کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2028642 1070432 2009 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterization of the ovarian and reproductive abnormalities in prepubertal and adult estrogen non-responsive estrogen receptor α knock-in (ENERKI) mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Characterization of the ovarian and reproductive abnormalities in prepubertal and adult estrogen non-responsive estrogen receptor α knock-in (ENERKI) mice
چکیده انگلیسی

Estrogen non-responsive estrogen receptor alpha (ERα) knock-in (ENERKI) mice have a mutation (glycine 525 to leucine, G525L) in the ligand-binding domain of ERα. The mutant ERα protein has a significantly lower affinity and response to endogenous estrogens, while not altering growth factor activated ligand-independent pathways. ENERKI females demonstrated signs of early follicle development as determined by a significant increase in antral follicle formation by 20 days of age. Adult ENERKI females were infertile, had hemorrhagic ovarian follicular cysts, and failed to develop corpora lutea in response to a superovulation regimen. These results illustrate the importance of ERα ligand-induced signaling for ovarian development and for estrogen feedback on the hypothalamus and pituitary.Although ERα ligand-induced signaling by endogenous estrogens is lost in ENERKI females, the ERα selective agonist propyl pyrazole triol (PPT), a synthetic nonsteroidal compound, is still able to activate G525L ERα in vivo to increase uterine weight. To test whether PPT could restore ligand-dependent receptor activation, ENERKI females were treated with PPT and evaluated for spontaneous ovulation, ovarian hemorrhagic cysts, and LH serum levels. Daily PPT treatments beginning on day 4 of life prevented formation of ovarian hemorrhagic cysts in adult ENERKI animals. In accordance with this result, preputial gland weight and LH levels were also lowered in these animals, indicating PPT treatments most likely led to restoration of ERα negative feedback of the hypothalamic–pituitary axis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Steroids - Volume 74, Issue 12, 4 November 2009, Pages 913–919
نویسندگان
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