TGFBR3L is an inhibin B co-receptor that regulates female fertility.

Brûlé, Emilie; Wang, Ying; Li, Yining; Lin, Yeu-Farn; Zhou, Xiang; Ongaro, Luisina; Alonso, Carlos A I; Buddle, Evan R S et al. · Sci Adv · 2021

basic_science · Level V

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Abstract

Follicle-stimulating hormone (FSH), a key regulator of ovarian function, is often used in infertility treatment. Gonadal inhibins suppress FSH synthesis by pituitary gonadotrope cells. The TGFβ type III receptor, betaglycan, is required for inhibin A suppression of FSH. The inhibin B co-receptor was previously unknown. Here, we report that the gonadotrope-restricted transmembrane protein, TGFBR3L, is the elusive inhibin B co-receptor. TGFBR3L binds inhibin B but not other TGFβ family ligands. TGFBR3L knockdown or overexpression abrogates or confers inhibin B activity in cells. Female <i>Tgfbr3l</i> knockout mice exhibit increased FSH levels, ovarian follicle development, and litter sizes. In contrast, female mice lacking both TGFBR3L and betaglycan are infertile. TGFBR3L’s function and cell-specific expression make it an attractive new target for the regulation of FSH and fertility.