The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis.

TLDR

Steroidogenic factor 1 (SF‑1) is an orphan nuclear receptor that regulates enzymes producing sex steroids, and loss of its gene Ftz‑F1 blocks adrenal and gonadal development. The study investigates SF‑1’s role at additional levels of the hypothalamic/pituitary/gonadal axis. Disruption of Ftz‑F1 in mice eliminates gonadotrope‑specific markers and transcripts, shows that SF‑1 expression precedes gonadotropin genes, colocalizes with LH in rat pituitary, and binds the glycoprotein hormone alpha‑subunit promoter, thereby revealing new roles for SF‑1 in reproductive function.

Abstract

Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, regulates the enzymes that produce sex steroids, and disruption of the Ftz-F1 gene encoding SF-1 precludes adrenal and gonadal development. We now study the role of SF-1 at other levels of the hypothalamic/pituitary/gonadal axis. In Ftz-F1-disrupted mice, immunohistochemical analyses with antibodies against pituitary trophic hormones showed a selective loss of gonadotrope-specific markers, supporting the role of SF-1 in gonadotrope function. In situ hybridization analyses confirmed these results; pituitaries from Ftz-F1-disrupted mice lacked transcripts for three gonadotrope-specific markers (LH beta, FSH beta, and the receptor for gonadotropin-releasing hormone), whereas they exhibited decreased but detectable expression of the alpha-subunit of glycoprotein hormones. SF-1 transcripts in the developing mouse pituitary, which first became detectable at embryonic day 13.5-14.5, preceded the appearance of FSH beta and LH beta transcripts. In adult rat pituitary cells, SF-1 transcripts colocalized with immunoreactivity for the gonadotrope-specific LH. Finally, SF-1 interacted with a previously defined promoter element in the glycoprotein hormone alpha-subunit gene, providing a possible mechanism for the impaired gonadotropin expression in Ftz-F1-disrupted mice. These studies establish novel roles of this orphan nuclear receptor in reproductive function.