A Tale of Two Proteins: Betaglycan, IGSF1, and the Continuing Search for the Inhibin B Receptor

Trends Endocrinol Metab. 2020 Jan;31(1):37-45. doi: 10.1016/j.tem.2019.08.014. Epub 2019 Oct 22.

Abstract

Inhibins are gonadal hormones that suppress follicle-stimulating hormone (FSH) synthesis by pituitary gonadotrope cells. The structurally related activins stimulate FSH by signaling through complexes of type I and type II receptors. Two models of inhibin action were proposed in 2000. First, inhibins function as competitive receptor antagonists, binding activin type II receptors with high affinity in the presence of the TGF-β type III coreceptor, betaglycan. Second, immunoglobulin superfamily, member 1 (IGSF1, then called p120) was proposed to mediate inhibin B antagonism of activin signaling via its type I receptor. These ideas have been challenged over the past few years. Rather than playing a role in inhibin action, IGSF1 is involved in the central control of the thyroid gland. Betaglycan binds inhibin A and inhibin B with high affinity, but only functions as an obligate inhibin A coreceptor in murine gonadotropes. There is likely to be a distinct, but currently unidentified coreceptor for inhibin B.

Keywords: activin; follicle-stimulating hormone; inhibin; pituitary.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism*
  • Inhibins / genetics
  • Inhibins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Pituitary Gland / metabolism*
  • Protein Binding
  • Proteoglycans / metabolism*
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • IGSF1 protein, human
  • Immunoglobulins
  • Membrane Proteins
  • Proteoglycans
  • Receptors, Transforming Growth Factor beta
  • betaglycan
  • Inhibins