Riccetti Laura, Sperduti Samantha, Lazzaretti Clara, Casarini Livio, Simoni Manuela
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy -
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Minerva Ginecol. 2018 Oct;70(5):516-524. doi: 10.23736/S0026-4784.18.04282-X. Epub 2018 Aug 28.
Pituitary gonadotropins, follicle-stimulating (FSH) and luteinizing hormone (LH) promote follicular recruitment and support antral follicle growth, maturation and selection, resulting in ovulation of the dominant follicle. FSH and LH biological functions are mediated by G protein-coupled receptors, FSHR and LHCGR, resulting in the activation of a number of signaling cascades, such as the cyclic AMP/protein kinase A (cAMP/PKA) pathway. Some in-vitro data are consistent with the dual, proliferative and pro-apoptotic role of cAMP, leaving unanswered questions on how cAMP/PKA signaling is linked to the follicle fate. Progression of the antral stage is characterized by the presence of dynamic serum gonadotropin and estrogen levels, accompanying proliferation and steroidogenesis of growing as well as apoptosis of atretic follicles. These events are parallel to changes of FSHR and LHCGR density at the cell surface occurring throughout the antral stage, reasonably modulating the cAMP/PKA activation pattern, cell metabolism and functions. Understanding whether gonadotropins and receptor expression levels impact on the steroidogenic pathway and play a role in determining the follicular fate, may put new light on molecular mechanisms regulating human reproduction. The aim of the present review is to update the role of major players modulating the cAMP/PKA pathway and regulating the balance between proliferative, differentiating and pro-apoptotic signals.
垂体促性腺激素，即促卵泡生成素（FSH）和促黄体生成素（LH），促进卵泡募集，并支持窦卵泡的生长、成熟和选择，从而导致优势卵泡排卵。FSH和LH的生物学功能由G蛋白偶联受体FSHR和LHCGR介导，从而激活一系列信号级联反应，如环磷酸腺苷/蛋白激酶A（cAMP/PKA）途径。一些体外实验数据与cAMP的双重作用，即增殖和促凋亡作用相一致，这使得cAMP/PKA信号如何与卵泡命运相关联的问题仍未得到解答。窦卵泡期的进展特点是血清促性腺激素和雌激素水平动态变化，同时伴随着生长卵泡的增殖、类固醇生成以及闭锁卵泡的凋亡。这些事件与整个窦卵泡期细胞表面FSHR和LHCGR密度的变化平行，合理地调节cAMP/PKA激活模式、细胞代谢和功能。了解促性腺激素和受体表达水平是否会影响类固醇生成途径并在决定卵泡命运中发挥作用，可能会为调节人类生殖的分子机制带来新的启示。本综述的目的是更新调节cAMP/PKA途径并调节增殖、分化和促凋亡信号之间平衡的主要因素的作用。
