Inhibin B as a potential biomarker of testicular toxicity.
Inhibin B is a glycoprotein produced predominantly by Sertoli cells which regulates pituitary FSH release by a negative feedback loop. The regulation of inhibin B is complex with changes in the pattern of secretion occurring during development, and many factors such as FSH, testosterone, Sertoli cell proliferation and germ cell complement likely to contribute to overall production. Systemic inhibin B concentrations seem to reflect the extreme ends of spermatogenic status with high levels of inhibin B observed in normal, fertile individuals and lower levels of inhibin B in individuals with severe damage to the testis as a result of germ cell depletion. Inhibin B has proved valuable in epidemiological studies exploring male infertility with data showing that inhibin B combined with FSH measurements has a higher positive predictive value for detecting male infertility than either alone. Inhibin B is proposed as a potential biomarker of testicular toxicity in rodent toxicity studies to compliment traditional endpoints. In pharmaceutical development, inhibin B might allow better linkage between animal study results and subsequent monitoring of testicular function in clinical trials. An international, intercompany project has been initiated to evaluate the overall suitability and limitations of inhibin B as a biomarker of testicular toxicity.
Stewart
Jane
J
Reproductive Toxicology, AstraZeneca Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK.
Turner
Katie J
KJ
D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis; D006801:Humans; D007265:Inhibins / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D012377:Rodentia; D013091:Spermatogenesis / Q000502:physiology; D013733:Testicular Diseases / Q000139:chemically induced*; D013737:Testis / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
D015415:Biomarkers; C422364:inhibin B; D007265:Inhibins