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Removal of the right ovaries of 160\p=n-\180 g. rats was followed in 2 weeks by a hypertrophy of 55 % of the left ovary. This postoperative growth was prevented by the administration of various natural and synthetic steroidal hormones, which were compared at daily doses estimated to produce a 100 % block of the hypertrophy. The following steroids, together with approximate ED 100, were studied: oestrone, 17\m=.\8\g=m\g.;oestradiol-17\g=b\,20\m=.\4\g=m\g.; oestriol, 95\ m=. \ 5\ g=m\ g.; norethynodrel, 72\ m=. \ 5\ g=m\ g. ; progesterone, 3630\g=m\g.;testosterone,436\g=m\g.; norethisterone, 479\g=m\g.;norbolethone, 155\g=m\g. At doses above ED 100 the natural oestrogens and norethynodrel produced a secondary cycle of ovarian growth, whereas the \g=D\4-3-oxosteroids depressed ovarian size further. Hemicastrated rats had histologically normal ovaries which contained larger numbers of corpora lutea than those of the intact controls. All compounds appeared to increase follicular development at the ED 100 level; the higher doses of the oestrogens and norethynodrel stimulated excessive luteinization, whereas the \g=D\4-3-oxosteroids inhibited luteal development and produced large vesicular and cystic follicles.

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\g=a\-Methylallylthiocarbamoyl-2-methyl-thiocarbamoylhydrazine (ICI 33828) is a non-steroidal inhibitor of gonadotrophin production, acting presumably on the pituitary or hypothalamus (Paget, Walpole & Richardson, 1961; Parkes 1963). We have recently examined ICI 33828 in an assay for gonadotrophin blockade based upon prevention ofthe compensatory hypertrophy that follows unilateral ovariectomy in rats (Peterson, Edgren & Jones, 1962, 1964.Following methods described previously, female Charles River rats (160\p=n-\180g.) were hemicastrated on the first day of the assay; administration of the compound was begun immediately and continued daily for 14 days. At autopsy on day 15 the ovaries were removed, cleaned and weighed on a torsion balance. Selected ovaries were prepared for histological examination. Groups of oil-treated intact and operated rats controlled each experiment, and the difference in left ovary weight between these groups was employed as a criterion for evaluation of the effect of the compound. The compound was administered as a corn oil suspension. ICI 33828 prevented the compensatory hypertrophy that followed hemicastration in controls. The percentage changes in ovarian weights were fitted to linear regressions using the method of least squares (Table 1); and the ED 100 values, the doses that completely prevented the postoperative hypertrophy of the ovary, were calculated. Given subcutaneously, ICI 33828 appeared to be about 2\ times more potent than Table 1. Regression formulae, and ED 100 values for prevention of ovarian hypertrophy with ICI 33828 Standard error 95 % confidence Regression formula N* Dose range of slope ED 100 limits Subcutaneous administration: ml3-^S)j/t = 246-4-120-9 log dose 7(2) 0-1-10 11-3 733 701-6-764-4Gavage tr\ = 243-4-106-4 log dose 5(2) 0-3-3 8-7 1690 1662-3-1717-7 * Number of groups of 5-8 rats employed in the calculation of the dose-response curve ; the figures in parentheses indicate the number of separate tests in which these were examined. f y = percentage change in ovarian weight.

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