Androgens and estrogens in their negative feedback action in the hypothalamo-pituitary-testis axis: site of action and evidence of their interaction.

This paper reviews our research efforts with regard to the negative feedback effects of androgens and estrogens on the secretion of luteinizing hormone (LH) by the hypothalamo-pituitary unit. Three approaches were used: (1) administration of single sex steroids to eugonadal men, (2) administration of single sex steroids to agonadal men and (3) administration of antiandrogens and antiestrogens to eugonadal men. It was found that estrogen administration to agonadal men suppressed basal and LH-RH-stimulated LH levels and LH pulse amplitude while LH pulse frequency remained unaffected. Dihydrotestosterone did not suppress basal and LH-RH-stimulated LH levels in either eugonadal and agonadal men. Antiandrogens and antiestrogens evoked almost identical effects: an increase in LH pulse frequency and amplitude and in basal and LH-RH-stimulated LH levels. On comparison of results of studies with single sex steroid administration and of studies with the antihormones there were unexpected and even conflicting findings. These can be resolved by assuming an interaction of the receptor mechanisms of androgens and estrogens in their feedback action. Blocking of androgen receptors impairs the action of estradiol in this system and vice versa. A similar interaction between estradiol and progesterone exists in women. Androgens appear to regulate LH pulse frequency, the latter is determined at the level of the hypothalamus. Estrogens appear to regulate predominantly parameters of LH secretion as LH pulse amplitude and basal and LH-RH-stimulated LH levels. These effects must be viewed in terms of preponderance and not of mutual exclusion.