Characterization of plasma inhibin forms in fertile and infertile men

BACKGROUND: The reciprocal relationship between plasma FSH and inhibin B generally reflects the state of spermatogenesis but data in some settings indicate further complexity in their relationship. Inhibin circulates as a range of higher molecular weight (mol wt) forms of varying bioactivity such that the serum profile of inhibin forms may differ between normal men and those with varying types of spermatogenic failure. The aim of this study was to establish if the inhibin B mol wt distribution was altered in men with infertility. METHODS: The mol wt profiles of inhibin B and free alpha-subunit were determined in plasma of fertile (n = 11) and infertile (n = 17) men using a combined immunoaffinity chromatography, preparative SDS-PAGE and electro-elution procedure and fractions assayed using ELISAs for inhibin B, total inhibin (all forms containing the alpha-subunit) and free alpha-subunit. RESULTS: Inhibin B was identified as precursor (60-65 k) and mature (26-30 k) forms in plasma in similar proportions (29%) in fertile men and oligospermic men (25%), but was undetectable in azoospermic men. The free alpha-subunit detected by the pro-alphaC ELISA was identified as both the precursor and processed (pro-alphaC) forms with similar proportions in fertile (8%) and all infertile (4-14%) men. The pro-alphaC ELISA did not detect the precursor forms of inhibin B in plasma while the inhibin B ELISA detected all total inhibin forms following removal of pro-containing forms by immunoabsorption. CONCLUSIONS: (i) the proportions of precursor inhibin B and alpha-subunit forms in the circulation are unchanged in men with spermatogenic disorders indicating there is no alteration of the Sertoli cell inhibin secretory pattern; (ii) these fractionation studies indicate that pro-alphaC and inhibin B ELISAs specifically detect the free alpha-subunit and inhibin B forms present in male plasma.