Effect Of Gestrinone Research Articles

Antiestrogenic Effect of Gestrinone as an Inhibitor of [3H]-Estradiol Binding to Nuclear Type II Sites

Gestrinone has a biophysical antiestrogenic effect. But the mechanism of its antiestrogenic effect is not clear. Gestrinone blocked the increase of estrogen binding of nuclear type II sites and uterine weight in the estrogen-treated immature rabbit. Competitive assays indicated that gestrinone, at low concentrations (0.4 approximately 4 nM), inhibited [3H]-estradiol binding to nuclear type II sites. This inhibitory effect was the same as the addition of 20 microM diethyl-stilbestrol. This inhibition with gestrinone on [3H]-estradiol binding to nuclear type II sites appeared only when used at concentrations less than an equivalent molar of [3H]-estradiol. Time course analysis of the gestrinone binding inhibition showed that within the first 6 min gestrinone did not inhibit specific [3H]-estradiol binding to nuclear type II sites. This gestrinone-mediated inhibition was not observed in soluble fractions such as the cytosolic and KCl-extracted nuclear binding sites. These results suggest that gestrinone acts primarily on the nuclear fraction and then it operates the inhibitory mechanism on estradiol binding to nuclear type II sites.

Effect of gestrinone in endometriosis tissue and endometrium.

The effects of gestrinone (R 2323) on endometrial and endometriosis tissue concentrations of cytosol estrogen and progestin receptors and the activity of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were investigated in 11 patients operated on because of suspected external endometriosis. Serum concentrations of luteinizing hormone, follicle-stimulating hormone, estradiol (E2), progesterone, testosterone (T), and sex-hormone-binding globulin (SHBG) were also investigated. After one control cycle, the patients received 2.5 mg of oral gestrinone twice weekly from the fifth day of the first treatment cycle until the eighth day of the second treatment cycle, the day of operation being day 10. Treatment with gestrinone decreased serum concentrations of T during the second treatment cycle and effected a major decrease in SHBG during both treatment cycles, resulting in highly increased free T and free E2 indices. The effects of gestrinone on the endometrium, a decrease in estrogen and progestin receptors, and induction of 17 beta-HSD are characteristic progestin actions. These parameters remained unchanged in endometriosis tissue. Our data indicate that gestrinone has effects that are typical of androgens and progestins in patients with endometriosis.

性腺細胞, 子宮内膜細胞に及ぼすProgestin製剤（Gestrinone）の影響

Gestrinone (R 2323) is a synthetic progestogen, and noteworthy agent for endometriosis treatment. The effect of this reagent on cultured cells from porcine granulosa, human endometrial and endometrial carcinoma origin was investigated concerning their hormonal activities and cell proliferations. Also, the effect of gestrinone on the serum levels of gonadotropins and gonadal steroids in patients with XY gonadal dysgenesis (Swyer's syndrome) and uterine myoma was studied. The monolayer cell colony established from the endometrial tissue fragments was positively stained by PAS similar to the secretory phase endometrium by 10 ng/ml gestrinone in the culture media. Endometrial carcinoma cells from a 65-year-old patient were proliferated by gestrinone at the concentration of 50 ng/ml in the culture media. The effect of gestrinone on the secretions of progesterone and estradiol-17 beta with or without hCG/testosterone from the cultured porcine granulosa cells was also investigated. Progesterone secretions were stimulated at the 50 ng/ml concentration of gestrinone, especially in association with hCG. Nonetheless, at the concentration of 500 ng/ml, those were inhibited. The secretions of estradiol-17 beta were stimulated by this reagent both with and without testosterone in dose-dependent manners. The effect of 25 mg gestrinone administration for 3 days on the levels of LH, FSH, progesterone and estradiol-17 beta in a patient with XY gonadal dysgenesis was as follows. Both LH and FSH levels gradually decreased, whereas estradiol-17 beta level was increased. The same dosage of this reagent was administered to a patient with uterine myoma on her menstrual days 7, 8, and 9.(ABSTRACT TRUNCATED AT 250 WORDS)