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Mol Cell Endocrinol. 2014 Aug 5;393(1-2):83-91. doi: 10.1016/j.mce.2014.06.013. Epub 2014 Jun 23.

FSHR polymorphism p.N680S mediates different responses to FSH in vitro.

Author information

1
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.
2
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.
3
Unit of Obstetrics and Gynecology, IRCCS-Arcispedale Santa Maria Nuova, Reggio Emilia, Italy.
4
Dept. of Laboratory Medicine and Pathology, Laboratory of Chemical-Clinical Analysis, University Hospital of Modena, Modena, Italy.
5
Dept. of Medical and Mother-Infant and Adult Surgical Sciences, Unit of Obstetrics and Gynecology, University Hospital of Modena, Modena, Italy.
6
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.
7
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.

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).

KEYWORDS:

FSH; FSHR; Granulosa cells; Polymorphism; p.N680S

PMID:
24970684
DOI:
10.1016/j.mce.2014.06.013
[Indexed for MEDLINE]

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