50 Discussions 



The only endocrine features that seem to be common throughout the life of a 

 follicle in both vertebrates and invertebrates are the presence of steroid hormones 

 and the fact that the follicle normally ruptures. Therefore, the solution of the problem 

 of ovulation may be found by investigating the basic physiological processes that go 

 on in the follicle. There have been very few analytical efforts in this direction. Most 

 research has been concerned with the regulatory mechanisms that affect follicular 

 physiology. Those factors which originate outside the ovary are for the most part 

 timing devices to guarantee that ovulation occurs at the most favorable moment and 

 season for fertilization and survival of the embryo. It is of course a familiar fact that 

 environmental factors such as light, temperature, humidity, food, etc., can influence 

 the secretion of gonadotropins by the pituitary and it is now quite evident that these 

 effects are mediated by the nervous system. 



It is of course a familiar and interesting observation that ovarian development and 

 ovulation generally is attuned to environmental influences such as light, temperature, 

 humidity and food. These influences in vertebrates are mediated by the pituitary but 

 it is obvious that ovulation was a well-established phenomenon long before a pituitary 

 was invented. Therefore, the physiology of the follicle itself should hold the solution 

 of the problem and steroid action may be the answer. 



The research reported by Dr. Pincus deals with the most important practical problem 

 that confronts the human race today. The destiny of mankind most certainly depends 

 more on control of the world's population than it does on the curious international 

 competition now raging over such comparatively trivial things as who is to enjoy the 

 dubious distinction of being the first to get a peek at the sea's bottom or the moon's 

 backside. Even so, finding a method for the inhibition of ovulation is in reality a 

 problem in endocrine engineering which relies on basic information rather than 

 contributing to it. However, these studies have raised many important questions 

 regarding essential molecular morphology of an effective steroid inhibitor and the 

 nature of the inhibitory process. 



Chairman Creep: Dr. Folley, would you like to comment on any of these three papers? 



Dr. S. John Folley: At this rather early stage of the proceedings I do not think 

 that any comment of an all-embracing nature has occurred to me, except for one point 

 in connection with what Dr. Hammond has just said about the follicular fluid. We 

 know that, in addition to the proteins, salts and so forth mentioned by him, follicular 

 fluid also contains other substances, in particular at least two mucopolysaccharides. 

 I have often wondered if there is some connection between the fact that the gonado- 

 tropins are glycoproteins and the fact that the cells lining the follicles, at least some 

 of them, are cells which secrete mucopolysaccharides. I am afraid I cannot offer any 

 more specific suggestions about this at the present time, but it would seem to me to 

 be a point which is worth some consideration. More pertinent, perhaps, is the fact 

 that these mucopolysaccharides undergo depolymerization just before ovulation, with 

 a concomitant rise in the colloid osmotic pressure of the follicular fluid (Zacharias and 

 Jensen, Acta Endocrinol. 27, 343, 356, 1958), and one cannot help wondering whether 

 estrogen produced by the follicular cells plays any role in this as it seems to do in the 

 liquefaction of the cervical mucus at estrus. I throw this out to the meeting as something 

 which might be thought about and perhaps we might have some ideas about it. 



Chairman Creep: Is there any one who would like to comment, or is there any one who 

 would like to pose a question to any of our speakers of the afternoon ? 



Dr. Warren O. Nelson: I wonder, Cregory, harking back to your remarks about 

 inhibition of ovulation in the rat whether it would not be appropriate to take into 

 account the fact that the 19 nor-compounds behave very much, under some circum- 

 stances, as estrogens do. If they are given to adult rats corpora lutea are maintained. 

 Your objective was, of course, to examine the inhibitory activity of these compounds 

 which, indeed, are very effective gonadotropin inhibitors, but I wonder if the presence 

 of corpora lutea in animals, treated for fifteen days, would not reflect the fact that 

 corpora lutea were present at the time treatment was begun and were caused to persist 

 by treatment. 



