{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T17:46:08Z","timestamp":1765993568378},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2008,10,9]],"date-time":"2008-10-09T00:00:00Z","timestamp":1223510400000},"content-version":"vor","delay-in-days":2883,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2000,11,17]]},"abstract":"<jats:sec><jats:title>OBJECTIVE<\/jats:title><jats:p>Familial or sporadic male\u2010limited precocious puberty is a distinct and unusual gonadotrophin\u2010independent form of sexual precocity caused by constitutively activating mutations of the luteinizing hormone receptor (LHR). In the present study, we evaluated the effect of known activating mutations at different sites of the LHR gene on the pituitary\u2013gonadal axis in both sexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS<\/jats:title><jats:p>Four unrelated Brazilian boys (I\u2010IV) with gonadotrophin\u2010independent precocious puberty and two asymptomatic females (V\u2010VI), a sister and mother of two of the affected boys, were studied. Patients I, II and V carried the Ala568Val mutation located at the third intracellular loop of the LHR. Patient III carried the Leu457Arg mutation at the third transmembrane helix, and patients IV and VI carried the Thr577Ile mutation at the sixth transmembrane helix of the LHR.<\/jats:p><\/jats:sec><jats:sec><jats:title>MEASUREMENTS<\/jats:title><jats:p>Serum levels of LH, FSH, testosterone, and oestradiol under basal and GnRH\u2010stimulated conditions were determined in all patients. Testosterone levels were also measured after a hCG stimulation test in patient III.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Basal LH and FSH levels were prepubertal in all boys studied. The GnRH\u2010stimulated serum LH and FSH levels were prepubertal in three boys (I, II and IV), whereas patient III showed totally suppressed LH and FSH levels at ages 2 and 7 years (bone ages 6 and 14 years, respectively). Serum testosterone levels ranged from 3.8 to 69.5\u2003nmol\/l in the four boys. Patient III had the highest testosterone levels that did not respond to hCG stimulation. The 4 year\u2010old girl (patient V) was phenotypically normal and the acute response to GnRH was indicative of prepubertal status. Patient VI had normal menstrual cycles and fertility.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>These findings indicate variable effects of LHR activating mutations on the pituitary\u2013gonadal axis in boys that can result in lack of normal LH and FSH release. In contrast, prepubertal and adult females were asymptomatic and had normal basal and GnRH\u2010stimulated LH and FSH levels.<\/jats:p><\/jats:sec>","DOI":"10.1046\/j.1365-2265.2000.01135.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T10:47:02Z","timestamp":1047379622000},"page":"609-613","source":"Crossref","is-referenced-by-count":31,"title":["The effect of distinct activating mutations of the luteinizing hormone receptor gene on the pituitary\u2013gonadal axis in both sexes"],"prefix":"10.1111","volume":"53","author":[{"given":"Ana Claudia","family":"Latronico","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa Selma S.","family":"Lins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vinicius Nahime","family":"Brito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivo Jorge P.","family":"Arnhold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berenice B.","family":"Mendonca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,10,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.84.10.3539"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1995.tb02692.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(85)80460-1"},{"key":"e_1_2_6_5_1","unstructured":"Greulich W.W.&Pyle S.I.(1985)Radiographic Skeletal Development of the Hand and Wrist. 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