ACTUALITIES IN MUTATIONS OF LUTEINIZING HORMONE (LH) AND FOLLICLE-STIMULATING HORMONE (FSH) RECEPTORS

Pituitary gonadotropins (FSH and LH) act through G protein coupled receptors, encoded by genes located on 2p21-p16 chromosome. FSH, LH, hCG, TSH are heterodimeric glycoprotein hormones with a common α subunit and a specific β subunit (of note, there is a 82% homology of LH with placental hCG). The gene encoding LH receptor (LHR), also known as LHCGR, has 11 exons, while the FSH receptor (FSHR) gene has 10 exons. The receptors have 3 domains: a long extracellular amino-terminal domain, a 7- loop transmembrane domain and a short carboxy-terminal intracellular domain. They work through Gαs activation and cAMP pathway, protein kinase A recruitment, extracellular-regulated kinase (ERK1/2) and cAMP-responsive element binding-protein (CREB) phosphorylation, subsequently stimulating steroidogenesis in target cells (1, 2). LHR may also activate Gq/11 and inositol triphosphate pathway (1). Gonadal expression of gonadotropin receptors. LHR is expressed in testicular Leydig cells and ovarian granulosa and thecal cells. LHR stimulates the differentiation of fetal Leydig cells and testosterone production; it is essential for male sexual maturation and spermatogenesis. LHR in women stimulates folliculogenesis, ovulation and progesterone secretion (3)