Steroidogenic factor 1 regulates transcription of the inhibin B co-receptor in pituitary gonadotrope cells

The inhibins control reproduction by suppressing follicle-stimulating hormone synthesis by pituitary gonadotrope cells. The recently discovered inhibin B co-receptor mediating this inhibition, TGFBR3L, is selectively and highly expressed in gonadotropes in both mice and humans. We sought to characterize mechanisms controlling cell-specific Tgfbr3l/TGFBR3L transcription. We identified two steroidogenic factor 1 (SF-1) cis-elements in the proximal Tgfbr3l promoter in mice. Using single-nucleus ATAC-seq we find that gonadotrope-specific SF-1 (Nr5a1) knockout mice, which exhibit hypogonadotropic hypogonadism, display, contrary to controls, closed chromatin in the promoter region of theTgfbr3l gene in gonadotropes. These, and other, data collectively indicate that SF-1 directly regulates Tgfbr3l/TGFBR3L transcription, contributing to gonadotrope-specific expression of the gene. Overall design: Chromatin accessibility profiles of adult mouse SF-1 control and cKO pituitary gonadotrope cells were generated using Chromium Single Cell ATAC from 10X Genomics and Illumina sequencing.