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Abstract

Activins regulate 17ß-hydroxysteroid dehydrogenase type I transcription in murine gonadotrope cells (PDF) (HTML) 
Bak,Beata; Carpio,Laura; Kipp,Jinjing L.; Lamba,Pankaj; Wang,Ying; Ge,Renshan; Hardy,Matthew P.; Mayo,Kelly E.; Bernard,Daniel J.
Journal of Endocrinology 201(1): 89-104
Publication date: 2009

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Activins are pleiotropic members of the TGFß superfamilyand were initially characterized based on their abilities tostimulate FSH synthesis and secretion by gonadotrope cells ofthe anterior pituitary gland. Here, we identified the gene encodingthe steroidogenic enzyme, 17ß-hydroxysteroid dehydrogenasetype I (17ß-HSD1; Hsd17b1), as an activin-responsive genein immortalized gonadotrope cells, LßT2. 17ß-HSD1catalyzes the conversion of estrone to the more active 17ß-estradiol,and activin A stimulated an increase in this enzymatic activityin these cells. We demonstrated that activins signaled via thetype I receptor, activin receptor-like kinase (ALK4), and theintracellular signaling protein, SMAD2, to regulate Hsd17b1transcription in immediate-early fashion. Critical cis-elements,including a minimal SMAD-binding element, were mapped to within100 bp of the start of transcription. Activin/ALK4 signalingalso regulated Hsd17b1 transcription in both immortalized andprimary cultured murine granulosa cells. The promoter regionsmediating basal and activin/ALK4-regulated promoter activitywere generally conserved across the different cell types. Thedata show that activin A rapidly regulates Hsd17b1 transcriptionin gonadotrope and granulosa cells and may thereby regulatelocal 17ß-estradiol synthesis.

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