title: FSHR polymorphism p.N680S mediates different responses to FSH in vitro.
abstract: 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).
authors: 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. Electronic address: livio.casarini@unimore.it.
authors: Livio
authors: L
authors: Casarini
authors: 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.
authors: Valeria
authors: V
authors: Moriondo
authors: 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.
authors: Marco
authors: M
authors: Marino
authors: Unit of Obstetrics and Gynecology, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors: Francesca
authors: F
authors: Adversi
authors: Unit of Obstetrics and Gynecology, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
authors: Francesco
authors: F
authors: Capodanno
authors: Dept. of Laboratory Medicine and Pathology, Laboratory of Chemical-Clinical Analysis, University Hospital of Modena, Modena, Italy.
authors: Chiarina
authors: C
authors: Grisolia
authors: Dept. of Medical and Mother-Infant and Adult Surgical Sciences, Unit of Obstetrics and Gynecology, University Hospital of Modena, Modena, Italy.
authors: Antonio
authors: A
authors: La Marca
authors: Unit of Obstetrics and Gynecology, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy; Dept. of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Reggio Emilia, Italy.
authors: Giovanni Battista
authors: GB
authors: La Sala
authors: 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; Azienda USL, Modena, Italy.
authors: Manuela
authors: M
authors: Simoni
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005838:Genotype; D006801:Humans; D011110:Polymorphism, Genetic; D011374:Progesterone / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D011962:Receptors, FSH; D011374:Progesterone; D005640:Follicle Stimulating Hormone
keywords: FSH; FSHR; Granulosa cells; Polymorphism; p.N680S