Molecular pathology of the FSH receptor: New insights into FSH physiology

Abstract

Please cite this article as: Meduri, G., Bachelot, A., Cocca, M.P., Vasseur, C., Rodien, P., Kuttenn, F., Touraine, P., Misrahi, M., Molecular Pathology of the FSH receptor: new insights into FSH physiology, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2007 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

An unbalanced translocation unmasks a recessive mutation in the follicle-stimulating hormone receptor (FSHR) gene and causes FSH resistance

“…This observation suggested a limited FSH effect to be sufficient for promoting follicular growth up to the small antral stage. This is in line with Meduri et al, 19 who hypothesized the absolute requirement of FSH for follicular development starting from the primary stage in humans, in contrast to the initial gonadotrophin-independent follicular growth before the preantralearly antral stages observed in rodents.…”

“…7,9,19 In these patients, the ovaries were of normal size containing follicles developed up to the early antral stages. This observation suggested a limited FSH effect to be sufficient for promoting follicular growth up to the small antral stage.…”

“…In gain-of-function mutations, the phenotypic changes are caused by heterozygosity and dominant inheritance, whereas loss-of-function mutations are mostly transmitted recessively and need homozygosity or compound heterozygosity to cause the clinical phenotype. 19 In this study, we describe for the first time the compound heterozygous combination of a novel inactivating point mutation that was unmasked by a small partial deletion of the FSHR locus resulting clinically in a hypergonadotropic hypogonadism with primary amenorrhea.…”

Differential time course of FSH/FSH receptor complex endocytosis within sertoli and germ cells during rat testis development

“…If the structure of the FSH receptors and their role in spermatogenesis are well known (reviewed in Huhtaniemi, 2000;Meduri et al, 2008), its cellular and intracellular distribution is questionable. Previous data, using antibodies directed against the receptor peptide complex, described its presence at the plasma membrane of Sertoli cells (Dattatreyamurty and Reichert, 1993;Beau et al, 1998).…”

Spermatogenèse normale chez un homme avec défaut génétique de la LH

“…L'action conjointe de la testostérone et de la FSH s'exerce sur les cellules de Sertoli qui délimitent la paroi des tubes dique nous offre l'opportunité de mieux comprendre la physiologie humaine. Les répercussions de mutations des récep-teurs de la LH (LHR) et de la FSH, ou de leurs ligands hormonaux correspondants, ont permis d'identifier certains syndromes et de mieux comprendre l'action physiologique des hormones sur leurs organes cibles [3]. Des mutations de la LH inactivant complètement la fonction de l'hormone ont été retrouvées chez cinq patients [4][5][6][7].…”