Kumar T R, Wang Y, Lu N, Matzuk M M
Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
Nat Genet. 1997 Feb;15(2):201-4. doi: 10.1038/ng0297-201.
Follicle stimulating hormone (FSH) is a member of the glycoprotein hormone family that includes luteinzing hormone (LH), thyroid stimulating hormone, and chorionic gonadotropin. These heterodimeric hormones share a common alpha subunit and differ in their hormone-specific beta subunit. The biological activity is conferred only by the heterodimers. FSH and LH are synthesized in the same cells of the pituitary, the gonadotrophs. FSH receptors are localized to Sertoli cells of the testes and granulosa cells of the ovary. Minimal data has been accumulated so far involving human mutations in the FSH beta, LH beta, or the gonadotropin receptor genes. There are no known mouse strains with mutations in the FSH beta gene. To generate animal models for human diseases involving the gonadotropin signal transduction pathway, we produced mice deficient in the FSH beta subunit and therefore in FSH using ES cell technology. FSH-deficient females are infertile due to a block in folliculogenesis prior to antral follicle formation. Although FSH was predicted to be necessary for spermatogenesis and Sertoli cell growth in males, FSH-deficient males are fertile despite having small testes. Our findings have important implications for male contraceptive development in humans.
促卵泡激素（FSH）是糖蛋白激素家族的一员，该家族还包括黄体生成素（LH）、促甲状腺激素和绒毛膜促性腺激素。这些异源二聚体激素共享一个共同的α亚基，其激素特异性β亚基有所不同。只有异源二聚体具有生物活性。FSH和LH在垂体的同一细胞即促性腺激素细胞中合成。FSH受体定位于睾丸的支持细胞和卵巢的颗粒细胞。到目前为止，关于FSHβ、LHβ或促性腺激素受体基因的人类突变积累的数据极少。目前还没有已知的FSHβ基因发生突变的小鼠品系。为了建立涉及促性腺激素信号转导途径的人类疾病动物模型，我们利用胚胎干细胞技术培育出了缺乏FSHβ亚基从而缺乏FSH的小鼠。缺乏FSH的雌性小鼠由于在窦状卵泡形成之前卵泡发生受阻而不育。尽管预计FSH对雄性精子发生和支持细胞生长是必需的，但缺乏FSH的雄性小鼠尽管睾丸较小却仍具有生育能力。我们的研究结果对人类男性避孕药物的开发具有重要意义。
