Alteration of follicle regulatory protein levels in human reproductive disorders

Recently, a follicle regulatory protein was identified that suppresses ovarian response to gonadotropins. In this study, the serum levels of follicle regulatory protein were measured in five groups of women: 1) reproductive age undergoing oophorectomy (N = 101, 2) postmenopausal (N = 10), 3) ovulatory (N = 131, 4) anovulatory (N = 161, and 5) anovulatory receiving clomiphene citrate therapy (N = 14). Follicle regulatory protein-related immunoreactivity was measured by a competitive enzyme-linked immunosorbent assay, while peripheral estradiol and progesterone levels were determined by established radioimmunoassay. Concentration of follicle regulatory protein in serum in all ovariectomized patients decreased significantly from preoperative levels. The postmenopausal women had significantly lower follicle regulatory protein levels than did ovulatory and anovulatory women. Patients with low levels of serum estradiol in the early follicular phase exhibited either significantly elevated or suppressed follicle regulatory protein levels compared with patients with normal estradiol concentrations, suggesting two different etiologies for ovarian dysfunction. Eleven to 12 and 22–23 days after the onset of the last menstrual period, patients with elevated follicle regulatory protein levels were found to be anovulatory. These observations suggest that elevated intraovarian levels of follicle regulatory protein may cause a disruption of follicular maturation that leads to anovulation and, in some cases, to resistance to clomiphene citrate therapy.