Discussions 243 



in the testes occurs in the Leydig cells. These are influenced by LH (or ICSH) and 

 by the same token, then, LH would be expected to be the factor that stimulates the 

 production of estrogen, and also of androgen in the ovary as well as the testis. Since 

 recent evidence indicates the source of estrogen production probably occurs by way 

 of an androgenic precursor, it follows that LH is the probable factor of importance. 



I believe all of us should have liked to have heard more from Dr. Gemzell about 

 the direct effect of steroids on ovarian function. The evidence that he did present 

 suggests that there may be a direct inhibitory effect of progesterone on ovarian response 

 to FSH, but perhaps it might also be interpreted on the basis of progesterone inhibition 

 of endogenous gonadotropin. It must be remembered that the subjects had pituitaries 

 and that their pituitaries contributed to the total response or lack of response. 



Finally I should like to comment on some of the interesting compounds discussed 

 by Drs. Rock and Pincus. We have had reason to be concerned with them because 

 of our interest in procedures that interfere with fertility, and in one way or another we 

 have examined all of these compounds. 



A consideration that has commanded our interest has been their gonadotropin 

 inhibiting properties. Our evaluation of this activity has involved a procedure that we 

 believe gives a fairly good idea about the relative inhibition of FSH and LH. We have 

 used the 30-day-old male rat, treated 30 days. The 30-day-old male rat is immediately 

 pre-pubertal and during the next 30 days would normally become an adult male. 

 However, by suitable treatment with an effective inhibiting compound, he can be kept 

 in the immature state, so far as reproduction is concerned, for 30 days or as long as 

 might be desired. 



As I have said, we can obtain a good index of the relative suppression of the two 

 gonadotropins. The weight of the testes provides excellent evidence of the effect, or 

 lack of effect, of FSH. The accessory organs, such as the prostate, seminal vesicles, 

 and epididymis, reflect the presence or absence of adequate amounts of LH. 



In general, we have found that effective gonadotropin inhibiting compounds require 

 about twice the dose for FSH inhibition that they do for LH suppression. This has 

 been a consistent finding. 



The one point that I should like, finally, to make with regard to the gonadotropin 

 inhibiting effects of these compounds is that the important point in the inhibition of 

 ovulation may not be so much a matter of relatively complete inhibition of total 

 gonadotropin production as it is the relative inhibition of FSH or LH. Since LH 

 appears to be inhibited more readily by the steroids in question, it would seem likely 

 that ovulation might be interfered with by reduction in LH without detectable reduction 

 in total gonadotropins. 



This consideration recalls the studies that Dr. Rock and Dr. Pincus made with 

 progesterone in the inhibition of ovulation. In the women so treated, about 80 % of 

 the cycles were believed to be anovulatory. Where highly effective gonadotropin 

 inhibitors, such as Enovid and Norlutin, are concerned, gonadotropin inhibition may 

 be so complete that the question of relative inhibition is of little importance. In the 

 case of progesterone inhibition, I daresay that total inhibition was not obtained and 

 that the question of relative inhibition assumes importance. In all likelihood the 

 partial reduction of LH secretion was sufficient to prevent ovulation in some cases. 



Chairman Astwood : Our time schedule has now run out, and I am afraid I shall have to 

 turn the meeting back to Dr. Villee, who wants to make a few remarks. Before so 

 doing, I want to voice the opinion of those preseiit that Dr. Villee has done a marvellous 

 job in arranging the Conference, and we are all sufficiently grateful to him to acclaim 

 this event. (Applause.) 



Dr. Claude Villee: Thank you very much. Dr. Astwood, for your very kind remarks. 

 I want to express on your behalf our deep appreciation to the Association for the 

 Aid of Crippled Children and to Mrs. William FitzGerald, who is here, for making 

 this Conference possible. Many of you have told me how much this Conference has 

 meant to you, and I hope that Mrs. FitzGerald will take back to her Board the 

 consensus of opinion that it was a most worthwhile way to spend a pleasant week-end. 



