Suzuki Erina, Miyado Mami, Kuroki Yoko, Fukami Maki
Department of Molecular Endocrinology National Research Institute for Child Health and Development Tokyo Japan.
Department of Food and Nutrition Beppu University Oita Japan.
Reprod Med Biol. 2023 Apr 27;22(1):e12515. doi: 10.1002/rmb2.12515. eCollection 2023 Jan-Dec.
The human hypothalamic-pituitary-gonadal (HPG) axis is the regulatory center for pubertal development. This axis involves six G-protein coupled receptors (GPCRs) encoded by , , , , , and .
Previous studies have identified several rare variants of the six GPCR genes in patients with pubertal disorders. In vitro assays and animal studies have provided information on the function of wild-type and variant GPCRs.
Of the six GPCRs, those encoded by and are likely to reside at the top of the HPG axis. Several loss-of-function variants in the six genes were shown to cause late/absent puberty. In particular, variants in , , , and lead to hypogonadotropic hypogonadism in autosomal dominant, recessive, and oligogenic manners. Furthermore, a few gain-of-function variants of , , and have been implicated in precocious puberty. The human HPG axis may contain additional GPCRs.
The six GPCRs in the HPG axis govern pubertal development through fine-tuning of hormone secretion. Rare sequence variants in these genes jointly account for a certain percentage of genetic causes of pubertal disorders. Still, much remains to be clarified about the molecular network involving the six GPCRs.
人类下丘脑 - 垂体 - 性腺（HPG）轴是青春期发育的调节中心。该轴涉及由、、、、和编码的六种G蛋白偶联受体（GPCR）。
先前的研究已经在青春期障碍患者中鉴定出六种GPCR基因的几种罕见变体。体外试验和动物研究提供了关于野生型和变体GPCR功能的信息。
在六种GPCR中，由和编码的那些可能位于HPG轴的顶端。六个基因中的几个功能丧失变体被证明会导致青春期延迟/缺失。特别是，、、和中的变体以常染色体显性、隐性和寡基因方式导致低促性腺激素性性腺功能减退。此外，、和的一些功能获得变体与性早熟有关。人类HPG轴可能包含其他GPCR。
HPG轴中的六种GPCR通过微调激素分泌来控制青春期发育。这些基因中的罕见序列变体共同构成了青春期障碍遗传原因的一定比例。然而，关于涉及这六种GPCR的分子网络仍有许多有待阐明的地方。
