540 



PHYSIOLOGY OF COXADS 



VIII. Concluding Comments 



From what has been written here it is 

 readily apparent that present knowledge of 

 the mechanisms controlling the reproductive 

 cycle is extremely spotty. The number of 

 assumptions necessary to knit the various 

 items of factual information into an orderly 

 pattern is disturbing. In spite of a volumi- 

 nous literature which has grown during the 

 last 60 years, we are really only a few steps 

 ahead of our predecessors at the turn of 

 the century in terms of fundamental under- 

 standing. A brief recounting of some of 

 these steps may be desirable. 



The first three decades saw the gradual 

 development of proof that the ovary is a 

 gland of internal secretion as well as the 

 producer of eggs, governing the uterus and 

 other accessory organs by secretion of hor- 

 mones into the blood stream. For a while it 

 seemed that the events of the reproductive 

 cycle could be neatly explained, with the 

 ovary in the capacity of controlling agent. 

 Yet there were indications that the ovary 

 itself is not independent. As early as 1909- 

 1910 (Aschner; Crowe, Gushing and Ho- 

 nuins) it was noted that destruction of the 

 hypophysis is accompanied by atrophy of 

 the gonads and reproductive tract. In 1927 

 the separate investigations of Smith and 

 Engle and of Zondek and Aschheim demon- 

 strated conclusively that function of the 

 ovary depends vitally on the anterior hy- 

 jiophysis. Promptly it was learned that the 

 hypophyseal secretion of gonadotrophic 

 hormone is in turn modified by estrogens. In 

 the early 1930's the "push-pull" hypothesis 

 of pituitary-ovarian interaction was sepa- 

 rately stated by Brouha and Simonnet and 

 by Moore (see Moore and Price, 1932). 

 Modified in detail as new facts appeared, 

 this hypothesis is held to the present day in 

 some quarters as a simple exi)lanation of 

 how the cycle comes about in polyestrous, 

 continuous breeders in which ovulation takes 

 l)lacc spontaneously. Much of the investiga- 

 tion of pituitary-ovarian i)hysiology during 

 the 1930's was performed within the frame- 

 work of this hypothesis. 



For seasonal breeders and reflex ovulators, 

 however, the assumption was necessary that 

 special controlling mechanisms are super- 

 imjiosed. It bccaiiie iccognizcd also that in 



some vaguely defined manner even the hu- 

 man cycle is subject to intervention of the 

 nervous system. The possible importance of 

 the hypothalamus was debated at some 

 length in the twenties. In 1932 the existence 

 of a sex center there was proposed by Hohl- 

 weg and Junkmann. In an attempt to ex- 

 plain the coital excitation of the rabbit hy- 

 pophysis which causes the liberation of 

 gonadotrophin, Hinsey and Markee (1933) 

 suggested diffusion of a chemical substance 

 from the posterior lobe to the anterior lobe. 

 Hinsey (1937) later elaborated on this pos- 

 sibility and mentioned the hypophyseal por- 

 tal vessels as a plausible route by which the 

 substance might travel. We have seen the 

 later history of these ideas. 



The "Sexualcentrum" of Hohlweg and 

 Junkmann was proposed as a mediator of 

 the effects of estrogen on the anterior hy- 

 pophysis of rats. Westman and Jacobsohn 

 (1936-1940), on the other hand, believed 

 that through its stalk connection with the 

 hypophysis the rat hypothalamus governs 

 gonadotrophin synthesis, not release. The 

 latter they regarded as a direct effect of es- 

 trogen on the gland. These views did not 

 afford a common basis for spontaneous and 

 refiex ovulation. 



Schweizer, Chari])i)er and Haterius 

 ( 1937) offered the first surmise of similarity, 

 after finding that guinea pigs bearing intra- 

 ocular pituitary grafts developed persistent 

 estrus and large follicles that failed to go 

 through maturation changes. Their feeling 

 was that the normal connection of hypophy- 

 sis with hypothalamus may be necessary for 

 cyclic liberation of LH. Almost concur- 

 rently, Dempsey (1937) expressed a similar 

 view as one alternative explanation of his 

 experimental results with the guinea i)ig cy- 

 cle. Suggesting cautiously that release of 

 luteinizer may be brought about l)y a 

 "rhythmic discharge" from the central nerv- 

 ous system, he went on to mention the "pos- 

 sibility that a high level of oestrin is neces- 

 sary but not directly responsible for the 

 release of luteinizer" (italics added). From 

 this it is only a short transition to certain 

 concepts set forth in the present exposition. 



Accoi'ding to current views: (1) Reflex 

 ovulation and spontaneous ovulation alike 

 are go\-enicd by a liypothalamo-pituitary 



