Previous histological and histochemical studies indicate that ovaries of postmenopausal women with endometrial carcinoma are steroidogenically more active than in menopausal women without this neoplasm. Recent endocrine studies confirm this observation. This increase in ovarian steroid secretion might play a role in the pathogenesis of endometrial cancer. The long term objective of the study will be to investigate this increased ovarian steroidogenesis in women with endometrial cancer and determine the factors that cause it. Increase in ovarian stromal steroidogenesis could be due to 1) the availability of increased quantities of bioactive LH 2) some other hormone, such as insulin (I) or insulin like growth factors (IGFs) might be stimulating the ovarian stroma. 3) Ovarian stroma of women with endometrial cancer may be steroidogenically more active and show more response to LH than that of women without cancer. The purpose of this present study will be to evaluate these hypotheses.
The specific aims of the project will be to carry out the following studies and compare results between postmenopausal patients with endometrial carcinoma and normal postmenopausal controls matched for age, years since menopause, and percentage of ideal body weight.
The first aim i s to investigate whether there is an increase in LH secretion with an increase in bioactive LH levels in postmenopausal women with endometrial carcinoma. Mean LH levels (calculated from multiple samples obtained over 6 hr period) and pulse frequency and pulse amplitude of LH secretion will be compared between patients and controls. Mean bioactive LH (bio-LH) levels and the ratio of bio-LH to immunoreactive-LH (bio-LH/i-LH) will be compared between the two groups.
The second aim i s to measure immunoreactive insulin levels, and insulin like growth factors (IGFI and IGFII) in both groups of women. Insulin receptor concentrations in circulating monocytes and ovarian stromal tissue will be measured to assess the degree and nature of insulin resistance in these women.
The third aim i s to evaluate in vitro, the steroid production in response to LH, I and insulin like growth factors of isolated ovarian stromal tissues of postmenopausal women with endometrial cancer. Production of testosterone (T), androstenedione (A), Progesterone (P), estrone (E1) and estradiol (E2) per milligram of ovarian stroma will be determined to see whether a statistically significant difference is found between the cancer patients and controls.
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