Discussions 53 



Dr. Sheldon Segal: I am reminded of three recent studies that bear on today's discussion. 

 The first is by Meyer and Bradbury {Endocrinology 66, 121-128, 1960), demonstrating 

 a direct effect of estrogen on growing ovaries. Using both immature and hypophy- 

 sectomized rats, they found that estrogen priming (stiibestrol) enhanced the ovarian 

 response to gonadotropin. This principle may be of significance with respect to some 

 aspects of the work reported by Dr. Noyes and Dr. Simpson. In each case, the failure 

 of the ovary to respond to stimulation could be correlated with an absence of estrogen. 

 In the experiments of Dr. Noyes, the ovarian implants were made in castrate hosts. 

 Would the addition of estrogen improve the performance of the ovarian implants? 

 Dr. Simpson reports that FSH preparations most purified and free of ICSH contamina- 

 tion (<4%) are least effective as a supplement in causing ovulation. Do these results 

 correlate with the effect of the preparations on causing ovarian estrogen production? 

 The two other studies I would like to mention deal with in vitro ovulation using 

 frog ovaries. Witschi and Chang {Endocrinology 61, 514—519, 1957) found that exposure 

 of primed segments of frog ovaries to cortisone in vitro favored egg-release. Bergers 

 and Li {Endocrinology 66, 255-259, 1960) reported that in vitro ovulation by this test 

 is induced by progesterone. ICSH and GH, from mammalian sources, induced 

 ovulation also under the conditions of the experiment. Neither study included a report 

 of the activity of estrogen in this in vitro test. It would be of interest to learn about this 

 in view of the evidence for the direct effect of estrogen on the mammalian ovary. 



Dr. Villee: I would like to ask Dr. Simpson whether she had tried to add estrogens in 

 the course of the preparation of the follicles. 



Dr. Miriam E. Simpson: Estrogens have not been injected. Furthermore, there was not 

 sufficient time to present the estrogenic properties of each of the follicle-stimulating 

 preparations injected. The purified follicle-stimulating preparations were very different 

 in regard to their ovulating capacity and eventually we will present the correlation 

 between the capacity of FSH preparations to induce ovulation and to cause estrous 

 uterine response. 



Dr. Robert W. Noyes: It always appeared to me that a follicle may make enough estrogen 

 to prepare the endometrium on its own. Occasionally, in post-menopausal women, a 

 pregnancy may occur two or three years after the last period, and you wonder if a 

 single follicle was able to make enough estrogen and progesterone to support 

 implantation and pregnancy. 



Nalbandov: In connection with Bradbury's work, it seems significant to me that the 

 doses of estrogen or stiibestrol required to produce these effects on the ovary are 

 extremely high. I believe that a minimum of 1 mg of the steroid per day must be given. 

 This fact suggests that this is not a physiological mechanism and raises the question 

 whether the effect is produced by the hormone itself or by a metabolite of these 

 substances. 



Dr. Sheldon Segal: One can't decide that issue until he does a subsequent step of making 

 local implantations of estrogen crystals or small pieces of estrogen in one ovary, in 

 relation to the next step. We will have to wait for those results before deciding whether 

 it is a physiological thing or not. 



Dr. Gregory Pincus: I would like to say one thing in regard to that. He may not be 

 using the right estrogen. 



Maybe it is natural. If you study ovarian vein blood and study the estrogens in 

 there, you would be surprised. They are not the usual estrogens, but they may be of 

 importance physiologically. 



Dr. W. R. Breneman: Perhaps I should let Dr. Segal speak on the following point since 

 I believe that the non-mammalian vertebrates provide information relative to the 

 effect of steroid hormones on the gonads. For example, in the amphibia distinct 

 primary and secondary cords usually are present in both testes and ovaries and 

 Burns demonstrated in the 1930's that sex hormones were able to regulate the 



