Introduction to the HESI‐Sponsored Inhibin Consortium

The existence of a compound from the tubular fraction of the testis which acts on the pituitary was first proposed in writing by McCullagh in 1932. This was inferred by observing the differential effects on the prostate and the pituitary when animals were administered water-soluble or ether-soluble extracts of testis. Because the water-soluble extract inhibited pituitary hypertrophy, he dubbed this moiety inhibin (his androitin for the ether-soluble actor later became testosterone). The early literature has been nicely reviewed (Ying, 1988). The early assays for inhibin were bioassays (e.g., Steinberger and Steinberger, 1976), later superseded by the more-sensitive radioimmunoassays, and now ELISAs. Inhibin has been used for several years as a clinical tool to help diagnose and categorize male infertility patients (e.g., Pierik et al., 1998; reviewed in Lockwood 2004, Adamopoulos and Koukkou, 2010, and Anderson and Sharpe, 2000). There has been a robust literature on various aspects on the physiology of the hormone, for example, trying to discern what controls circulating levels of Inhibin B in males (e.g., Ramaswamy et al., 1999), or describing the relationship between Inhibin and FSH (e.g., von Eckerdstein et al., 1999; Kamischke et al., 2001), or determining the impact of different germ cell populations on circulating Inhibin B levels (e.g., Pineau et al., 1989; Allenby et al., 1991; Clifton et al., 2002), or outlining Inhibin B’s role in development (Byrd et al., 1998) or evaluating its use as an epidemiologic marker (e.g., Ellingsen et al., 2007). There are numerous excellent reviews on this subject, a few of which are Meachem et al. (2001), de Kretser et al. (2004), and Stewart and Turner (2005). Because the large interand intraindividual variability makes sperm count and semen studies quite insensitive (e.g., Schrader et al., 1988), toxicologists and epidemiologists have long been looking for a more sensitive (i.e., less noisy and more responsive) biomarker of damage to the seminiferous tubules. Inhibin B seemed to fill this need, and indeed was found to respond to several different types of toxicities, especially over sufficient periods of time (Wallace et al., 1997; Tsatsoulis et al., 1988; Foppiani et al., 1999; Hild et al., 2001; Suescun et al., 2001; rev. in Stewart and Turner, 2005; Tunc et al., 2006).