TGFBR3L is an inhibin B co-receptor that regulates female fertility.
Emilie BrûléYing WangYining LiYeu-Farn LinXiang ZhouLuisina OngaroCarlos A I AlonsoEvan R S BuddleAlan L SchneyerChang Hyeock ByeonCynthia S HinckNatalia MendelevJohn P RussellMitra CowanUlrich BoehmFrederique Ruf ZamojskiMichel ZamojskiCynthia Lilian AndoniadouStuart C SealfonCraig A HarrisonKelly L WaltonAndrew P HinckDaniel J BernardPublished in: Science advances (2021)
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 Tgfbr3l 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.
Keyphrases
- induced apoptosis
- binding protein
- cell cycle arrest
- type iii
- transforming growth factor
- cell proliferation
- single cell
- oxidative stress
- magnetic resonance imaging
- polycystic ovary syndrome
- metabolic syndrome
- cell death
- cell therapy
- computed tomography
- stem cells
- adipose tissue
- mesenchymal stem cells
- amino acid
- epithelial mesenchymal transition
- protein protein