Submission Number: DAN-4-16-6

Abstract Number: 496

APPEARANCE OF PHENOTYPIC CHANGES IS ASSOCIATED WITH ESTROGEN DEFICIENCY IN THE FOLLICLE-STIMULATING RECEPTOR KNOCK OUT (FORKO) FEMALE MOUSE.

N Danilovich, P Suresh Babu, W Xing, M Gerdes, H Krishnamurthy and MR Sairam*

Molecular Reproduction Research Laboratory, Clinical Research Institute, Montreal, Quebec, Canada. ¹

Abstract:
Follicle-stimulating hormone (FSH) is the primary hormone that regulates development and maturation of the ovarian follicles in mammals by interacting with its specific receptor expressed on granulosa cells. We have produced FSH receptor knock out (FORKO) mice to study the role of receptor signalling on the female reproductive system. Deleting the entire repertoire of FSH receptors induced major changes in fertility of null females as well as heterozygotes. The FORKO females exhibit acyclicity and are infertile. Lack of FSH receptor signalling causes severe underdevelopment of ovary and uterus leading to >95% decline in the estrogen production. Early loss of estrogen leads to obesity and skeletal abnormalities which are also some of the changes experienced by menopausal women. The expression of estrogen receptors a and b genes as well as proteins in target tissues of FORKO mice are intact. Loss of estrogen creates an imbalance in the A and B forms of progesterone receptor in the uterus. Aromatase gene transcription and translation are unaltered. These changes are reminiscent of the ovarian dysfunction and other major symptoms that occur in post-menopausal women. Thus, the phenotypes evident in these mutant provide an experimental model to explore the molecular mechanisms of menopause and developing preventive therapeutic strategies. Because, the heterozygous females exhibit initially reduced fertility and subsequently early reproductive senescence, represent an interesting animal model to explore the mechanisms of reproductive failure during mid-life in women (Supported by Medical Research Council of Canada).

Keywords: FSH receptor, Estrogen, Menopause, Osteoporosis

This abstract is being presented at: 8:00 AM in session:
Hormone Receptors