and androgens on antagonism of estrogen-induced prolactin release also applied to the regulation of LH and FSH release. An additional objective was to examine the effect of the antiandrogen, flutamide, upon the ability of progesterone to induce gonadotropin secretion. Using the ovariectomized estrogen-primed immature rat, testosterone propionate suppressed LH and FSH secretion, whereas dihydrotestosterone only suppressed serum LH levels. In contrast, progesterone significantly elevated both serum LH and FSH levels. Thus, with respect to regulation of gonadotropin secretion, the effects of androgens and progesterone were dissimilar. In the estrogen-primed ovariectomized immature rat, flutamide was found to suppress LH, FSH and PRL secretion. Progesterone (0.8 mg/kg body wt) was incapable of overcoming this suppressive effect of flutamide. The effect of flutamide on gonadotropin secretion required estrogen priming. The effect of flutamide in suppressing LH, FSH and PRL release was not through suppression of an adrenal steroid as shown by adrenalectomy or the use of RU486. In the PMSG primed immature rat, flutamide had no effect on basal gonadotropin levels or ovulation. However, flutamide antagonized progesterone and triamcinolone acetonide-induced gonadotropin surges and blocked their ability to facilitate ovulation. These studies demonstrate that in the ovariectomized estrogen-primed immature rat flutamide has potent neuroendocrine regulatory ability leading to suppression of LH, FSH and PRL release. Flutamide also blocked progesterone and triamcinolone acetonide induced gonadotropin surges and ovulation in PMSG-primed immature female rats.