THE ROLE OF STEROIDS IN THE CONTROL 

 OF MAMMALIAN OVULATION* 



Gregory Pincus and Anne P. Merrill 



The Worcester Foundation for Experimental Biology 



Shrewsbury, Massachusetts 



We have previously described methods for determining the effects of various 

 compounds on copulation-induced ovulation in the rabbit (1,2,3). Our 

 standard procedure is to administer the test substance to a post-partum 

 female rabbit and then mate her to a male of knovv'n fertility 1 8 to 24 hr later. 

 On the day following the mating the occurrence of ovulation is ascertained 

 by examining the ovaries for rupture points at laparotomy. The occurrence of 

 pregnancy in such mated rabbits may easily be determined by palpation of 

 uteri for implantations at the tenth to fourteenth day after mating. In order to 

 obtain a preliminary idea of the effectiveness of any given compound, our 

 usual procedure is to administer a dose of 10 mg per animal to each of five 

 post-partum females. In view of the fact that approximately 90% of untreated 

 post-partum rabbits ovulate under these conditions, the absence of ovulation 

 in all of the five test animals is highly significant; if one out of five ovulates 

 the effect is considered marginally significant. 



In Figs. 1 through 12 are presented the structural formulae of those steroids 

 which have given some indication of acting as ovulation inhibitors when 

 administered to groups of five post-partum rabbits. At the dosage underlined 

 with a soHd line, all animals failed to ovulate; at the dosages underlined with 

 a broken line, marginally significant frequency of inhibition occurred. 



Among the estrogens (ring A unsaturated) and their derivatives, nine 

 compounds gave indication of activity (Figs. 1 and 2). Consistent evidence of 

 inhibition following subcutaneous injection at various dosages is given by 

 estrone (IV, Fig. 1) and I7a-ethyl-I7/3-estradiol (II, Fig. 1). Estradiol (I, 

 Fig. 1) itself, which we expected to be quite a potent inhibitor and which was 

 thus tested at relatively low dosages, gave a marginally significant effect at 

 0.1 mg per rabbit by mouth but not at 0.5 mg per rabbit. All of the other 

 compounds listed in Figs. 1 and 2 appear to be of rather low potency. 



* Investigations described in this paper have been conducted with grants-in-aid from 

 G. D. Searle & Company and the Population Council, Inc. 



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