Molecular regulation of follicle-stimulating hormone synthesis, secretion and action.
Molecular regulation of follicle-stimulating hormone synthesis, secretion and action.
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DOI：
10.1530/jme-17-0308
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发表时间：
2018-04
影响因子：
3.5
通讯作者：
Kumar TR
中科院分区：
文献类型：
--
作者：
Das N;Kumar TR
卵泡刺激素（FSH）在男性和女性生育中起着重要作用。FSH是由垂体前叶促性腺激素细胞表达的异源二聚体糖蛋白。卵泡特异性FSHβ亚基与共同α亚基非共价结合，共同α亚基也存在于促黄体激素（LH）中，促黄体激素是促性腺激素分泌的另一种促性腺激素，促甲状腺激素分泌的促甲状腺激素（TSH）。几十年的研究导致了FSH在包括人类在内的各种物种中的纯化、结构表征和生理调节。随着分子工具的出现，永生化促性腺激素细胞系和转基因小鼠模型的可用性，我们对FSH调节的分子机制的认识大大扩展。在生理环境中，已经确定了几个调节FSH合成、分选、分泌和在性腺和性腺外组织中作用的关键参与者。新的转录后和翻译后调节机制也已确定，提供额外的调节层介导FSH稳态。重组人FSH类似物有望用于各种临床应用，而针对FSH的阻断抗体可能被证明对预防年龄依赖性骨质流失和肥胖有效。预计几个令人兴奋的新发现将很快揭示FSH生物学的各个方面。
Follicle-stimulating hormone (FSH) plays fundamental roles in male and female fertility. FSH is a heterodimeric glycoprotein expressed by gonadotrophs in the anterior pituitary. The hormone-specific FSHβ-subunit is non-covalently associated with the common α-subunit that is also present in the luteinizing hormone (LH), another gonadotrophic hormone secreted by gonadotropes and thyroid-stimulating hormone (TSH) secreted by thyrotrophs. Several decades of research led to the purification, structural characterization and physiological regulation of FSH in a variety of species including humans. With the advent of molecular tools, availability of immortalized gonadotroph cell lines and genetically modified mouse models, our knowledge on molecular mechanisms of FSH regulation has tremendously expanded. Several key players that regulate FSH synthesis, sorting, secretion and action in gonads and extra-gonadal tissues have been identified in a physiological setting. Novel post-transcriptional and post-translational regulatory mechanisms have also been identified that provide additional layers of regulation mediating FSH homeostasis. Recombinant human FSH analogs hold promise for a variety of clinical applications, whereas blocking antibodies against FSH may prove efficacious for preventing age-dependent bone loss and adiposity. It is anticipated that several exciting new discoveries uncovering all aspects of FSH biology will soon be forthcoming.