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D580H and D580Y mutations of mFSHR bind FSH, but the activity of the former is neither ligand-dependent nor promiscuous towards LH\/human choriogonadotropin stimulation. Transgenic expression of mFshrD580H in granulosa cells leads to abnormal ovarian structure and function in the form of hemorrhagic cysts, accelerated loss of small follicles, augmented granulosa cell proliferation, increased estradiol biosynthesis, and occasional luteinized unruptured follicles or teratomas. The most affected mFshrD580H females are infertile with disturbed estrous cycle and decreased gonadotropin and increased prolactin levels. Increased estradiol and prolactin apparently underlie the enhanced development of the mammary glands, adenomatous pituitary growth, and lipofuscin accumulation in the adrenal gland. The influence of the mFSHRD580Y mutation is milder, mainly causing hemorrhagic cysts in transgenic mFSHRD580Y and mFSHRD580Y -knock-in mice. The results demonstrate that gain-of-function mutations of the FSHR in mice bring about distinct and clear changes in ovarian function, informative in the search of similar mutations in humans.<\/jats:p>","DOI":"10.1210\/en.2009-0966","type":"journal-article","created":{"date-parts":[[2010,2,20]],"date-time":"2010-02-20T02:10:18Z","timestamp":1266631818000},"page":"1872-1883","source":"Crossref","is-referenced-by-count":45,"title":["Female Mice Expressing Constitutively Active Mutants of FSH Receptor Present with a Phenotype of Premature Follicle Depletion and Estrogen Excess"],"prefix":"10.1210","volume":"151","author":[{"given":"Hellevi","family":"Peltoketo","sequence":"first","affiliation":[{"name":"Institute of Reproductive and Developmental Biology (H.P., R.K., I.T.H.), Imperial College London, London W12 0NN, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leena","family":"Strauss","sequence":"first","affiliation":[{"name":"Department of Physiology (L.S., M.P., I.T.H.), Institute of Biomedicine, University of Turku, FIN-20520 Turku, Finland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riikka","family":"Karjalainen","sequence":"first","affiliation":[{"name":"Institute of Reproductive and Developmental Biology (H.P., R.K., I.T.H.), Imperial College London, London W12 0NN, United Kingdom;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meilin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Molecular Physiology and Biophysics (M.Z., D.L.S.), The Roy J. and Lucille A. 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