Pasqualini J R, Ebert C
Hormones and Cancer Research Unit, Paris, France.
Gynecol Endocrinol. 1999 Jun;13 Suppl 4:11-9. doi: 10.1080/gye.13.s4.11.19.
Developments in the synthesis of different progestins have opened up new possibilities for the biological effects and therapeutic uses of these compounds. The actions of progestins are a function of their 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. Data on the action of progestins in breast cancer patients are very limited. A positive response with the progestins medroxyprogesterone acetate and megestrol acetate has been obtained in postmenopausal 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 hormone-dependent breast cancer cells, various progestins (nomegestrol acetate, medrogestone, promegestone) as well as tibolone, are potent sulfatase-inhibitory agents. Progestins may also be involved in the inhibition of the mRNA of this enzyme. In another series of studies, it was also demonstrated that various progestins are very active in inhibiting the 17 beta-hydroxysteroid dehydrogenase for the conversion of estrone to estradiol. More recently, it has been observed that promegestone or medrogestone stimulates the sulfotransferase for the formation of estrogen sulfates. Clinical trials of these enzymatic effects on the formation and transformation of estradiol in breast cancer patients could be the next step to investigate new therapeutic possibilities for this disease.
不同孕激素合成方面的进展为这些化合物的生物学效应和治疗用途开辟了新的可能性。孕激素的作用取决于其结构、对孕激素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数据非常有限。在晚期绝经后乳腺癌患者中，醋酸甲羟孕酮和醋酸甲地孕酮这两种孕激素已获得阳性反应。然而，关于孕激素作用的广泛信息是在使用激素依赖性和非激素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、甲羟孕酮、普美孕酮）以及替勃龙都是有效的硫酸酯酶抑制剂。孕激素也可能参与对该酶mRNA的抑制。在另一系列研究中，还表明各种孕激素在抑制将雌酮转化为雌二醇的17β-羟类固醇脱氢酶方面非常活跃。最近，有人观察到普美孕酮或甲羟孕酮会刺激硫酸转移酶以形成雌激素硫酸盐。针对这些酶促作用对乳腺癌患者雌二醇形成和转化影响的临床试验可能是下一步研究该疾病新治疗可能性的方向。
