2014 - FSHR polymorphism p.N680S mediates different responses to FSH in vitro Pubblicato su: Mol cell endocrinology

Casarini L1, Moriondo V2, Marino M2, Adversi F3, Capodanno F3, Grisolia C4, La Marca A5, La Sala GB6, Simoni M7. 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