Feedback effects of estradiol and progesterone upon gonadotropin and prolactin release

The relationship between estradiol- and progesterone-mediated gonadotropin release and steroid-induced changes in prolactin levels was investigated in an improved human experimental model. Three women who had undergone bilateral ovariectomy were studied after they had received a subcutaneous implant of one 25-mg estradiol (E2) pellet. Serum E2 levels remained between 60 and 125 pg/ml, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were within the normal or slightly elevated range. Serum prolactin (PRL) levels were normal. Each woman received intramuscular injections of gradually increasing doses of estradiol benzoate (E2B) alone and in combination with progesterone (P) in 7 different experiments. An E2B-induced rise in E2 levels comparable to that observed at midcycle elicited a clearly defined LH surge but no change in FSH and PRL. Rising E2 concentrations followed by increasing P levels caused LH and FSH release but no change in PRL. When only P was administered or when serum P levels rose concomitantly with E2 levels, PRL and gonadotropin levels remained unchanged. These data indicate that a surge of E2 similar to that observed at midcycle triggers an acute release of LH only. Moreover, P levels commensurate with those found at mid-cycle facilitate an E2-mediated LH release and induce a concomitant peak in FSH. The lack of a significant increase in PRL levels suggests that different mechanisms are responsible for the pituitary release of PRL and gonadotropins.