Discussions 221 



Dr. Janet McArthur: Dr. Parlow discussed this recently at the N.I.H. Gonadotropin 

 Workshop. He has found that the ascorbic acid depletion method is very satisfactory 

 for the assay of pituitary LH. However, there appear to be interfering substances, both 

 in plasma and urine, which prevent valid assays of the LH content of these fluids. 



Dr. Roy Hertz: I want to thank Dr. Sturgis for his paper. There is, however, one phase 

 of follicular development which I think is being largely overlooked. 



You will recall that in that day-old ovary there was represented nothing but the 

 primordial type of follicle, and we have very little knowledge actually of what trans- 

 forms the primordial follicle into an antrum-containing follicle. 



In the new-bom rat, just as in the human ovary, the ovary at birth is made up 

 entirely of such follicles in immediate juxtaposition to each other, with a very small, 

 fine stroma between them, and there is no indication of any follicular organization 

 in any part of the ovary at that time. It is not until about the eleventh day, post-natally, 

 that one begins to see the beginning of granulosa cell development and an antrum 

 formation. It is at that point that one gets the first responsiveness to gonadotropin. 

 Up to eleven days, you can give massive doses of gonadotropin to the new-bom rat, 

 and get no response, until the follicle has become organized sufficiently to have an 

 antmm of its own. 



In the rabbit, this process takes ten weeks post-natally. So for ten weeks, during the 

 post-natal period, we have this pre-pituitary process going on, with follicular differ- 

 entiation, and the development of initial sensitivity to stimulation. 



We became interested in what was involved in this process, and what role the pituitary 

 may play in the process, and therefore grafted day-old ovaries under the kidney 

 capsule of the mother of the young. She had just given birth to these babies. We 

 then hypophysectomized the mother immediately. We found that this entire process 

 of sensitization to gonadotropic hormone is independent of the pituitary. It goes 

 along well, in a completely hypophysectomized female. It is not dependent upon 

 any specific factor from the host; it seems to proceed quite independently of 

 any known pituitary factors. 



We do see that during this process there is a substantial mortality in the primordial 

 ova. Their numbers progressively decline. There is something which they are contri- 

 buting, or which their mortality is contributing, to the process. 



This is an area which I feel, from a clinical standpoint, also, is being neglected. 

 For instance, we now have four patients with ovarian hypoplasia, and biopsies of 

 their ovaries show the identical histological picture that you have described for the 

 ovary of the new-bom. 



It seems that in such individuals, this pre-pituitary process has gone up to the point 

 of gonadotropin sensitization. These patients have ample gonadotropin in the urine, 

 actually high levels, and yet the ovary has not gotten to the point of responsiveness. 



Dr. Gregory Pincus: We have also been conducting some studies with human pituitary 

 FSH. The sample we used was prepared by Dr. Li and is very low in LH. With 

 this we did not get an increase in estrogen production until HCG was also given. 

 I would like to ask Dr. Gemzell whether he observed any estrogen production when 

 he used his very highly purified FSH, which is probably more nearly free of LH. 



Dr. Carl Gemzell: We have not done any experiments with the highly purified FSH as yet. 

 The chemist who is woiking on it is more interested in finding out something about 

 its physical-chemical properties; but I hope that when he is through we will be able 

 to test it. 



I don't know how much LH there is in Dr. Li's preparation of FSH. It is very likely 

 that the contamination with LH is of great importance. 



I haven't had any experience with the preparations of various activities, so I can't 

 answer your question. 



