inhibin

Inhibin is a dimeric glycoprotein hormone belonging to the TGF-β superfamily, existing as inhibin A and inhibin B, each composed of a common alpha subunit linked to a beta subunit (beta-A or beta-B). In males, Sertoli cells secrete inhibin B in response to FSH stimulation during spermatogenesis; inhibin B then exerts negative feedback specifically on FSH (not LH) at the anterior pituitary, without significantly affecting hypothalamic GnRH. This selective feedback loop helps distinguish inhibin's role from testosterone, which feeds back on both LH and GnRH.

In females, granulosa cells of the ovarian follicles produce inhibin B during the follicular phase and inhibin A during the luteal phase, both suppressing FSH release. This is clinically relevant in the menstrual cycle regulation and in conditions like PCOS.

Clinical significance includes: (1) Inhibin B as a biomarker for Sertoli cell tumors and granulosa cell tumors of the ovary—elevated inhibin levels are used as tumor markers, especially in granulosa cell tumors where inhibin B/A can be dramatically elevated; (2) Inhibin B as an indicator of spermatogenic function—low levels suggest impaired spermatogenesis or Sertoli cell dysfunction, useful in male infertility workups; (3) Inhibin A is part of the quadruple screen in prenatal testing for Down syndrome (trisomy 21), where elevated maternal serum inhibin A is one of four markers (along with AFP, hCG, and estriol) suggesting increased risk—classically remembered as the only marker that is elevated (not decreased) in Down syndrome screening, distinguishing it from decreased AFP and estriol.

Understanding inhibin helps clarify the distinction between the endocrine (testosterone-driven) and paracrine (Sertoli cell-driven) feedback loops in the hypothalamic-pituitary-gonadal axis, a classic USMLE testing point.