The effect of sex steroids on pituitary responsiveness to gonadotropin releasing hormone

Gonadotropin secretion is controlled mainly by feedback effects of gonadal steroids at hypothalamic sites. The existence of a regulatory role of gonadal steroids at the pituitary has also been suggested. Results obtained with exogenous steroids as reflected by pituitary responsiveness to GnRH are, however, contradictory. Discrepancies can be attributed to types of steroids administered, doses used and the impossibility to distinguish between the effect on the pituitary from that on the hypothalamus. To overcome the above limitations, the effect of endogenous steroids on pituitary response to a standard dose of GnRH (Ayerst) was investigated in primary amenorrheic patients with isolated hypothalamic failure. The effect of GnRH was investigated under various steroidal environments obtained during cycles induced by exogenous gonadotropins. In the first phase (in the absence of ovarian steroids) GnRH evoked an increase in both LH and FSH. In the second phase, when the endogenous level of estradiol was high. GnRH did not induce an FSH release. Elevation of LH secretion began at the same time as in the first phase but was prolonged and reached higher values-coinciding with the first observed increase in plasma progesterone. In the third phase, the luteal phase (high estrogen and progesterone levels), GnRH failed to elicit either LH or FSH release. It seems therefore that estrogens sensitize the pituitary to respond to GnRH with a selective augmented LH secretion. Steroidal environment of the luteal phase diminishes the pituitary responsiveness to GnRH with respect to both FSH and LH release. It can thus be postulated that steroids can modulate pituitary responsiveness to hypothalamic stimuli.