Assessments of the functional capacity of the gonadotrophs in men: effects of estrogen and clomiphene

Abstract

Serum LH and FSH responses to serial injections of LRF with small (10 mug x 5), large (150 mug x 5), decremental (300 to 10 mug), and incremental (10 to 300 mug) doses at 2-hour intervals were assessed in eugonadal men. At constant doses, pulses of LRF induced pulsatile LH release which was qualitatively similar but quantitatively greater for the large than for the small dose of LRF. There were no periods of refractoriness or augmentation of subsequent responses from prior exposure to LRF when administered at 2-hour intervals. LH responses to incremental and decremental doses of LRF resulted in corresponding measurable changes in the magnitude of pituitary LH release. The FSH responses to pulses of LRF at all doses tested were uniformly small. These data suggest that analyses of the initial and integrated release (10 h experiment) to pulses of LRF may disclose the functional capacity of the gonadotrophs and that small variations in the endogenous LRF delivered may represent a significant factor in the control of LH release. The small dose (10 mug x 5) of pulses of LRF was utilized in the assessment of estrogen and clomiphene treatments on the functional capacity of the gonadotrophs in normal men. Compared with the pretreatment results, both constant doses of ethinyl estradiol (50 mug/day x 7 days) and incremental doses of estradiol benzoate (100 to 400 mug, twice daily injections x 4 d) induced an attenuation of the initial release as well as of the integrated response 10 h) to pulses of LRF. Clomiphene treatment (100 mg/day x 5 d), likewise, resulted in a reduction of gonadotropin release to all pulses of LRF. These data suggest that circulating estrogen in intact men may have both a negative and a positive feedback effect on the gonadotrophs and that the testicular estrogen secretion as well as the extraglandular sources of estrogen, may play a critical role in the regulations of gonadotropin secretion in man.