Pasqualini J R, Paris J, Sitruk-Ware R, Chetrite G, Botella J
Hormones and Cancer Research Unit, Institut de Puériculture, Paris, France.
J Steroid Biochem Mol Biol. 1998 Apr;65(1-6):225-35. doi: 10.1016/s0960-0760(98)00028-4.
In the last years there has been an extraordinary development in the synthesis of new progestins. These compounds are classified, in agreement with their structure, in various groups which include progesterone, retroprogesterones, 17alpha-hydroxyprogesterones, 19-norprogesterones, 17alpha-hydroxyprogesterone derivatives, androstane and estrane derivatives. The action of progestins is a function of many factors: its structure, affinity to the progesterone receptor or to other steroid receptors, the target tissue considered, the biological response, the experimental conditions, dose, and metabolic transformation. The information on the action of progestins in breast cancer patients is very limited. Positive response with the progestins: medroxyprogesterone acetate and megestrol acetate was obtained in post-menopausal patients with advanced breast cancer. However, extensive information on the effect of progestins was obtained in in vitro studies using hormone-dependent and hormone-independent human mammary cancer cell lines. It was demonstrated that in the hormone-dependent breast cancer cells, various progestins (nomegestrol acetate, tibolone, medrogestone, promegestone) are potent sulfatase inhibitory agents. The progestins can also involve the inhibition of mRNA of this enzyme. In another series of studies it was also demonstrated that various progestins are very active in inhibiting the 17beta-hydroxysteroid dehydrogenase for the conversion of estrone to estradiol. More recently it was observed that the progestins promegestone or medrogestone stimulate the sulfotransferase for the formation of estrogen sulfates. Consequently, the blockage in the formation of estradiol via sulfatase, or the stimulatory effect on sulfotransferase activity, by progestins can open interesting and new possibilities in clinical applications in breast cancer.
在过去几年中，新型孕激素的合成取得了非凡进展。根据其结构，这些化合物被分为不同类别，包括孕酮、反孕酮、17α-羟基孕酮、19-去甲孕酮、17α-羟基孕酮衍生物、雄甾烷和雌甾烷衍生物。孕激素的作用取决于许多因素：其结构、对孕酮受体或其他甾体受体的亲和力、所考虑的靶组织、生物学反应、实验条件、剂量以及代谢转化。关于孕激素在乳腺癌患者中作用的信息非常有限。醋酸甲羟孕酮和醋酸甲地孕酮等孕激素在绝经后晚期乳腺癌患者中取得了阳性反应。然而，关于孕激素作用的广泛信息是在使用激素依赖性和激素非依赖性人乳腺癌细胞系的体外研究中获得的。结果表明，在激素依赖性乳腺癌细胞中，各种孕激素（醋酸诺美孕酮、替勃龙、美屈孕酮、普美孕酮）都是有效的硫酸酯酶抑制剂。孕激素还可抑制该酶的mRNA。在另一系列研究中还表明，各种孕激素在抑制17β-羟类固醇脱氢酶将雌酮转化为雌二醇方面非常活跃。最近观察到，孕激素普美孕酮或美屈孕酮可刺激硫酸转移酶形成雌激素硫酸盐。因此，孕激素通过抑制硫酸酯酶形成雌二醇或对硫酸转移酶活性的刺激作用，可能为乳腺癌的临床应用开辟有趣的新途径。
