Réceptologie work showed that the acetate nomégestrol a high specificity and affinity for the progesterone receptor, especially in the normal human breast tissue and cancer. It significantly inhibits the synthesis of progesterone receptors in breast cancer cells, hormone-dependent human T-47D in a culture in estrogen, which reflects its strong activity progestogen. However, it has no affinity for the estrogen receptor and is devoid of any estrogenic potential, as confirmed by the absence of induction of alkaline phosphatase activity in Ishikawa cells. The nomégestrol acetate inhibits the synthesis of estrogen receptors in estrogen-induced, mechanism of action of its anti-estrogenic activity intrinsic marked. Finally, it is devoid of any androgenic activity, in contrast to androgenic progestins (derived from 19-nortestosterone, medroxyprogesterone acetate) may have an indirect impact on the breast by the changes in the synthesis of SHBG (sex hormone binding globulin) and the IGF-I (insulin-like growth factor-I) induced. In work on the effects of progestogens on the enzyme activities involved in the biosynthesis of intramammary estradiol (E2), the nomégestrol acetate in vitro is able to control the levels of E2 in cancerous breast tissue: it blocks the formation of 'E2 in human breast cancer cells MCF-7 and T-47D by inhibiting the activity of the sulfatase that allows the conversion of estrone sulfate (E1S) into estrone (E1) and the 17?-hydroxysteroid dehydrogenase type 1, which catalyzes the conversion of E1 into E2. In addition, it stimulates the activity of the sulfotransferase and therefore the transformation of non-conjugated estrogens E1 and E2 in estrogen sulfates, biologically inactive. Work in vitro on cell proliferation have highlighted the one hand, the absence of stimulation by acetate nomégestrol the proliferation of MCF-7 cells cultured in a medium devoid of estrogens and on the other hand, a nomégestrol antiproliferative effect of acetate on T-47D cells in estrogen.
[...] Nomégestrol effects of acetate on cell proliferation and apoptosis in breast Mammary cell proliferation: As already noted, the estrogenic potential of a product is an important consideration because of the risk represented by the carcinogenic estrogen stimulation induces cell proliferation. Work in vitro showed that progestins derived from 19-nortestosterone (such as noréthynodrel, norethindrone, norgestrel, gestodene), because of their intrinsic estrogenic properties stimulate proliferation of human breast cancer cells, hormone-dependent positive for receptor estrogen (ER MCF- 7 and T47-D: A18, set in a culture medium deprived of estrogens. [...]
[...] The lack of induction by acetate nomégestrol alkaline phosphatase activity which is a specific response to estrogen stimulation via the estrogen receptor, confirms the absence of any estrogenic activity of this progestin derived from 19-norprogestérone. In contrast, the intrinsic estrogen progestin derived from 19- nortestosterone is expressed in vivo after metabolic reductions: it is mediated via the estrogen receptor through their reduced metabolites. Regulation of estrogen receptor: Unlike progestins derived from 19- nortestosterone which induce the synthesis of estrogen receptors as well as that of progesterone receptors in relation to their estrogenic action, the nomégestrol acetate inhibits the synthesis of estrogen receptors in relation to its high activity progestomimétique, principal mechanism of action by which it exerts its anti-estrogenic activity intrinsic. [...]
[...] Treatment with nomégestrol acetate causes a significant decrease in spontaneous mastodynies, the feeling of breast swelling and pain on palpation of the breasts 0.001 with a significant intergroup difference: namely, after 4 months of treatment, mastodynies Unsolicited are absent or slight in 85% of women in nomégestrol acetate 53% against placebo 0.05 Improved opacities visualized breast mammography at 4 months is also significant in nomégestrol acetate compared to placebo 0.05 the global assessment by the investigator of the evolution of anomalies radiological identified based on comparisons of photographs in connection with the initial state, taking into account the density of breast tissue, the appearance of homogeneous or heterogeneous and its nodularity. [...]
[...] In addition, through its androgenic activity, such as certain progestins derived from 19-nortestosterone or medroxyprogesterone acetate administered orally, induced by first-pass effect of hepatic changes in the synthesis of SHBG (sex hormone binding globulin) and IGF-I (insulin-like growth factor-I) with a potential indirect impact on the breast, especially when their association with oral estrogen through hormone replacement therapy (HRT) for menopause. At present, it is increasingly important to differentiate progestins whose pharmacological properties and subsequent biological effects, particularly breast, probably vary according to their molecular structure even. [...]
[...] The cellular mechanism of the antiandrogenic action of nomegestrol acetate, a new 19-nor-progestagen, on the rat prostate. Endocrinologic Acta 1987, 115: 544-50. Sasano Harada N. Intratumoral aromatase in human breast, endometrial, and ovarian malignancies. Endocr Rev 1998; 19: 593-607. Suzuki Moriya Ishida Kimura OHUCHI Sasano H. In situ production of estrogens in human breast carcinoma. Breast Cancer 2002; 296-302. Clemons Goss P. Estrogen and the risk of breast cancer. N Engl J Med 2001; 344: 276-85. Pasqualini JR, Chetrite Blacker Feinstein MC, Delalonde Talbi M et al. [...]
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