ABSTRACT
The gonadotropin-releasing hormone receptor (GnRHR) is a guanine nucleotide-binding
protein-coupled receptor with a characteristic seven transmembrane domain motif. It
transduces the hypothalamic message carried by the decapeptide gonadotropin-releasing
hormone. At the gonadotrope cell surface the hormone binds to the receptor, leading
to pituitary synthesis and secretion of gonadotropins. These glycoprotein hormones,
in turn, modulate folliculogenesis and ovulation in the ovary. Failure of the GnRHR
to respond appropriately to its cognate ligand has been demonstrated in humans. These
patients have genomic mutations in the gene for the GnRHR and represent the first
individuals with hypogonadotropic hypogonadism of autosomal inheritance. The mutant
receptors are poorly expressed at the cell surface and have a diminished capacity
to transduce the hypothalamic message efficiently. To date, no mutations have been
identified that lead to constitutively active receptors and autonomous gonadotropin
function. This article identifies the mutations in the GnRHR reported to date and
reviews how these abnormal receptors help us to better understand the biology of this
interesting molecule.
KEYWORD
receptor - hypogonadotropic hypogonadism - delayed puberty - autosomal recessive mutations
- infertility
