Wu S M, Leschek E W, Rennert O M, Chan W Y
Departments of Pediatrics, Cell Biology, Biochemistry and Molecular Biology, Georgetown University Children's Medical Center, Washington, DC 20007, USA.
Front Biosci. 2000 Mar 1;5:D343-52. doi: 10.2741/wu.
Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.
人类男性性发育受绒毛膜促性腺激素（CG）和促黄体生成素（LH）调节。已报道了由人类促黄体生成素受体（LHR）激活和失活突变引起的异常性发育。所有已知的LHR激活突变都是由单碱基替换引起的错义突变。最常见的激活突变是由于核苷酸位置1733处的A被G替换，导致第578位的天冬氨酸被甘氨酸取代。所有激活突变都存在于编码受体跨膜结构域的第11外显子中。LHR的组成性活性导致男孩出现不依赖促黄体生成素释放激素的性早熟以及常染色体显性疾病家族性男性性早熟（FMPP）。在睾丸肿瘤患者中发现了LHR的种系和体细胞激活突变。激活突变对女性没有影响。LHR失活突变的分子遗传学更具多样性，包括单碱基替换、部分基因缺失和插入。这些突变并不局限于特定区域，存在于受体的细胞外和跨膜结构域中。LHR失活会导致常染色体隐性疾病莱迪希细胞发育不全（LCH）以及男性性腺功能减退或男性假两性畸形。LCH患者临床表型的严重程度与突变受体的残余活性量相关。女性受LHR失活突变的影响较小。LHR纯合失活突变引起的症状包括多囊卵巢和原发性闭经。
