Studies on urinary oestrogens

• Main Author: Watson, Elizabeth J. D.
• Published: University of Edinburgh 1957
• Subjects: 571.74
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.663528

For many years, ovariectomy has been known to cause cessation of oestrus and modification of secondary sex characteristics in animals. In 1913, Fellner observed that transient oestrous symptoms could he produced by injecting an ovariectomized animal with extracts of ovaries. These oestrous symptoms could be followed in the rat by observing histological changes in the vaginal epithelium and in 1923 this keratinization of the vaginal wall was used in the development by Allen and Doisy (1923) of a quantitative test for oestrogenic substances. Four years later, using this method of bioassay, Ascheim and Zondek (1927) discovered that extracts of human pregnancy urine possessed much greater oestrogenic activity than did ovarian extracts. This observation led to a closer examination of pregnancy urine and within two years the first crystalline oestrogenic substance, oestrone (oestra-1:3:5-triene-5-ol-17-one), was isolated from urine independently by two groups of workers - Doisy, Veler and Thayer (1929) and Butenandt (1929). In the following year, oestriol (oestra-1:3:5-triene-3:16α:17β-triol) was isolated from the same source first by Marrian (1930) and soon after by Doisy, Thayer, Levin and Curtis (1930), In 1933, Schwenk and Hildebrandt succeeded in reducing oestrone to an oestradiol (later shown to be oestradiol-17β (oestra-1:5:5-triene-3:17β-diol)) which was found to possess higher oestrogenic activity than either oestrone or oestriol. As a result of this finding, oestradiol-17β was adopted as the probable active principle secreted by the ovaries. Although this oestrogen was isolated from pregnant mares' urine (Wintersteiner, Schwehk and Whitman, 1935) and sows' ovaries (MacCorquodale, Thayer and Doisy, 1936) it was not until 1939 that Smith, Smith, Huffman, MacCorquodale, Thayer and Doisy isolated it from human pregnancy urine. Between 1939 and 1953 no further metabolites of oestrogen metabolism were isolated from urine although a number of investigators reported the presence in various urine extracts of unknown substances whose chemical and physical properties suggested that they might prove to be derivatives of known oestrogens (Pincus and Pearlman, 1943; Serchi, 1952; Zondek and Finkelstein, 1952; Migeon, 1953; Braunsberg, Stern and Swyer, 1954). Only one of these led to the actual isolation of an oestrogen metabolite, viz. 16-oxo-oestrone (oestra-1:3:5-triene-3-ol-16:17-dione) which Serchi (1953) obtained in crystalline form from the urine of non-pregnant women.