Discussions 1 87 



Chairman Hisaw : The session is now open for general discussion of the papers of this 

 morning. 



However, if there is no objection I might start things rolling by mentioning one or 

 two thoughts that have entered my mind. Several years ago Dr. A. Albert and I had 

 an opportunity to make observations, of a rather general nature, on ovulation in the 

 smooth dogfish (Mustelus canis). Ovulation occurs in the vicinity of Woods Hole, 

 Massachusetts, during the last of June and the first of July. Approximately 6 to 12 

 mature follicles are situated far apart on a very large ovary and apparently one or two 

 ova are ovulated at a time. The intervals between ovulations are probably quite long 

 as each ovum must be provided with an elaborate membranous capsule. After ovulation 

 has begun and one or more eggs have been released, hypophysectomy prevents further 

 ovulation, which can be initiated by implanting pituitaries from other fish. I mention 

 this with the thought that the smooth dogfish may be a suitable animal to use in the 

 study of ovulation. 



I also should like to mention some recent experiments by Mr. R. D. Lisk, a student 

 in our laboratories, on effects of implanting fine needles containing estradiol-lVp in 

 different areas of the hypothalamus of sexually mature rats. The needles were fashioned 

 from 27-gauge hypodermic needles. The estrogen was warmed to the point of melting 

 and only the amount that could be drawn into the needle by capillary attraction was 

 used. Under this condition the hormone available to the region in which the needle 

 was implanted was the small amount that dissolved out from the tip end of the needle. 



When such implants were made in the area of the arcuate nucleus estrous cycles 

 ceased and after thirty days the uterus resembled that of a castrated animal. The ovaries 

 contained no large follicles and the interstitial tissue was atrophic. Similar effects 

 were produced in the male in which, after thirty days, the atrophy of testis, prostate 

 and seminal vesicles approached that found about thirty days after hypophysectomy. 

 It is of interest that such implants in other areas of the hypothalamus did not produce 

 these effects in the male but in the female such implants in the mammillary bodies 

 were about as effective as those in the arcuate nucleus. 



Dr. William F. Ganong: These results are reminiscent of experiments reported by Flerk6 

 and Szentagothai {Acta Endocrinol. 26, 121, 1957) in which implants of ovarian 

 tissue were made in the anterior hypothalamus in rats, and extreme atrophy of the 

 uterus resulted. Control implants of other tissues were ineffective. These and other 

 experiments suggest that estrogen feeds back to the anterior hypothalamus to inhibit 

 FSH secretion. Maybe Dr. Harris would comment on his work on stilbestrol 

 implantation in cats. 



Dr. Geoffrey Harris: I believe the work you mention was that of Flerk6 who transplanted 

 minute fragments of ovarian tissue into the hypothalamus. If these transplants were 

 placed near the paraventricular nuclei, atrophy of the uterus ensued. Similar transplants 

 into the mammillary body or hypophysis, or liver grafts near the paraventricular 

 nuclei, did not have this effect. From this and other experiments Flerkd concluded 

 that the action of estrogens in inhibiting FSH secretion is on some nervous structure 

 in the paraventricular region of the anterior hypothalamus. 



The question of hypothalamic localization of endocrine functions can certainly be 

 very difficult. Donovan and van der Werff ten Bosch, whose work was discussed this 

 morning, were unable to localize their lesions to any precise hypothalamic structure. 

 The effective lesions were, however, situated in the anterior hypothalamus. I think that 

 the suggestion of Dr. Vaughan Critchlow, that these lesions may be interrupting some 

 diffuse fibre system, such as the stria terminalis, may well be important in this respect. 

 The problem of the site of lesion in the hypothalamus which results in precocious 

 puberty was raised by Dr. Ganong this afternoon, while Dr. Sawyer this morning 

 discussed the areas of the hypothalamus involved with patterns of sexual behavior. 



In respect of estrous behavior in cats, Dr. R. P. Michael and myself found a few 

 years ago (Harris, G. W. and R. P. Michael, /. Physiol. (Lond.) 142, 26P (1958)) that 

 implants of minute amounts of stilbestrol, fused onto the end of a needle which was 



