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A considerable amount of work has been done on the metabolism by living animals of oestrogens, both natural and synthetic, but, as pointed out by Dodds, Folley, Glascock & Lawson (1958), the doses given have nearly always been very large compared with the physiological dose. This has been necessary because the methods available for the detection of the oestrogens or their derivatives were relatively insensitive even when labelling with 14C was used (Twombly, 1951; Twombly & Schoenewaldt, 1951; Hanahan, Daskalakis, Edwards & Dauben, 1953; Budy, 1955). Apart from the work of Dodds et al. (1958) (see below) the smallest doses have been used by Hanahan et al., who gave [14C]_ stilboestrol to rats in doses of 5 ,ug., which is still more than ten times the physiological dose. It has been generally concluded that these oestrogens do not accumulate in organs such as uterus, vagina, mammary gland and pituitary gland, which respond to them physiologically. If this is so it would be necessary to attribute the response of these organs to some such mechanism as a selective sensitivity to the circulating oestrogen. Glascock (1956) pointed out that by using tritium as a labelling agent very high specific activities are attainable and that this is extremely important when substances biologically as potent as the oestrogens are studied. In the rat, for example, 0-2jug. of hexoestrol administered subcutaneously has a detectable action on the vagina (Dodds et al. 1944), whereas about 2L0 of the subcutaneous dose is effective when administered locally to the vagina (Emmens, 1940-41). This indicates that perhaps only a very small portion of a subcutaneous dose of oestrogen need reach the responding organs and that extremely sensitive methods of detection, and the use of the smallest effective doses, are probably necessary if any selective localization of the oestrogen in these organs is to be demonstrated. Dodds et al. (1958) traced the excretion of microgram doses of tritium-labelled hexoestrol (specific activity about 107 counts/min./pg.) in rats and rabbits, but did not measure the radioactivity of body tissues. Subsequent studies with rats (M. Gabr & R. F. Glascock, unpublished work) indi* Present address: Department of Biochemistry, University of Wisconsin, Madison 6, Wisconsin, U.S.A.

Selective accumulation of tritium-labelled hexoestrol by the reproductive organs of immature female goats and sheep