Hypothalamic Insulin-Like Growth Factor-I Receptors Are Necessary for Hormone-Dependent Luteinizing Hormone Surges: Implications for Female Reproductive Aging

摘要

The following abstracts from Endocrinology have been selected by the editors of JCEM as being particularly relevant to readers interested in translational science. Epithelial ovarian cancer is thought to be derived from the ovarian surface epithelium (OSE) but often goes undetected in the early stages, and as a result, the factors that contribute to its initiation and progression remain poorly understood. Epidemiological studies have suggested that the female steroid hormones are involved in ovarian carcinogenesis and that women who use hormone replacement therapy are at increased risk of developing the disease. A novel transgenic mouse model of ovarian cancer (tgCAG-LS-TAg) was developed to examine the role of the female reproductive steroid hormones [176-estradiol (E,) and progesterone (P,)] on the initiation, progression, and pathology of ovarian cancer. The mouse model uses the Cre-LoxP system to induce expression of the simian virus 40 large and small T antigens (SV40TAg). After targeted induction of the oncogene in the OSE, mice develop poorly differentiated ovarian tumors and tumor dissemination to tissues within the abdominal cavity, and a subset develops hemorrhagic ascites. Treatment with P, had no impact on the disease, but E, altered the pathophysiology, resulting in an earlier onset of tumors, decreased overall survival time, and a distinctive papillary histology. Normal ovaries collected from mice treated with E,, but lacking expression of SV40 TAg, displayed an increase in the areas of columnar and hyperplastic OSE cells compared with placebo-treated controls. A better understanding of the mechanisms by which E; alters the morphology of normal OSE cells and reduces.