2 Frances Carter, Marion C. Woods and Miriam E. Simpson 



in primates share the defects common to all efforts which have been made in 

 the last 30 years to obtain an understanding of the pituitary factors necessary 

 for ovulation (9, 10, 19, 20, 29). The presence of a pituitary in the recipients 

 complicates the response of normal animals to any gonadotropin adminis- 

 tered. All efforts have been handicapped by the lack of pure gonadotropins. 

 In the studies of van Wagenen and Simpson, to which reference has just been 

 made, neither hypophysectomized monkeys nor single pure gonadotropins 

 were available. The products from sheep pituitaries which were injected were 

 prepared by repeated ammonium sulfate fractionation of 40% ethanol extracts 

 of whole glands. The preparations from monkey pituitaries were lyophilized 

 40% ethanol extracts of anterior lobes. No further purification could be 

 undertaken at the time due to the scarcity of material. It was therefore evident 

 that we were not ready for sufficiently exacting experiments in the primate. 



Hypophysectomized Rat 



Meanwhile studies were in progress in which hypophysectomized rats 

 were being used as the experimental animal (2). These animals were available 

 in adequate numbers, and their use avoided the confusion introduced into 

 interpretation of the results by contributions from the recipient's pituitary. 

 These studies, like those in the primate, were subject to the criticism that 

 no completely pure pituitary gonadotropins were available, so that the 

 proportion of the two pituitary gonadotropins, FSH and ICSH, tentatively 

 regarded as essential for ovulation, could not be precisely determined. An 

 attempt will be made, however, to define the status of our knowledge 

 regarding the pituitary factors necessary for ovulation in the rat as determined 

 with the purest sheep pituitary FSH and ICSH now available. 



In the rat, as in other species investigated, there was no difficulty in develop- 

 ing follicles, or in luteinizing them, but conditions necessary to cause release 

 of ova were more exacting. When these conditions were determined for the 

 hypophysectomized rat, it was found that superovulation was typical, a 

 characteristic observed repeatedly in experimental induction of ovulation 

 with exogenous gonadotropins in normal animals of many species. The 

 shedding of a number of ova greater than that characteristic for the species 

 is in itself an abnormal phenomenon, and the question must be raised 

 eventually as to the significance of the number of ova shed, though no 

 attempt will be made here to evaluate this matter. 



In order to analyze which pituitary hormones are needed, and in what 

 proportion they must be present, it was necessary first to determine a set of 

 conditions under which ovulation might reliably be obtained in the hypo- 

 physectomized rat. These standard conditions were determined by the use 

 of a follicle-stimulating preparation from sheep pituitaries which was obtained 

 by repeated refractionation of an 0.8 saturated ammonium sulfate (AS) 

 fraction from which a number of fractions had already been removed at 



