Table 2

GPCRs and their ligands implicated in pubertal disorders. GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; hCG, human chorionic gonadotropin; FSH, follicle-stimulating hormone; nIHH, normosmic hypogonadotropic hypogonadism; CPP, central precocious puberty; FMPP, familial male-limited precocious puberty.

ReceptorLigandPhenotype of loss-of-function mutationsPhenotype of gain-of-function mutationsRefs.
GnRHRGnRHnIHH(33)
KISS1RKisspeptinnIHHCPP(22, 31, 34)
PROKR2ProkineticinKallmann syndrome and nIHH(30)
TACR3Neurokinin BnIHH(32)
LHCGRLH and hCG46,XY disturbance of sexual development (Leydig cell hypoplasia) or hypergonadotropic hypogonadismGermline defects: FMPP
or testotoxicosis
Somatic defect: Leydig cell adenoma
(19, 20, 39)
FSHRFSH46,XX gonadal dysgenesis or hypergonadotropic hypogonadismOvarian hyperstimulation syndrome
Male gonadotropin- independent fertility
(24, 25)
(38)