Steroidogenic Factor 1 Regulates Transcription of the Inhibin B Coreceptor in Pituitary Gonadotrope Cells

Author:

Lin Yeu-Farn1,Schang Gauthier1,Buddle Evan R S1,Schultz Hailey2,Willis Thea L3,Ruf-Zamojski Frederique4,Zamojski Michel4,Mendelev Natalia4,Boehm Ulrich5,Sealfon Stuart C4,Andoniadou Cynthia L3,Bernard Daniel J12ORCID

Affiliation:

1. Department of Pharmacology and Therapeutics, McGill University , Montreal, Quebec H3G 1Y6 , Canada

2. Department of Anatomy and Cell Biology, McGill University , Montreal, Quebec H3A 0C7 , Canada

3. Centre for Craniofacial and Regenerative Biology, King’s College London , London SE1 1UL , UK

4. Department of Neurology, Center for Advanced Research on Diagnostic Assays, Icahn School of Medicine at Mount Sinai , New York, NY 10029 , USA

5. Department of Experimental Pharmacology, Center for Molecular Signaling, Saarland University School of Medicine , Homburg 66421 , Germany

Abstract

Abstract The inhibins control reproduction by suppressing follicle-stimulating hormone synthesis in pituitary gonadotrope cells. The newly discovered inhibin B coreceptor, TGFBR3L, is selectively and highly expressed in gonadotropes in both mice and humans. Here, we describe our initial characterization of mechanisms controlling cell-specific Tgfbr3l/TGFBR3L transcription. We identified two steroidogenic factor 1 (SF-1 or NR5A1) cis-elements in the proximal Tgfbr3l promoter in mice. SF-1 induction of murine Tgfbr3l promoter–reporter activity was inhibited by mutations in one or both sites in heterologous cells. In homologous cells, mutation of these cis-elements or depletion of endogenous SF-1 similarly decreased reporter activity. We observed nearly identical results when using a human TGFBR3L promoter–reporter. The Tgfbr3l gene was tightly compacted and Tgfbr3l mRNA expression was essentially absent in gonadotropes of SF-1 (Nr5a1) conditional knockout mice. During murine embryonic development, Tgfbr3l precedes Nr5a1 expression, though the two transcripts are fully colocalized by embryonic day 18.5 and thereafter. Collectively, these data indicate that SF-1 directly regulates Tgfbr3l/TGFBR3L transcription and is required for postnatal expression of the gene in gonadotropes.

Funder

Canadian Institute of Health Research

National Institute of Health

Medical Research Council

Canadian Institutes of Health Research

Publisher

The Endocrine Society

Subject

Endocrinology

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