An activin/furin regulatory loop modulates the processing and secretion of inhibin α- and βB-subunit dimers in pituitary gonadotrope cells

Monica Antenos, Jie Zhu, Niti M. Jetly, Teresa K. Woodruff

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Of all ligands of the transforming growth factor β superfamily, inhibins and activins are a physiologically relevant pair that are functional antagonists of each other. Activin stimulates whereas inhibin blocks follicle-stimulating hormone biosynthesis and secretion from pituitary gonadotrope cells, and together, inhibin and activin control the pituitary gonadal axis essential for normal reproductive function. Sharing a similar β-subunit, the secretion of inhibin heterodimers (α/β) or activin homodimers (β/β) as mature bioactive ligands depends, in part, on the proteolytic processing of precursor proteins.Ashort loop regulatory pathway controlling precursor processing and dimer secretion was discovered. Activin stimulates endogenous inhibin α- and βB-subunit mRNA, protein, and proteolytic processing. Simultaneously, activin stimulated the proconvertase furin through a Smad2/3-dependent process. The data provide a mechanism where the regulation of furin and inhibin subunits cooperates in an important positive short feedback loop. This regulatory loop augments the secretion of bioactive mature activin B, as well as inhibin B dimers, necessary for local follicle-stimulating hormone β regulation.

Original languageEnglish (US)
Pages (from-to)33059-33068
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number48
DOIs
StatePublished - Nov 28 2008

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'An activin/furin regulatory loop modulates the processing and secretion of inhibin α- and β<sub>B</sub>-subunit dimers in pituitary gonadotrope cells'. Together they form a unique fingerprint.

Cite this