Chambon Y
Laboratoire d'Histologie et d'Embryologie, Faculté de médecine de Rennes.
Bull Acad Natl Med. 1993 Feb;177(2):177-86.
Our purpose is to provide a review of studies performed since forty five years, concerning interactions of natural or synthetic estrogens and progestins. In this paper, the terms synergism and antagonism have to be considered in a broader sense than usually done. In addition to the classical concepts of succession and of simultaneity synergism between estradiol and progesterone, notions of "saving" and of "necessity" synergism came from decidualization studies in the rabbit (1949). The necessity synergism put definitively and end to the idea that estradiol was only a female hormone and progesterone a mother one. Our research in the field of ovum implantation showed also that estrogens might be secreted by mammalian ova (1949), which is now well established. The participation of estrogens to the process of decidualization in the rat suggested even (1958, 1959) their role in the starting implantation. From 1960, synthetic estrogens and progestins were tested, in a first step especially ethynylestradiol and chlormadinone acetate. In the rabbit and in the rat, these new tools permitted us to dissociate the hormonal needs of embryonic growth and of morphogenesis (1965). The studies related to the effects of these analogs upon the adrenal gland, as upon the hypophysis (1963), led to their clinical use in the treatment of advanced breast cancers, and the studies concerning their effects in the ovulation to the discovery of the antiovulatory synergism of synthetic estrogens and progestins (1966, 1982). These observations are in agreement with the Courrier rules with regard to the relationships between the relative, but also absolute, quantities of estradiol and of progesterone administered, and the obtained biological effects. Nevertheless, progestins exist with incomplete or, on the contrary, superfluous pharmacological activities. In the extreme, the estrogenic properties of norethisterone take precedence over its progestogenic properties when administered doses are growing (1977). These phenomena have now to be understood at a molecular level. Though explanations are presently available for some processes, many of them remain to day unexplained, and inversely other explanations are coming into sight.
我们的目的是对45年来有关天然或合成雌激素与孕激素相互作用的研究进行综述。在本文中，协同作用和拮抗作用这两个术语的含义要比通常理解的更宽泛。除了雌二醇和孕酮之间经典的相继性和同时性协同作用概念外，“节省”和“必要性”协同作用的概念源于对兔子蜕膜化的研究（1949年）。必要性协同作用最终彻底否定了雌二醇只是一种雌性激素而孕酮只是一种母体激素的观点。我们在卵子着床领域的研究还表明，哺乳动物的卵子可能分泌雌激素（1949年），这一点现在已得到充分证实。雌激素参与大鼠蜕膜化过程的研究甚至表明（1958年、1959年）它们在启动着床过程中的作用。从1960年起，开始对合成雌激素和孕激素进行测试，第一步主要测试乙炔雌二醇和醋酸氯地孕酮。在兔子和大鼠身上，这些新工具使我们能够区分胚胎生长和形态发生的激素需求（1965年）。关于这些类似物对肾上腺以及垂体影响的研究（1963年），促使它们在晚期乳腺癌治疗中得到临床应用，而关于它们对排卵影响的研究则促成了合成雌激素和孕激素抗排卵协同作用的发现（1966年、1982年）。这些观察结果与库里尔规则中关于所给予的雌二醇和孕酮的相对量以及绝对量与所获得的生物学效应之间关系的描述相符。然而，孕激素存在药理学活性不完全或相反地过度的情况。极端情况下，当炔诺酮的给药剂量增加时，其雌激素特性会优先于其孕激素特性（1977年）。现在必须从分子层面理解这些现象。尽管目前对一些过程已有解释，但其中许多至今仍无法解释，反之，其他一些解释也开始浮现。
