Casarini Livio, Moriondo Valeria, Marino Marco, Adversi Francesca, Capodanno Francesco, Grisolia Chiarina, La Marca Antonio, La Sala Giovanni Battista, Simoni Manuela
Unit of Endocrinology, Dept. of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy.
Unit of Endocrinology, Dept. of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; Center for Genome Research, University of Modena and Reggio Emilia, Modena, Italy.
Mol Cell Endocrinol. 2014 Aug 5;393(1-2):83-91. doi: 10.1016/j.mce.2014.06.013. Epub 2014 Jun 23.
The single nucleotide polymorphism p.N680S of the follicle-stimulating hormone (FSH) receptor (FSHR) is a discrete marker of ovarian response but previous in vitro studies failed to demonstrate differences in the response to FSH between N and S carrier cells. Here we demonstrate that p.N680S mediates different kinetics of the response to FSH in vitro. Intracellular cAMP production is faster in p.N680S N than in S homozygous human granulosa cells (45 versus 90 min to achieve the plateau, respectively; Mann-Whitney's U-test; p < 0.005; n = 4). Reflecting the cAMP kinetics, phospho-ERK1/2 and -CREB activation, AREG and STARD1 gene expressions and progesterone production were qualitatively and quantitatively different in N versus S homozygous cells. Finally, the blockade of ERK pathway by U0126 abolishes the genotype-mediated different effects on gene expression and progesterone production (Mann-Whitney's U-test; p ≥ 0.005; n = 3).
促卵泡激素（FSH）受体（FSHR）的单核苷酸多态性p.N680S是卵巢反应的一个离散标志物，但先前的体外研究未能证明N和S等位基因携带者细胞对FSH的反应存在差异。在此，我们证明p.N680S在体外介导了对FSH反应的不同动力学。在p.N680S N型纯合人颗粒细胞中，细胞内cAMP的产生比S型纯合细胞更快（分别为45分钟和90分钟达到平台期；曼-惠特尼U检验；p < 0.005；n = 4）。反映cAMP动力学，N型与S型纯合细胞中磷酸化ERK1/2和-CREB的激活、AREG和STARD1基因表达以及孕酮产生在定性和定量上均存在差异。最后，U0126对ERK通路的阻断消除了基因型介导的对基因表达和孕酮产生的不同影响（曼-惠特尼U检验；p≥0.005；n = 3）。
