TGFBR3L is an inhibin B co-receptor that regulates female fertility.
TGFBR3L is an inhibin B co-receptor that regulates female fertility.
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DOI：
10.1126/sciadv.abl4391
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发表时间：
2021-12-17
期刊：
影响因子：
13.6
通讯作者：
Bernard DJ
中科院分区：
文献类型：
--
作者：
Brûlé E;Wang Y;Li Y;Lin YF;Zhou X;Ongaro L;Alonso CAI;Buddle ERS;Schneyer AL;Byeon CH;Hinck CS;Mendelev N;Russell JP;Cowan M;Boehm U;Ruf-Zamojski F;Zamojski M;Andoniadou CL;Sealfon SC;Harrison CA;Walton KL;Hinck AP;Bernard DJ
一种新的垂体蛋白的发现表明了一种提高生育能力的新方法。促卵泡激素（FSH）是卵巢功能的关键调节因子，常用于治疗不孕症。性腺激素抑制垂体促性腺细胞合成FSH。TGFβ III型受体β聚糖是卵泡刺激素A抑制FSH所必需的。以前不知道的Escherichin B辅助受体。在这里，我们报告说，促性腺激素限制性跨膜蛋白，TGF β R 3 L，是难以捉摸的β受体B的共同受体。TGF β R 3 L结合TGF β B B，但不结合其它TGFβ家族配体。TGFBR 3 L敲低或过表达消除或赋予细胞中的TGFBR B B活性。雌性Tgfbr3l基因敲除小鼠表现出FSH水平、卵泡发育和窝仔数增加。相反，缺乏TGFBR3L和β聚糖的雌性小鼠是不育的。TGFBR3L的功能和细胞特异性表达使其成为调节FSH和生育力的有吸引力的新靶点。
Discovery of a novel pituitary protein suggests a new means to enhance fertility. 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.