Genomic Cloning and Sequence Analyses of the Bovine α‐, β A ‐ and β B ‐Inhibin/activin Genes

Inhibins and activins are dimeric peptide hormones that regulate the circulating levels of follicle‐stimulating hormone (FSH). In turn, FSH stimulates inhibin gene expression in the ovarian follicle; studies to date suggest that this effect is mediated by cAMP and that a cAMP‐responsive element, identified in the 5′‐flanking region of the α‐inhibin gene, at least partially effects this response. To explore further the transcriptional regulation of the inhibin/activin genes, we have isolated and sequenced the 5′‐flanking regions of the bovine α‐, β A ‐ and β B ‐inhibin/activin subunit genes and have analysed these regions by primer‐extension analysis and DNase I footprinting with the transcription factor AP‐2. Analyses indicated that all three gene promoter regions have a number of AP‐2‐binding sites that are resistant to competition by poly(dI‐dC), suggesting that cAMP may control the inhibin/activin ratio by operating through alternative signal‐transduction pathways or that inhibin/activin gene expression may be controlled by signals operating through the protein kinase C pathway. A comparison of the DNA sequences protected by AP‐2 against DNase I digestion revealed a consensus AP‐2‐binding site of 5′‐GSCCCDSS‐3′, where S represents a base pairing involving three (C or G) hydrogen bonds and D represents any base other than C. The nucleotide sequences of the bovine β‐subunit structural genes also are reported.