52 Discussions 



Dr. Miriam E. Simpson: Although it is commonly assumed that some ICSH must be 

 present with FSH before full maturity of the follicles and estrous response can be 

 elicited, nevertheless the exact amount of ICSH needed is not known accurately. I 

 think we arc agreed that a follicle needs a vascular envelopment for development, and 

 this is supplied by the theca. 



Chairman Creep: It seems that the importance of balance is not just at the time of 

 ovulation, but long before that. You have to have the proper preparation all the way 

 along, in order to get really effective ovulation. 



Dr. Somers H. Sturgis: I would like to ask Dr. Pincus a question. I gather that the 

 steroids were given just after mating so that you had 10 hr in which they had to work, 

 presumably to prevent ovulation. This would seem to me to be a very short time for 

 these compounds to work, particularly those that were given by the oral route. It 

 suggests some mode of action other than through pituitary inhibition. What about 

 the possibility of some direct action on the follicles themselves? We don't know very 

 much about the activity of an ovarian steroid as estrogen or progesterone on the 

 ovary itself, yet in the hypophysectomized rat, estrogen certainly does maintain and 

 perhaps even stimulate the growth of follicles and granulosa. Last fall, Vasicka 

 reported at the American College of Surgeons some evidence for the direct action of 

 Enovid on human ovaries. In ovarian biopsies, he felt that he could show an increase 

 in follicle atresia following Enovid medication. 



In this regard, do you want to say something about the possibility of some direct 

 action of these steroids on the ovarian follicles, or do you believe that the effect that 

 you have shown us on inhibition of ovulation can and must take place through the 

 pituitary, even when giving oral preparations after mating with only ten hours for 

 effective action before ovulation will occur? 



Dr. Gregory Pincus: Dr. Chang and I originally found that with progesterone, we could 

 practically invariably ovulate the animal receiving an inhibiting dose, by giving 

 gonadotropins intravenously. Whether this would be true of all the compounds we 

 have tested, I don't know. I know it is true in some cases. As to the possibility of a 

 direct influence on the ovary, this ties in with Dr. Hisaw's and Dr. Hammond's 

 discussion; it is something that fascinates me very much. 



If we had been lucky enough to find a steroid which causes ovulation, the course of 

 reproductive physiology might have changed markedly. I think that there may be 

 such a substance. 



If there is something which can stimulate ovulation, there are certainly plenty of 

 things you should be able to do to reverse such stimulation. We know that steroids can 

 act as antagonists to each other in many situations. We have tried to find some 

 evidence for direct action of steroids upon the ovaries in studies with the mouse. 

 What we did was to use PMS and HCG to ovulate the mice, administer the steroid, 

 and then see if ova were produced. 



The most potent ovulation inhibitors proved to be reserpin and chlorpromazine. 

 So we probably weren't by-passing the pituitary of the animals but affecting an endo- 

 genous factor that acts with the administered gonadotropins. Certain of the steroids 

 also were active in inhibiting ovulation. 



The last point I want to make is in reference to Dr. Hisaw's remarks. As far as the 

 genesis of hormonal steroids is concerned, in every species of mammals studied so far, 

 the process is identical. The major precursor is cholesterol; this is transformed to 

 A^-pregnenolone, which is the parent of all the steroid hormones. 



One of the possibilities very much overlooked is that some of these steroids are 

 mitosis-stimulating and others mitosis-inhibiting. What relationship this would have 

 to egg development and maturation has never been studied. With modern techniques, 

 one ought to be able to isolate and grow eggs to see whether there are inhibiting and 

 stimulating steroids. 



Chairman Creep: Is there a biologist in the house? I would like to have someone comment 

 on the work of Witschi and Chang. 



