An Upgrade in the Processor

Science Signaling  02 Dec 2008:
Vol. 1, Issue 48, pp. ec413
DOI: 10.1126/scisignal.148ec413

Inhibin and activin are ligands in the transforming growth factor-β (TGF-β) family that exert opposing actions on the biosynthesis and release of follicle-stimulating hormone from the anterior pituitary. They share a common β subunit: Activin is a dimer of these β subunits, whereas inhibin contains an α subunit in addition to the β subunit. Antenos et al. found that activin treatment of pituitary LβT2 cells increased accumulation of α and β subunit mRNAs, production of precursor and mature α and β subunits, and secretion of activin and inhibin dimers. Both activin and inhibin are cleaved from large precursor proteins by proprotein convertases; after identifying furin as one of the key proprotein convertases that cleave inhibin precursors, the authors showed that activin treatment of LβT2 cells triggered production of furin mRNA through a pathway that involved the TGF-β-receptor activated transcription factors Smad2 and Smad3. None of the other TGF-β ligands tested, including inhibin, activated transcription of the furin gene. This short positive feedback loop between activin treatment and secretion of both activin and its opposing hormone, inhibin, led the authors to propose that activin and inhibin processing may be as critical to determining the activity of these TGF-β ligands as expression patterns or secretion dynamics.

M. Antenos, J. Zhu, N. M. Jetly, T. K. Woodruff, An activin/furin regulatory loop modulates the processing and secretion of inhibin α- and βB-subunit dimers in pituitary gonadotrope cells. J. Biol. Chem. 283, 33059–33068 (2008). [Abstract] [Full Text]