Whereas androgens are necessary for normal follicular growth and differentiation; androgen excess (like that seen in polycystic ovarian disease, PCOD) has been associated with hirsutism, menstrual irregularities, ovulatory dysfunction and infertility. We postulate that the clinical characteristics of women with PCOD may depend upon the developmental state when the androgen insult occurred and the duration of the insult. Two androgen-induced anovulation rat models are of interest since they produce functional and morphologic states in the ovary that are similar to the spectrum of those found in PCOD. The DHA-treated immature rat induces precocious puberty followed by PCOD and renders the animal in a state of constant diestrus. The DHA-treated mature rat produces PCOD and leads to constant vaginal estrus. Utilizing these models we will determine if there are any differences between the events leading to cystic formation or ovarian dysfunction when androgens are elevated near the time of puberty (as seen in some women with PCOD) versus androgens that are elevated in adulthood. In order to address these possibilities we will isolate cysts from PCOD induced ovaries by manual dissection. The remaining ovary will be exposed to collagenase to liberate follicles and interstitium. The follicles will be further processes to harvest granulosa cells and theca cells. Utilizing the follicle/cell isolation technique the following three Aims will be addressed: (1) to characterize the steroids produced by granulosa cells, thecal cells, cysts, follicles and stroma of ovaries from normal rats and 2 distinct rat models of androgen induced ovulatory failure; (2) to determine whether there are androgen-induced alterations in the levels of or functional activity of macromolecules involved in cholesterol synthesis, lipoprotein metabolism and steroid synthesis in experimentally induced PCOD and follicular atresia; (3) to evaluate the effects of PCOD on ovarian responsiveness to growth factors (TGF-beta, TNF-alpha, EGF, IGF-I, IGF-II). Results from such studies could provide for methods of treatment of PCOD that could be tested in PCOD patients.
| Parker Jr, C R; Conway-Myers, B A (1998) The effects of dehydroepiandrosterone (DHEA) on the thymus, spleen, and adrenals of prepubertal and adult female rats. Endocr Res 24:113-26 |
