![]() ![]() The literature is replete with reports that administration of diethylstilbestrol often leads to an hypertrophy of the adrenal cortex (Noble, 1938 Mellish et al., 1940 Von Hamm et al., 1941). There exist marked strain differences in the occurrence of hypophyseal chromophobe adenomata following estrogenic stimulation (Gardner and Strong, 1940 Gardner, 1941). The situation in the mouse is somewhat different. Unfortunately, most of the workers employed nonpedigreed rats or failed to specify the strain of rats used. THE EFFECT OF STRAIN, ESTROGEN, AND DOSAGE ON THE REACTION OF THE RAT'S PITUITARY AND ADRENAL TO ESTROGENIC STIMULATION THE EFFECT OF STRAIN, ESTROGEN, AND DOSAGE ON THE REACTION OF THE RAT'S PITUITARY AND ADRENAL TO.Ībstract There have been many reports that prolonged treatment of rats with estrogenic hormones frequently leads to the production of chromophobe adenomata of the pituitary (Zondek, 1936 Wolfe and Wright, 1938 Nelson, 1943 Selye, 1944). In combined oral contraceptive pills (COCP) with ethinyloestradiol, dienogest conjuction therapy effectively reduces the symptoms of acne and hirsutism, as well as improving excessively heavy or prolonged menstrual bleeding. It has no glucocorticoid or mineralocorticoid effects. Visanne displays no antiestrogenic activity as it activate neither estrogen receptor (ER) α nor ERβ, and causes hypoestrogenic effects instead as it is shown to decrease the relative expressions of ERβ and ERα. In clinical trials composing of patients with endometriosis, dienogest therapy effectively reduced painful symptoms and endometriotic lesions associated with the disorder. 1mg/kg of dienogest also directly inhibits ovulation. A dose of 2 mg inhibits the growth of ovarian follicles at 10 mm and maintains the concentration of progesterone at a low level, but has a weak inhibitory effect on FSH and LH. It also mediates an antiandrogenic effect that is equivalent to approximately one third that of cyproterone acetate. Visanne exhibits a very potent progestagenic effect in the endometrium, and causes endometrial atrophy after prolonged use. Additional properties eg, immunologic and antiangiogenic effects, seem to contribute to the inhibitory action of dienogest on cell proliferation. When given continuously, dienogest leads to a hypoestrogenic, hypergestagenic endocrine environment causing initial decidualization of endometrial tissue followed by atrophy of endometriotic lesions. Visanne acts on endometriosis by reducing the endogenous production of estradiol and thereby suppressing the trophic effects of estradiol on both the eutopic and ectopic endometrium. ![]() Visanne has no significant androgenic, mineralocorticoid or glucocorticoid activity in vivo. Despite its low affinity to the progesterone receptor, dienogest has a strong progestogenic effect in vivo. Visanne binds to the progesterone receptor of the human uterus with only 10% of the relative affinity of progesterone. ![]() Visanne is a nortestosterone derivative with no androgenic but rather an antiandrogenic activity of approximately 1/3 of that of cyproterone acetate. ![]()
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