1 S6 Discussions 



season. In such cases it is often possible to obtain a fertile mating. In some exp>eriments 

 we did ten years ago in our laboratory, we found that a single injection of 1200 I.U. 

 PMS into anestrous goats was often followed by fertile mating. I think this occurred 

 in about 22 "„ of the females injected. 



In other experiments on the quantitative effects of PMS on the ovaries of virgin 

 goats, we found that small doses (about 400 I.U.) of PMS would cause ovulation 

 without estrus, while it took between 1000 and 1200 I.U. to cause noticeable effects 

 on follicular growth. 



Thus the female goat seems to be somewhat different from her near relative, the 

 ewe, in the following respect: there is, in many cases, no need to give two injections, 

 spaced a cycle apart, in order to achieve out-of-season breeding. 



Dr. Villee: I should like to ask Dr. Nalbandov whether he believes the results he obtains 

 are due to a direct action of the protein hormones on the hen's ovaries, or whether 

 some steroid might intervene between the protein hormone and the tissue. 



Dr. Nalbandov: May I start with Dr. Chang's comments. The references to the role of 

 "atresia", "necrosis" and "ischemia" in the ovulatory process should be regarded as 

 relative and not absolute terms. When I say that ischemia precedes the rupture of 

 the follicle, I don't mean to imply complete cessation of blood flow but a reduction 

 in the rate of flow and in the amount of blood. I agree that if one were to tie off the 

 blood supply of an ovary or of an individual follicle these structures would invariably 

 and inevitably disintegrate rapidly. This is not a physiological process and you cannot 

 expect follicles or ovaries to continue normal function under these conditions. You 

 next stated that if the proposed theory is correct, one should expect ovulation to occur 

 in the hypophysectomized animal without exogenous hormone. According to the 

 theory proposed ovulation does not follow a hormonal vacuum (as in hypophysectomy), 

 but is caused by a relative reduction in the amounts of hormones made available to 

 the follicle. This reduction in available hormone may be caused by a reduction in 

 blood flow or, as Dr. Meyer suggests, may be due to the increase in the turgidity and 

 fullness of the follicle which leads to a constriction of blood vessels and a reduction 

 in the amount of blood flowing through. Referring to the slide shown by Dr. Meyer, 

 I should like to suggest that his data support the contentions outlined by me, since the 

 maximum ovulation rate occurs about 18 hr (and perhaps even later) after the injection 

 of the ovulator, instead of occurring at the usually accepted time of about 10 hr after 

 LH injection. 



In reply to the last question I should like to confuse the issue by presenting a few 

 preliminary observations on the role of progesterone in the ovulability of eggs. I 

 remind you of the statement that in the normal laying hen it is never possible to induce 

 the ovulation of obviously immature follicles with exogenous gonadotropins. However, 

 tiny immature follicles can be induced to ovulate with relative frequency in intact 

 hens if no treatment other than progesterone is given. Furthermore, hypophysectomized 

 hens can be given a minimum dose of LH which is adequate to induce a single ovulation. 

 If we now add progesterone to this minimum dose of LH, we can occasionally induce 

 multiple ovulations. In this last experiment progesterone does not act on the missing 

 pituitary gland, but it could act on the hypothalamus causing it to release ovulation- 

 inducing substances which cooperate with exogenous LH to increase the frequency 

 of follicles ruptured. It is, of course, also possible that in both experiments progesterone 

 acts on the follicle directly and increases its sensitivity to LH. Which interpretation is 

 the correct one, remains to be seen. 



Dr. Robert Noyes: I would like to raise a question concerning the mechanism of ovulation. 

 Is it possible that LH acts by causing the dissolution of the granulosa? As you know 

 one can grow granulosa cells of pre-ovulatory follicles in tissue culture but this 

 becomes impossible after the granulosa cells have been exposed to LH. 



Dr. Nalbandov: This observation seems to reduce the importance of the vascular system 

 in ovulation and emphasizes the possible significanee of LH. It is obvious that a lot 

 more work is needed before the process of ovulation is completely understood. 



