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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • COS Cells
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Female
  • Follicle Stimulating Hormone / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Genotype
  • Humans
  • Polymorphism, Genetic*
  • Progesterone / metabolism
  • Receptors, FSH / genetics*
  • Receptors, FSH / metabolism
  • Signal Transduction / drug effects*

Substances

  • Receptors, FSH
  • Progesterone
  • Follicle Stimulating Hormone