The physiological significance of pulsatile LHRH secretion in man: gonadotrophin responses to physiological doses of pulsatile versus continuous LHRH administration

This study tested whether pulsatile LHRH stimulation of the pituitary is required for normal gonadotrophin secretion in man. Four men with idiopathic hypogonadotrophic hypogonadism (IHH) and presumed endogenous LHRH deficiency were taken off all hormonal replacement for 5-6 weeks, then 5 micrograms LHRH was administered every 2 h for 1 week in order to prime pituitary gonadotrophin responsiveness. A physiological dose of LHRH (10 micrograms every 2 h) was then administered in both pulsatile and continuous regimens, in varying order, to each man. Pulsatile LHRH was capable of stimulating LH (as measured by bioassay) and FSH secretion, while continuous administration of LHRH was not. Serum LH, measured by RIA and bioassay, and FSH and free alpha-subunit levels, measured by RIA, increased significantly (P less than 0.05) over pretreatment levels during pulsatile LHRH administration. In contrast, bioactive LH and immunoactive FSH did not change significantly compared to pretreatment values during continuous infusion of the same total LHRH dose, although immunoactive LH and free alpha-subunit levels did increase significantly (P less than 0.05). The ratio of LH bioactivity to immunoactivity was significantly lower during the continuous compared to pulsatile LHRH regimen (P less than 0.001). Similar serum LHRH levels were achieved during pulsatile and continuous infusions. Serum testosterone and oestradiol levels did not increase significantly from pretreatment levels during either regimen of LHRH administration. It is concluded that a pulsatile LHRH signal pattern is essential for normal pituitary gonadotrophin secretion in men with IHH. Continuous infusion of a physiological dose of LHRH, which produced serum LHRH levels which were indistinguishable from those found during pulsatile administration, failed to stimulate FSH or bioactive LH secretion.