卵泡刺激素受体：进展和挑战
Follicle-stimulating hormone receptor: Advances and remaining challenges
摘要：
促卵泡激素（FSH）是在脑垂体中产生的，对生殖至关重要。它特异性结合在性腺体细胞中表达的膜受体（FSHR）。FSH/FSHR系统与经典的G蛋白偶联受体（GPCR）相比具有许多特性。FSH是一种大的天然异质异二聚体糖蛋白。FSHR的特征在于非常大的NH 2-末端胞外结构域，其结合FSH并参与受体的激活/失活开关。一旦激活，FSHR与Gα结合，在某些情况下，与其他Gα亚基结合。G蛋白偶联受体激酶和β-抑制蛋白也被募集到FSHR中，并负责其脱敏、控制其运输和细胞内信号传导。值得注意的是，FSHR内化和再循环非常快，并且涉及非常早期的内体而不是早期的内体。FSH刺激后触发的所有转导机制导致复杂信号网络的激活，该网络通过在多个水平上起作用来控制基因表达。这些机制的整合导致目标性腺细胞的适应性反应，但也间接影响生殖细胞的命运。根据生理/发育阶段，FSH促进增殖、分化或凋亡，以维持生殖系统的稳态。针对FSHR的药理学工具最近脱颖而出，为基础研究和治疗应用开辟了广阔的前景。本文提供了一个最新的审查最突出的方面和特点FSHR生物学和药理学。
英文摘要：
Follicle-stimulating hormone (FSH) is produced in the pituitary and is essential for reproduction. It specifically binds to a membrane receptor (FSHR) expressed in somatic cells of the gonads. The FSH/FSHR system presents many peculiarities compared to classical G protein-coupled receptors (GPCRs). FSH is a large naturally heterogeneous heterodimeric glycoprotein. The FSHR is characterized by a very large NH2-terminal extracellular domain, which binds the FSH and participates to the activation/inactivation switch of the receptor. Once activated, the FSHR couples to Gαs and, in some instances, to other Gα subunits. G protein-coupled receptor kinases and β-arrestins are also recruited to the FSHR and account for its desensitization, the control of its trafficking and its intracellular signalling. Of note, the FSHR internalization and recycling are very fast and involve very early endosomes instead of early endosomes. All the transduction mechanisms triggered upon FSH stimulation lead to the activation of a complex signalling network that controls gene expression by acting at multiple levels. The integration of these mechanisms leads to context-adapted responses from the target gonadal cells, but also indirectly affects the fate of germ cells. Depending of the physiological/developmental stage, FSH elicits proliferation, differentiation or apoptosis in order to maintain the homeostasis of the reproductive system. Pharmacological tools targeting FSHR recently came to the fore and open promising prospects both for basic research and therapeutic applications. This paper provides an updated review of the most salient aspects and peculiarities of FSHR biology and pharmacology.
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