title: Circulating bioactive follicle stimulating hormone and immunoreactive inhibin levels during the normal human menstrual cycle.
abstract: To examine the relationship between circulating levels of bioactive FSH (B-FSH) and immunoactive inhibin and oestradiol we studied five women during ovulatory cycles. Daily blood samples were collected from each subject during one menstrual cycle. B-FSH was measured using a modified, highly sensitive in-vitro rat granulosa cell bioassay. The inclusion of IGF-1 (10 micrograms/l) and transferrin (50 mg/l) in the assay system enhanced granulosa cell responsiveness to FSH and resulted in increased assay sensitivity. Inhibin was measured by a heterologous radioimmunoassay (RIA) using an antibody raised against 31 kDa bovine inhibin. Bioactive FSH (B-FSH) levels were closely correlated to those of immunoactive FSH (I-FSH, r = 0.79, P less than 0.001) throughout the cycle. Peak levels of B-FSH were observed during the early follicular phase (day -13, 44.7 +/- 9.6 IU/l, mean +/- SEM) and during the midcycle surge (35.2 +/- 6.2 IU/l); lowest levels occurring during the luteal phase (nadir 3.9 +/- 0.27 IU/l). Plasma oestradiol levels increased significantly during the follicular phase (P less than 0.001) to a peak on day -1 and were negatively correlated with B-FSH during the late follicular phase (day -8 to -1; r = -0.45, P less than 0.02). There was no change in the concentration of inhibin (range 55.3-72.3 U/l) during the follicular phase until day -2 after which an increase to a midcycle peak of 139 +/- 10.6 U/l was observed. No correlation was observed between inhibin and B-FSH during the follicular phase. A second increase in the concentration of inhibin was seen during the luteal phase; peak levels occurred by day 6 (311 +/- 25.8 U/l), remained elevated until day 12, and were negatively correlated with B-FSH (r = -0.53, P less than 0.001). No correlation was observed between oestradiol and inhibin or B-FSH during the luteal phase. We conclude that (1) oestradiol secretion from the growing follicle is primarily responsible for the negative feedback regulation of B-FSH resulting in a change from peak levels in the early follicular phase to basal levels in the late follicular phase; (2) significant and sustained increase in peripheral inhibin concentrations occur mostly during the luteal phase; and (3) regulation of FSH secretion by inhibin occurs primarily in the luteal phase. These results suggest a temporal relationship between oestradiol and inhibin in the negative feedback regulation of FSH in vivo.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Edinburgh, UK.
authors.forename: K
authors.initials: K
authors.lastname: Reddi
authors.forename: E J
authors.initials: EJ
authors.lastname: Wickings
authors.forename: A S
authors.initials: AS
authors.lastname: McNeilly
authors.forename: D T
authors.initials: DT
authors.lastname: Baird
authors.forename: S G
authors.initials: SG
authors.lastname: Hillier
mesh_terms: D000328:Adult; D001681:Biological Assay / Q000379:methods; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood*; D005498:Follicular Phase / Q000502:physiology; D006801:Humans; D007265:Inhibins / Q000097:blood*; D008183:Luteal Phase / Q000502:physiology; D007986:Luteinizing Hormone / Q000097:blood; D008598:Menstruation / Q000097:blood*; D011374:Progesterone / Q000097:blood; D011863:Radioimmunoassay / Q000379:methods
chemical_list: D011374:Progesterone; D004958:Estradiol; D007265:Inhibins; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone