Inactivating Mutations of the Human Luteinizing Hormone Receptor in Both Sexes
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
01/11/2013
01/11/2013
2012
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Resumo |
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. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [05/04726-0] Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [300982/2009-7, 300469/2005] Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) |
Identificador |
SEMINARS IN REPRODUCTIVE MEDICINE, NEW YORK, v. 30, n. 5, supl. 1, Part 3, pp. 382-386, SEP, 2012 1526-8004 http://www.producao.usp.br/handle/BDPI/37700 10.1055/s-0032-1324721 |
Idioma(s) |
eng |
Publicador |
THIEME MEDICAL PUBL INC NEW YORK |
Relação |
SEMINARS IN REPRODUCTIVE MEDICINE |
Direitos |
closedAccess Copyright THIEME MEDICAL PUBL INC |
Palavras-Chave | #LH RECEPTOR #LEYDIG CELL HYPOPLASIA #AMENORRHEA #INFERTILITY #EMPTY-FOLLICLE-SYNDROME #LEYDIG-CELL HYPOPLASIA #HUMAN CHORIONIC-GONADOTROPIN #MALE PSEUDOHERMAPHRODITISM #MISSENSE MUTATION #OVARIAN RESISTANCE #MALE HYPOGONADISM #GENE #LH #PHENOTYPE #OBSTETRICS & GYNECOLOGY #REPRODUCTIVE BIOLOGY |
Tipo |
article original article publishedVersion |