SERUM CONCENTRATIONS OF DIMERIC INHIBIN DURING THE SPONTANEOUS HUMAN MENSTRUAL-CYCLE AND AFTER TREATMENT WITH EXOGENOUS GONADOTROPIN

A recently described two-site enzyme immunoassay incorporating a pre-assay oxidation step was validated and used to measure serum concentrations of dimeric inhibin in five normally cycling women and in 13 women undergoing gonadotrophin therapy. Recombinant human inhibin A (standard) gave an assay response curve which was parallel to those for human serum samples and recovery of exogenous inhibin added to serum samples before assay was quantitative (109 +/- 8%, n = 11). During the normal menstrual cycle dimeric inhibin concentration increased from 9.0 +/- 2.0 pg/ml during the early follicular phase to reach a mid-cycle peak of 55.3 +/- 11.1 pg/ml coincident with the pre-ovulatory gonadotrophin surge. After falling to 27.9 +/- 5.7 pg/ml 1 day after the luteinizing hormone surge, inhibin then rose in parallel with serum progesterone to reach a peak value of 115.6 +/- 19.3 pg/ml during the mid-luteal phase, before falling to 14.1 +/- 4.9 pg/ml by the onset of next menses. During the follicular phase, dimeric inhibin concentrations were closely correlated with those of serum oestradiol (r = 0.69; P < 0.001), whereas during the luteal phase they were most closely correlated with serum progesterone concentrations (r = 0.73; P < 0.001). Daily treatment with human menopausal gonadotrophin promoted a progressive increase in serum dimeric inhibin concentration which increased similar to 20-fold in 6 days. In the same period total ac-inhibin (measured by radioimmunoassay) increased -5-fold, while serum oestradiol increased similar to 30-fold. Although the assay cross-reacted with dimeric inhibin forms of molecular masses in the range 200-30 kDa, chromatography of superovulatory human serum revealed that the fully processed similar to 30 kDa form is the predominant circulating form, although a proportion of this (similar to 30%) is reversibly associated with serum binding protein(s).