Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2010) 21 P326

SFEBES2009 Poster Presentations Reproduction (23 abstracts)

Female mice expressing constitutively active FSH receptor present with a phenotype of premature follicle depletion, premature aging and teratomas

Hellevi Peltoketo 1 , Leena Strauss 2 , Riikka Karjalainen 1 , Meilin Zhang 3 , Gordon Stamp 1 , Deborah Segaloff 3 , Matti Poutanen 2 & Ilpo Huhtaniemi 1,


1Imperial College London, London, UK; 2University of Turku, Turku, Finland; 3The University of Iowa, Iowa City, Iowa, USA.


Strong gain-of-function mutations have not been identified in humans in the FSH receptor (FSHR), while such mutations are common among many other G-protein-coupled receptors. In order to predict consequences of such mutations on humans, D580 (D6.44) mutant forms of mouse (m) FSHR were expressed under the human anti-Müllerian hormone promoter in transgenic mice. Transgenic expression of mFshrD580H in granulosa cells led 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. While the litters of the females with low transgene expression were larger than those of wild types, the most affected mFshrD580H females were infertile with disturbed estrus cycle, and decreased gonadotropin and increased prolactin production. Increased estradiol and prolactin apparently underlay the enhanced development of the mammary glands, adenomatous pituitary growth and lipofuscin accumulation in the adrenal gland, also detected in the transgenic females. The influence of the mFSHRD580Y mutation was milder, mainly causing hemorrhagic cysts. 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.

Article tools

My recent searches

No recent searches.