Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Hospital das Clinicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Semin Reprod Med. 2012 Oct;30(5):382-6. doi: 10.1055/s-0032-1324721. Epub 2012 Oct 8.
The human luteinizing hormone/chorionic gonadotropin receptor (LHCGR) plays a fundamental role in male and female reproductive physiology. Over the past 15 years, several homozygous or compound heterozygous loss-of-function mutations in the LHCGR gene have been described in males and females. In genetic males, mutations in LHCGR were associated with distinct degrees of impairment in pre- and postnatal testosterone secretion resulting in a phenotypic spectrum. Patients with the severe form of LH resistance have predominantly female external genitalia and absence of secondary sex differentiation at puberty. Patients with milder forms have predominantly male external genitalia with micropenis and/or hypospadias or only infertility without ambiguity. The undermasculization is associated with low basal, as well as human CG-stimulated, testosterone levels and elevated LH levels after pubertal age, without abnormal step-up in testosterone biosynthesis precursors. The testes have only slightly reduced size but mature Leydig cells are absent or scarce (Leydig cell hypoplasia). Genetic females with inactivating LHCGR mutations have female external genitalia, spontaneous breast and pubic hair development at puberty, and normal or late menarche followed by oligoamenorrhea and infertility. Estradiol and progesterone levels are normal for the early to midfollicular phase, but do not reach ovulatory or luteal phase levels. Serum LH levels are high whereas follicle-stimulating hormone levels are normal or only slightly increased. Pelvic ultrasound has demonstrated a small or normal uterus and normal or enlarged ovaries with cysts. The inactivating mutations of the LHCGR have provided important insights into distinct physiological roles of LH in reproduction of both sexes.
人类促黄体生成素/绒毛膜促性腺激素受体（LHCGR）在男性和女性生殖生理学中起着至关重要的作用。在过去的 15 年中，已经在男性和女性中描述了 LHCGR 基因的几种纯合子或复合杂合子功能丧失突变。在遗传男性中，LHCGR 突变与产前和产后睾酮分泌的不同程度损害相关，导致表型谱。具有 LH 抵抗严重形式的患者具有主要的女性外生殖器，并且青春期时没有第二性征分化。具有较轻微形式的患者具有主要的男性外生殖器，伴有小阴茎和/或尿道下裂，或仅不育而无模糊性。去男性化与基础和人绒毛膜促性腺激素刺激后的睾酮水平降低以及青春期后 LH 水平升高有关，没有异常的睾酮生物合成前体升高。睾丸仅略有缩小，但成熟的睾丸间质细胞缺失或稀少（睾丸间质细胞发育不良）。具有失活 LHCGR 突变的遗传女性具有女性外生殖器，青春期自发性乳房和阴毛发育，正常或晚期初潮，随后出现少经和不孕。雌二醇和孕酮水平在早卵泡期正常，但达不到排卵或黄体期水平。血清 LH 水平升高，而卵泡刺激素水平正常或仅略有升高。盆腔超声显示子宫小或正常，卵巢正常或增大，有囊肿。LHCGR 的失活突变为 LH 在两性生殖中的不同生理作用提供了重要的见解。
