アンドロジェン性不妊ラットの多嚢胞性卵巣におけるステロイド代謝の研究

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Cystic ovaries have long been recognized as a common case of infertility in domestic animals, and the relevant works have been reported from many laboratories. However, very little is known about the etiology of ovarian cysts. Administration of testosterone propionate to neonatal female rats results infertility characterized by polycystic ovaries. An abnormal pattern of steroidogenesis by the polycystic ovaries of such androgen-sterilized rats has been already reported. In previous reports from this labolatory the six preg-nane compounds (progesterone , 5α-pregnane-3, 20-dione, 3α-hydroxy-5α-pregnan-20-one, 20α-hydroxy-4-pregnen-3-one, 20α-hydroxy-5α-pregnan-3-one and 5α-pregnane-3α, 20α-diol) have been identified in the ovarian venous plasma of LH-stimulated rats and LH appeared to evoke a remarkable increase of secretion of progesterone, 5α-pregnane-3,20-dione, and 3α-hydroxy-5α-pregnan-20-one from the rat ovary. In the present investigation, I studied the differences between polycystic ovaries of androgen-sterilized rats and the ovaries of normal cycling rats with regard to secretion of estrogens (estrone, 17β-estradiol and estriol) and pregnane compounds. Before I undertook these experiments I studied the method for simulataneous determination of the above steroids in the rat plasma. The pregnane compounds were assayed by gas-liquid chromatography, while the estrogens were determined by the radioimmuno-assay technique. The accuracy and precison of the assay method for the each steroids were satisfactory. A comparison of steroid levels in the ovarian venous effluent of rat with and without destruction of selected tissue components by x-irradiation of the ovaries suggests that the interstitial gland tissue has potency to secret progesterone and 3α-hydroxy-5α-pregnan-20-one, the follicles contribute to the secretion of progesterone, 5α-pregnane-3,20-dione and 3α-hydroxy-5α-pregnan-20-one, and the corpora lutea contribute to the secretion of progesterone , 20α-hydroxy-4-pregnen-3-one and 5α-pregnane-3α, 20α-diol. Concentration of 5α-pregnane-3, 20-dione and 3α-hydroxy-5α-pregnan-20-one in the ovarian venous plasma during the estrous cycle in the rat increased concurently during LH surge of late proestrus. The secretion of these two progesterone metabolites was also considerably increased in response to LH (2μg) in immature rats treated with PMS. However, the response of these steroids in the polycystie ovaries of androgen-sterilized rats remained at low levels, suggesting low 5α-reductase activity in the cystic ovary. Becoause it is known that follicular tissue is involved in the production of estrogens, I studied the interrelationship between the secretion of the 5α and 3α, 5α-reduced metabolites of progesterone and estrogens in follicular polycystic ovaries of androgen-sterilized rats. Normal ovaries of diestrus-2 rats were used as controls for the polycystic ovaries. At this stage, normal ovaries secrete comparable amounts of estrogens as the polycystic ovaries. An injection of LH significantly increased the secretion of 5α-pregnane-3, 20-dione and 3α-hydroxy-5α-pregnan-20-one within 1 h in normal ovaries, but the response of polycystic ovaries was low. The polycystic ovaries exhibited a marked increase in the secretion of estrogens in response to LH, whereas normal ovaries showed no significant change. These results suggest the presence of a metabolic interrelationship between 5α-reductase activity and estrogen secretion in polycystic ovaries of androgen-sterilized rats. At present, details of the metabolic interrelationships are obscure. But 5α-reductase will convert estrogen precursors to 5α-reduced metabolites. Furthermore, 5α-pregnane-3 , 20-dione is known to be an effective inhibitor of the 17α-hydroxysteroid C-17, 20-lyase in vitro. Thus, the low 5α-reductase activity in polycystic ovaries may contribute to estrogen production by saving estrogen precursors and by maintaining the concentration of 5α-pregnane-3, 20-dione, and inhibitor of estrogen formation, at a low level.
大阪府立大学の論文
1980-03-31

アンドロジェン性不妊ラットの多嚢胞性卵巣におけるステロイド代謝の研究

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