Clinical and molecular genetics of the human GnRH receptor.
A functional GnRH receptor (GnRH-R) in the anterior pituitary is critical for normal LH/FSH secretion, pubertal development and reproduction. Inactivating mutations of the GnRH-R have been identified in patients with idiopathic hypogonadotrophic hypogonadism. In this article we summarize phenotypic characteristics of these patients and focus on specific functional alterations of the human GnRH-R. In-vitro studies using recombinant receptor constructs demonstrate that GnRH-R missense mutations result in impaired ligand binding and reduced signal transduction, causing gonadotrophin deficiency. A detailed molecular understanding of receptor inactivation may help to design new GnRH agonists to therapeutically modulate GnRH-R function.
Karges
Beate
B
Pediatric Endocrinology, University Children's Hospital, University of Ulm, 89075 Ulm, Germany. beate.karges@medizin.uni-ulm.de
Karges
Wolfram
W
de Roux
Nicolas
N
D000026:Abortion, Habitual / Q000235:genetics; D000022:Abortion, Spontaneous / Q000235:genetics; D002874:Chromosome Mapping; D005260:Female; D005838:Genotype; D018095:Germ-Line Mutation; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000235:genetics* / Q000628:therapy; D007248:Infertility, Male / Q000235:genetics; D008024:Ligands; D008297:Male; D008967:Molecular Biology; D009154:Mutation / Q000502:physiology; D010641:Phenotype; D011966:Receptors, LHRH / Q000235:genetics* / Q000378:metabolism; D012098:Reproduction / Q000235:genetics; D015398:Signal Transduction
D008024:Ligands; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone