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.
| Receptor | Ligand | Phenotype of loss-of-function mutations | Phenotype of gain-of-function mutations | Refs. |
| GnRHR | GnRH | nIHH | (33) | |
| KISS1R | Kisspeptin | nIHH | CPP | (22, 31, 34) |
| PROKR2 | Prokineticin | Kallmann syndrome and nIHH | (30) | |
| TACR3 | Neurokinin B | nIHH | (32) | |
| LHCGR | LH and hCG | 46,XY disturbance of sexual development (Leydig cell hypoplasia) or hypergonadotropic hypogonadism | Germline defects: FMPP or testotoxicosis Somatic defect: Leydig cell adenoma | (19, 20, 39) |
| FSHR | FSH | 46,XX gonadal dysgenesis or hypergonadotropic hypogonadism | Ovarian hyperstimulation syndrome Male gonadotropin- independent fertility | (24, 25) (38) |