An antagonist analog of GnRH, (Ac-delta 3-Pro1,p-F-D-Phe2,D-Trp3,6)GnRH (4F-antagonist), was administered to normal women and women with hypergonadotropic hypogonadism. Serum FSH levels were determined by both the granulosa cell aromatase bioassay and RIA. The constant infusion of 4F-antagonist (30 micrograms/kg.h) to the four hypogonadal women resulted in a more pronounced decline in bioactive FSH (62%) than in immunoreactive FSH levels (30%), and the FSH bioactive to immunoreactive ratio decreased significantly (P less than 0.05). Infusion of 4F-antagonist in normal women in the midfollicular phase revealed a similar pattern of suppression of bioactive (64%) and immunoreactive FSH (29%). When 4F-antagonist was administered sc at a dose of 80 micrograms/kg twice daily for 3 days to normal women in the midfollicular phase of their cycles, the bioactive FSH response was biphasic, with the maximal decrease on the second day, followed by return to basal levels on the third day. Correspondingly, there was a precipitous decline in serum estradiol (apparent demise of the dominant follicle), followed by a progressive rise in estradiol levels. Thus, in contrast to immunoreactive FSH levels, bioactive FSH more clearly reflects the biological action of FSH on the follicle in response to GnRH antagonist administration in women. The disparity in the quantitative decline between serum bioactive and immunoreactive FSH levels after presumed blockade of the GnRH receptor may reflect the microheterogeneity of the FSH molecule and suggests that alterations in the biological activity of secreted FSH may be GnRH dependent.
Adult Biological Assay