A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor.
نویسندگان
چکیده
A single natural loss of function mutation of the follicle stimulating hormone receptor (FSHR) has been described to date. Present in the Finnish population it markedly impairs receptor function, blocking follicle development at the primary stage and presenting as primary amenorrhea with atrophic ovaries. When Western European women with this phenotype were examined for FSHR mutations the result was negative, suggesting that other etiologies corresponding to this clinical pattern are markedly more frequent. We now describe a novel phenotype related to mutations provoking a partial loss of function of the FSHR. A woman with secondary amenorrhea had very high plasma gonadotropin concentrations (especially FSH), contrasting with normal sized ovaries and antral follicles up to 5 mm at ultrasonography. Histological and immunohistochemical examination of the ovaries showed normal follicular development up to the small antral stage and a disruption at further stages. The patient was found to carry compound heterozygotic mutations of the FSHR gene: Ile160Thr and Arg573Cys substitutions located, respectively, in the extracellular domain and in the third intracellular loop of the receptor. The mutated receptors, when expressed in COS-7 cells, showed partial functional impairment, consistent with the clinical and histological observations: the first mutation impaired cell surface expression and the second altered signal transduction of the receptor. This observation suggests that a limited FSH effect is sufficient to promote follicular growth up to the small antral stage. Further development necessitates strong FSH stimulation. The contrast between very high FSH levels and normal sized ovaries with antral follicles may thus be characteristic of such patients.
منابع مشابه
P-206: Genetic Variations of FSH Receptor Gene in Patients with Premature Ovarian Failure and Diminished Ovarian Reserve Referred to Royan Institute
Background: Immaturity of the ovarian follicles results in an infertility citation called Premature Ovarian Failure (POF), affecting approximately 1% of women under the age of 40. Women with this disorder go through early menopause and have high levels of gonadotropin hormones (FSH & LH). Diminished Ovarian Reserve (DOR) is another infertility disorder in which women’s ovaries have the ability ...
متن کاملMutations of follicle-stimulating hormone and its receptor: effects on gonadal function.
The physiological functions of the two gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are quite well known in both males and females. Nevertheless, the recent unraveling of structures of the gonadotropin and gonadotropin receptor genes has provided us with tools to obtain completely new information on the functions of these hormones at the molecular level. Sever...
متن کاملCan fasting in the holy month of Ramadan affect on the levels of luteinizing hormone, follicle-stimulating hormone, and prolactin?
Adherence to the recommendations and obligations of Islam is of great importance in achieving a desirable lifestyle. Fasting in the holy month of Ramadan is one of the main principles of Islam, in which Muslims refrain from eating, drinking, oral medications, and smoking from Fajr (pre-dawn) to Maghrib (sunset). Islamic rules dictate that fasting is unacceptable if it causes harm to the health ...
متن کاملP-228: Altered Expression of Folliclestimulating Hormone Receptor and Luteinizing Hormone Receptor in Granulosa Cells from Women with Polycystic Ovary Syndrome
Background: Polycystic ovary syndrome (PCOS) is a common complex genetic endocrinopathy, affecting 5 - 10% of women at reproductive age. PCO granulosa cells seem to have abnormal responses to follicle- stimulating hormone (FSH). FSH is considered to be a pituitary glycoprotein that plays an important role during folliculogenesis as it promotes the proliferation and differentiation of granulosa ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of clinical investigation
دوره 102 7 شماره
صفحات -
تاریخ انتشار 1998