Inactivating Mutations of the Human Luteinizing Hormone Receptor in Both Sexes

Página do item simplificado
dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorLATRONICO, Ana Claudia
dc.contributor.authorARNHOLD, Ivo J. P.
dc.date.accessioned2013-07-30T14:41:59Z
dc.date.available2013-07-30T14:41:59Z
dc.date.issued2012
dc.description.abstractThe 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.
dc.description.indexMEDLINE
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [05/04726-0]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [300982/2009-7, 300469/2005]
dc.identifier.citationSEMINARS IN REPRODUCTIVE MEDICINE, v.30, n.5, p.382-386, 2012
dc.identifier.doi10.1055/s-0032-1324721
dc.identifier.issn1526-8004
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/512
dc.language.isoeng
dc.publisherTHIEME MEDICAL PUBL INC
dc.relation.ispartofSeminars in Reproductive Medicine
dc.rightsrestrictedAccess
dc.rights.holderCopyright THIEME MEDICAL PUBL INC
dc.subjectLH receptor
dc.subjectamenorrhea
dc.subjectinfertility
dc.subject.otherempty-follicle-syndrome
dc.subject.otherleydig-cell hypoplasia
dc.subject.otherhuman chorionic-gonadotropin
dc.subject.othermale pseudohermaphroditism
dc.subject.othermissense mutation
dc.subject.otherovarian resistance
dc.subject.othermale hypogonadism
dc.subject.othergene
dc.subject.otherlh
dc.subject.otherphenotype
dc.subject.wosObstetrics & Gynecology
dc.subject.wosReproductive Biology
dc.titleInactivating Mutations of the Human Luteinizing Hormone Receptor in Both Sexes
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.citation.scopus43
hcfmusp.contributor.author-fmusphcANA CLAUDIA LATRONICO XAVIER
hcfmusp.contributor.author-fmusphcIVO JORGE PRADO ARNHOLD
hcfmusp.description.beginpage382
hcfmusp.description.endpage386
hcfmusp.description.issue5
hcfmusp.description.volume30
hcfmusp.lim.ref2012
hcfmusp.origemWOS
hcfmusp.origem.pubmed23044874
hcfmusp.origem.scopus2-s2.0-84866973513
hcfmusp.origem.wosWOS:000309018300007
hcfmusp.publisher.cityNEW YORK
hcfmusp.publisher.countryUSA
hcfmusp.relation.referenceArnhold IJP, 1999, CLIN ENDOCRINOL, V51, P701, DOI 10.1046/j.1365-2265.1999.00863.x
hcfmusp.relation.referenceAscoli M, 2002, ENDOCR REV, V23, P141, DOI 10.1210/er.23.2.141
hcfmusp.relation.referenceBERTHEZENE F, 1976, NEW ENGL J MED, V295, P969, DOI 10.1056/NEJM197610282951801
hcfmusp.relation.referenceBruysters M, 2008, HUM REPROD, V23, P1917, DOI 10.1093/humrep/den180
hcfmusp.relation.referenceGromoll J, 2000, J CLIN ENDOCR METAB, V85, P2281, DOI 10.1210/jc.85.6.2281
hcfmusp.relation.referenceHuhtaniemi I, 2006, BEST PRACT RES CL EN, V20, P561, DOI 10.1016/j.beem.2006.09.003
hcfmusp.relation.referenceKossack N, 2008, PLOS MED, V5, P669, DOI 10.1371/journal.pmed.0050088
hcfmusp.relation.referenceKREMER H, 1995, NAT GENET, V9, P160, DOI 10.1038/ng0295-160
hcfmusp.relation.referenceLatronico AC, 1996, NEW ENGL J MED, V334, P507, DOI 10.1056/NEJM199602223340805
hcfmusp.relation.referenceLatronico AC, 1999, AM J HUM GENET, V65, P949, DOI 10.1086/302602
hcfmusp.relation.referenceLatronico AC, 1998, MOL ENDOCRINOL, V12, P442, DOI 10.1210/me.12.3.442
hcfmusp.relation.referenceLAUE L, 1995, HUM MOL GENET, V4, P1429, DOI 10.1093/hmg/4.8.1429
hcfmusp.relation.referenceLaue LL, 1996, MOL ENDOCRINOL, V10, P987, DOI 10.1210/me.10.8.987
hcfmusp.relation.referenceLei ZM, 2001, MOL ENDOCRINOL, V15, P184, DOI 10.1210/me.15.1.184
hcfmusp.relation.referenceMartens JWM, 1998, MOL ENDOCRINOL, V12, P775, DOI 10.1210/me.12.6.775
hcfmusp.relation.referenceMisrahi M, 1997, J CLIN ENDOCR METAB, V82, P2159, DOI 10.1210/jc.82.7.2159
hcfmusp.relation.referenceMuller T, 2003, J CLIN ENDOCR METAB, V88, P2242, DOI 10.1210/jc.2002-021946
hcfmusp.relation.referenceOnalan G, 2003, HUM REPROD, V18, P1864, DOI 10.1093/humrep/deg371
hcfmusp.relation.referenceQiao J, 2009, HUM MUTAT, V30, pE855, DOI 10.1002/humu.21072
hcfmusp.relation.referenceRichard N, 2011, ENDOCR J, V58, P769
hcfmusp.relation.referenceSegaloff DL, 2009, PROG MOL BIOL TRANSL, V89, P97, DOI 10.1016/S1877-1173(09)89004-2
hcfmusp.relation.referenceStavrou SS, 1998, J CLIN ENDOCR METAB, V83, P2091, DOI 10.1210/jc.83.6.2091
hcfmusp.relation.referenceThemmen APN, 2005, REPRODUCTION, V130, P263, DOI 10.1530/rep.1.00663
hcfmusp.relation.referenceToledo SPA, 1996, J CLIN ENDOCR METAB, V81, P3850, DOI 10.1210/jc.81.11.3850
hcfmusp.relation.referenceVujisic S, 2005, HUM REPROD, V20, P2552, DOI 10.1093/humrep/dei083
hcfmusp.relation.referenceYariz KO, 2011, FERTIL STERIL, V96, pE125, DOI 10.1016/j.fertnstert.2011.05.057
hcfmusp.relation.referenceZhang FP, 2001, MOL ENDOCRINOL, V15, P172, DOI 10.1210/me.15.1.172
hcfmusp.relation.referenceZreik TG, 2000, HUM REPROD, V15, P999, DOI 10.1093/humrep/15.5.999
hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFAPESP
hcfmusp.scopus.lastupdate2024-05-17
relation.isAuthorOfPublication8ceff58e-e048-497c-9b17-0fe099ac7631
relation.isAuthorOfPublicationa8b0af8f-cf8d-4dcf-b2a6-63604abc6b5c
relation.isAuthorOfPublication.latestForDiscovery8ceff58e-e048-497c-9b17-0fe099ac7631
Arquivos
Coleções
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/42