{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:10:11Z","timestamp":1791177011175,"version":"4.1.0"},"reference-count":72,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,1]]},"abstract":"<jats:p>The LH receptor (LHR) is critical for steroidogenesis and gametogenesis. Its essential role is underscored by the developmental and reproductive abnormalities that occur due to genetic mutations identified in the human LHR. In males, activating mutations are associated with precocious puberty and Leydig cell hyperplasia. To generate a mouse model for the human disease, we have introduced an aspartic acid to glycine mutation in amino acid residue 582 (D582G) of the mouse LHR gene corresponding to the most common D578G mutation found in boys with familial male-limited precocious puberty (FMPP). In transfected cells, mouse D582G mLHR exhibited constitutive activity with a 23-fold increase in basal cAMP levels compared with the wild-type receptor. A temporal study of male mice from 7 days to 24 weeks indicated that the knock-in mice with the mutated receptor (KiLHRD582G) exhibited precocious puberty with elevated testosterone levels as early as 7 days of age and through adulthood. Leydig cell-specific genes encoding LHR and several steroidogenic enzymes were up-regulated in KiLHRD582G testis. Leydig cell hyperplasia was detected at all ages, whereas Sertoli and germ cell development appeared normal. A novel finding from our studies, not previously reported in the FMPP cases, is that extensive hyperplasia is commonly found around the periphery of the testis. We further demonstrate that the hyperplasia is due to premature proliferation and precocious differentiation of adult Leydig cells in the KiLHRD582G testis. The KiLHRD582G mice provide a mouse model for FMPP, and we suggest that it is a useful model for studying pathologies associated with altered LHR signaling.<\/jats:p>","DOI":"10.1210\/en.2012-2179","type":"journal-article","created":{"date-parts":[[2013,7,17]],"date-time":"2013-07-17T02:16:38Z","timestamp":1374027398000},"page":"3900-3913","source":"Crossref","is-referenced-by-count":53,"title":["Precocious Puberty and Leydig Cell Hyperplasia in Male Mice With a Gain of Function Mutation in the LH Receptor Gene"],"prefix":"10.1210","volume":"154","author":[{"given":"Stacey R.","family":"McGee","sequence":"first","affiliation":[{"name":"Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois 62901"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prema","family":"Narayan","sequence":"first","affiliation":[{"name":"Department of Physiology, Southern Illinois University School of Medicine, Carbondale, Illinois 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