DISCUSSIONS 



Dr. Frederick Hisaw: I notice that we have only a few minutes before closing time so 

 I shall be as brief as possible. 



First, I should like to call Dr. Sturgis' attention to two papers, if he is not already 

 acquainted with them. One is by Dr. I. G. Schmidt (Am. J. Anat. 71, 245, 1942), who 

 made a thorough study of follicular development during the estrous cycle of the 

 guinea pig, and the other is a similar study of the rat by Dr. Charles E. Lane and 

 F. R. Davis {Anat. Rec. 73, 429, 1939). 



In connection with Dr. Rock's discussion I should like to mention some unpublished 

 observations by F. L. Hisaw, Jr. on the effects of progesterone on the menstrual cycle 

 and ovulations in monkeys. We have several adult monkeys {Macaca mulalta) whose 

 menstrual cycles have been carefully recorded for several years, and these were used 

 in the experiments. The object was to find the minimal subcutaneous dose of 

 progesterone which, when given daily, would not disturb the length of a normal 

 cycle, and to determine the effect of such treatment on ovulaton. Briefly, it was found 

 that 0.25 or 0.5 mg progesterone daily, starting soon after conclusion of a menstrual 

 period, did not influence the time of appearance of the next expected menses, nor was 

 there an effect on subsequent normal cycles. However, 0.75 mg daily seemed to 

 produce an increase in length of the cycle. Laparotomies performed at a time corre- 

 sponding to the middle of the luteal phase of a normal cycle showed that one animal 

 out of six given 0.25 mg progesterone ovulated, and ovulation did not occur in eight 

 animals given 0.5 mg. This seems to suggest that it might be possible to give progesta- 

 tional compounds to women in amounts sufficient to inhibit ovulation and not modify 

 the length of the normal menstrual cycle. 



Dr. Rock and Dr. Pincus have mentioned that in their experiments better results 

 were obtained when estrogen was given concurrently with their progestational 

 compounds. By this they mean, as I understand, that breakthrough bleeding during 

 a treatment is less likely to occur under these conditions. This probably is due to 

 two different effects, depending of course on dosage. It is well known that small doses 

 of estrogen greatly facilitate the action of progesterone on the endometrium, and also 

 these two hormones, when given concurrently, more effectively inhibit secretion of 

 pituitary gonadotropins than either alone. Castrated monkeys on 10 /ig of estradiol 

 daily rarely show breakthrough bleeding even though the treatment is continued for 

 a period of months, and the daily dose of progesterone is approximately 1 .5 to 2.0 mg. 

 Such treatments do not prevent the appearance of "castration cells" in the pituitary, 

 and gonadotropin content is correspondingly high. However, at the conclusion of 

 such treatments, if both hormones are given at the same dosage for an additional 

 twenty days, the gonad-stimulating capacity of the pituitary is almost depleted. 

 (Salhanick, H. a., F. L. Hisaw and M. X. Zarrow, J. Clin. Endocrinol. & Metab. 

 12, 310-320, 1952.) 



Dr. Warren O. Nelson: In these closing minutes I should like to devote discussion 

 primarily to Dr. Rock's presentation. There are, however, two other points that I 

 should like to make in connection with the earlier papers. 



During this meeting, we have considered occasionally, but only occasionally, the 

 important question of the relationship between the gonadotropic hormones and 

 estrogen production. This point arose this morning in connection with Dr. Gemzell's 

 presentation and it was evident, I believe, that the question as to whether FSH or LH 

 or a combination of the two is involved in the secretion of estrogen by the ovary 

 remains unresolved. 



I think this relationship is much clearer in the case of the testes, where there seems 

 to be little doubt that LH is the factor important in the production of the steroid 

 hormones. There should no longer be serious doubt that steroid hormone production 



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