Chan W Y
Department of Pediatrics, Georgetown University Children's Medical Center, Washington, DC 20007, USA.
Mol Genet Metab. 1998 Feb;63(2):75-84. doi: 10.1006/mgme.1997.2650.
Human reproductive function is regulated mainly by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Mutations of the human LH/ chorionic gonadotropin receptor (LHR) and the FSH receptor (FSHR) leading to either constitutive activation or inactivation of the receptors have been identified. All activating mutations of the LHR and the FSHR are located within the exon encoding the transmembrane domain while the inactivating mutations are scattered throughout the coding sequence. A number of activating and inactivating mutations of the LHR have been found while only one activating and three inactivating mutations of the FSHR are known. Activating mutations of the LHR cause familial male-limited precocious puberty (FMPP) while that of the FSHR has been shown to restore the reproductive capability of a hypophysectomized male. Inactivating mutations of the LHR cause Leydig cell hypoplasia (LCH) in males while that of the FSHR causes hereditary hypergonadotropic ovarian dysgenesis (ODG) in females. Activating mutations of both receptors are dominant while inactivating mutations are recessive. Genotype-phenotype correlation is best established for the inactivating mutations of LHR. Severity of clinical phenotype in LCH correlates with the amount of residual activity of the mutated LHR. Comparison of the clinical impact of the activating and the inactivating mutations of the receptors indicates that male reproductive capacity depends primarily on LH while female reproductive capacity depends primarily on FSH.
人类生殖功能主要由促黄体生成素（LH）和促卵泡生成素（FSH）调节。已鉴定出人类LH/绒毛膜促性腺激素受体（LHR）和FSH受体（FSHR）的突变，这些突变导致受体的组成性激活或失活。LHR和FSHR的所有激活突变都位于编码跨膜结构域的外显子内，而失活突变则散布在整个编码序列中。已发现许多LHR的激活和失活突变，而已知FSHR只有一个激活突变和三个失活突变。LHR的激活突变导致家族性男性限性性早熟（FMPP），而FSHR的激活突变已被证明可恢复垂体切除男性的生殖能力。LHR的失活突变导致男性睾丸间质细胞发育不全（LCH），而FSHR的失活突变导致女性遗传性高促性腺激素性卵巢发育不全（ODG）。两种受体的激活突变都是显性的，而失活突变是隐性的。LHR失活突变的基因型-表型相关性建立得最好。LCH临床表型的严重程度与突变LHR的残余活性量相关。受体激活和失活突变的临床影响比较表明，男性生殖能力主要取决于LH，而女性生殖能力主要取决于FSH。
