STUDIES ON THE INTERACTIONS OF OESTRIOL AND PROGESTERONE

Since oestriol was discovered in the urine of pregnant women over 30 years ago (Doisy, Mayer, Levinand & Curtis, 1930; Marrian, 1930), most workers have considered it simply as a metabolite of oestrone and oestradiol, an excretory product of no further physiological significance. More recently, interest in this material has increased. The studies ofHisaw, Velardo & Goolsby (1954) and Huggins & Jensen (1955) were stimulated by data that showed that the marked rise in oestrogens excreted during later pregnancy, and during the luteal phase of the menstrual cycle, is largely the result of changes in oestriol concentration (see Merrill, 1958, for review, and particularly the recent papers by Brown, 1955, 1956, 1959 a, b). Hisaw et al. found that oestriol would inhibit the uterine growth stimulated by either oestrone or oestradiol-17 (3 in castrate adult rats, and Huggins & Jensen extended the study to the effects of oestriol and related agents on oestrone-induced uterine growth of young hypophysectomized rats. Systemically, oestradiol-17p, oestrone and oestriol, tested in pairs, had simple additive relationships when rat-vaginal-smear changes were employed as an index of effect (Claringbold, 1955; Edgren & Calhoun, 1957a), although they were mutually antagonistic by the intravaginal route. It has long been known that progesterone is a potent inhibitor of oestrogen-stimulated responses of various types (Roberts & Szego, 1953). However, when Huggins