Endogenous Betaglycan Is Essential for High-Potency Inhibin Antagonism in Gonadotropes

Author:

Wiater Ezra1,Lewis Kathy A.1,Donaldson Cynthia1,Vaughan Joan1,Bilezikjian Louise1,Vale Wylie1

Affiliation:

1. Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, California 92037

Abstract

Abstract Inhibins are endocrine hormones that regulate gametogenesis and reproduction through a negative feedback loop with FSH. Inhibin action involves antagonism of signaling by activin or other TGFβ family ligands. In transfection assays, antagonism by inhibin can be potentiated by betaglycan, a coreceptor for selected TGFβ family ligands. We tested whether betaglycan is an obligate inhibin coreceptor through disruption of betaglycan function by RNA interference-mediated knockdown and immunoneutralization. Betaglycan knockdown and anti-betaglycan IgG each independently prevented inhibin-A binding to betaglycan and reversed functional effects of transfected betaglycan. Neither betaglycan immunoneutralization nor knockdown affected activin responsiveness in cell lines or in rat anterior pituitary cultures. Betaglycan knockdown decreased the potency of inhibin antagonism of activin-induced FSH secretion in primary gonadotropes. Similarly, anti-betaglycan IgG decreased the potency of inhibin antagonism in primary gonadotropes in a dose-dependent manner, with a reduction in the sensitivity to inhibin-A of greater than 1000-fold. These data establish that betaglycan is an endogenous inhibin coreceptor required for high-sensitivity inhibin antagonism of activin signaling in rat anterior pituitary gonadotropes.

Publisher

The Endocrine Society

Subject

Endocrinology,Molecular Biology,General Medicine

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