HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: JOE-08-0460v1 201/1/89    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bak, B. Articles by Bernard, D. J Search for Related Content PubMed PubMed Citation Articles by Bak, B. Articles by Bernard, D. J

Beata Bak^*, Laura Carpio^*, Jinjing L Kipp¹, Pankaj Lamba, Ying Wang, Ren-Shan Ge², Matthew P Hardy^2,, Kelly E Mayo¹

Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Room 1315, Montreal, QC, Canada H3G 1Y6¹ Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA² Center for Biomedical Research, Population Council, New York, New York 10021, USA

(Correspondence should be addressed to D J Bernard; Email: daniel.bernard{at}mcgill.ca)

^* (B Bak and L Carpio contributed equally to this work)

MPH is now deceased

Activins are pleiotropic members of the TGFβ superfamily and were initially characterized based on their abilities to stimulate FSH synthesis and secretion by gonadotrope cells of the anterior pituitary gland. Here, we identified the gene encoding the steroidogenic enzyme, 17β-hydroxysteroid dehydrogenase type I (17β-HSD1; Hsd17b1), as an activin-responsive gene in immortalized gonadotrope cells, LβT2. 17β-HSD1 catalyzes the conversion of estrone to the more active 17β-estradiol, and activin A stimulated an increase in this enzymatic activity in these cells. We demonstrated that activins signaled via the type I receptor, activin receptor-like kinase (ALK4), and the intracellular signaling protein, SMAD2, to regulate Hsd17b1 transcription in immediate-early fashion. Critical cis-elements, including a minimal SMAD-binding element, were mapped to within 100 bp of the start of transcription. Activin/ALK4 signaling also regulated Hsd17b1 transcription in both immortalized and primary cultured murine granulosa cells. The promoter regions mediating basal and activin/ALK4-regulated promoter activity were generally conserved across the different cell types. The data show that activin A rapidly regulates Hsd17b1 transcription in gonadotrope and granulosa cells and may thereby regulate local 17β-estradiol synthesis.