1 1 8 Discussions 



I feel that I should do something to justify my presence by making a few remarks 

 now regarding what we have heard this morning. We have had some most fascinating 

 papers which fully maintained the high standards set by the papers yesterday afternoon. 



I was most interested in Dr. Sawyer's paper, and in this connection I would like to 

 refer to some observations on the ewe, which were reported in Nature last August 

 by Raeside and McDonald (Nature 184, 388, 1959), which seem to fit in very well 

 with his conclusions. As you know, the ewe is a seasonal breeder and these workers 

 investigated the threshold doses of estrogen required to induce estrus in spayed ewes 

 primed with progesterone. They found that less estrogen was required for this response 

 during the breeding season than during anestrum. This would seem to point to the 

 existence of a built-in rhythmic variation in the sensitivity of the so-called hypo- 

 thalamic "sexual center" which controls estrous behavior. On the other hand, the 

 threshold doses of estrogen necessary to induce characteristic changes in the chemical 

 properties of the cervical mucus were the same regardless of whether the treatment 

 was given during the breeding or non-breeding season. Thus peripheral responses to 

 estrogen appear to be constant irrespective of season. 



Coming to Dr. Hansel's contribution, which interested me a great deal, I find it 

 very difficult to reconcile his results with those of other workers and of ourselves on 

 small animals. I think it is true to say that in laboratory animals, certainly rats and 

 rabbits, the experiments with oxytocin almost exclusively point to the release of 

 prolactin rather than gonadotropin. The best known exception is provided by the 

 results reported in Japan by Shibusawa and his collaborators who claim that oxytocin 

 releases gonadotropins as judged by an increased excretion of 1 7-ketosteroids in the 

 urine. Dr. Hansel himself, in a recent review, has ably discussed the Japanese results 

 and I thought he dealt with them admirably without appearing to be unduly critical. 

 Obviously, as Dr. Hansel pointed out, we cannot accept these results without further 

 confirmation. This being so, I think the balance of evidence from experiments on 

 small animals would appear, at least to me, to indicate that oxytocin, rather than 

 releasing gonadotropins, evokes the release of LTH, by which I mean prolactin. 

 How then can Dr. Hansel's interesting results be reconciled with this conclusion? 

 We know, as he made clear, that in the cow uterine interferences of various kinds 

 almost invariably cause the release of oxytocin. In passing, it might be interesting 

 in this connection to recall a curious custom practised by the women of certain 

 primitive tribes in Africa when they milk their cows. The custom is to blow into 

 the vagina of the cow just before milking, thus inflating it with air. This seems to 

 favor the occurrence of the milk-ejection reflex which, as you know, involves the 

 release of oxytocin. To return to our main theme, I cannot help wondering whether 

 Dr. Hansel's results might not be due to the presence of some polypeptide, different 

 from oxytocin but chemically related to it, which might have been present in the 

 preparations he used. In any event, I was interested in his suggestion that administered 

 oxytocin might feed back on the central nervous system. Especially is this so because 

 we have thought along these lines ourselves, in relation to our own experiments on 

 rats, in which we have evidence of prolactin release evoked by administration of 

 oxytocin. It seems quite possible that the doses of oxytocin used in Dr. Hansel's 

 experiments might inhibit the release of the animal's own oxytocin. Evidence indicating 

 the possibility of such a feed-back mechanism was provided some years ago by 

 Petersen and his colleagues (Donker, Koshi and Petersen, Science 119, 67, 1954) 

 who were studying the effects of regular injections of oxytocin in a cow just before 

 milking in order to cause more complete evacuation of the udder. When the treat- 

 ment was discontinued after 156 repetitions at hourly intervals the natural milk- 

 ejection reflex was significantly inhibited and it took some days before it returned. 



Professor Harris showed some beautiful slides and I would like to refer to one in 

 particular, the one which illustrated various types of humoral mechanisms. There is 

 one other type of mechanism which he did not include, that I have often thought 

 might apply to the anterior pituitary. This is the direct chemical action of one type 

 of cell upon another by means of a cellular secretion. Looking in a general way at 

 the picture of anterior-pituitary function, as understood at present, the secretion of 



