MAMMALIAN REPRODUCTIVE CYCLE 



523 



in the rat hypothalamus is increased also 

 by administration of estrogen or by castra- 

 tion, conditions that similarly increase 

 lihosphorus exchange (Borell and Westman, 

 1949). The ACh content is depressed during 

 pregnancy or when the rat has been in- 

 jected with progesterone. It is also lowered 

 by Pentothal anesthesia, a matter of interest 

 in relation to the fact that the barbiturates 

 suppress ovulation (see p. 526). 



The location and measurement of activity 

 in discrete nuclei and pathways are largely 

 in the future, although a beginning has been 

 made in the rabbit, cat, rat, and mouse. 

 Sawyer (1955) found in rabbits, after the 

 combined administration of pentobarbital 

 intravenously and histamine by way of the 

 3rd ventricle, that there was associated 

 with induction of ovulation a characteristic 

 change in intrinsic electrical activity of the 

 rhinencephalon, extending into the preoptic 

 area. If the olfactory tracts were cut, how- 

 ever, this activity could not be elicited and 

 ovulation failed. According to Porter, Cav- 

 anaugh and Sawyer (1954), vaginal stimu- 

 lation of estrous cats caused altered electri- 

 cal activity in two hypothalamic regions: 



(1 ) in the lateral hypothalamic area at 

 the anterior tuberal level during stimulation 

 and for 15 to 45 seconds afterward; and 



(2) in the anterior hypothalamic area near 

 the medial forebrain bundle, where response 

 was delayed as much as 5 n:iinutes after 

 stimulation. According to a i)reliminary 

 account (Critchlow and Sawyer, 1955) in 

 curarized, proestrous rats, there were i)e- 

 riods lasting approximately 20 minutes in 

 the midafternoon, during which altered 

 electrical activity appeared differentially in 

 the preoptic area or anterior hypothalamus. 



Another approach to localization has been 

 described by Hertl (1952, 1955). On the 

 pro])Osition that increased function of par- 

 ticular cells is reflected by increased volume 

 of their nuclei, cell nuclear volumes were 

 measured in hypothalamic nuclei of female 

 mice at different stages of the estrous cycle. 

 During proestrum and estrus there was 

 said to be a functional edema in hypothal- 

 amic nucleus 20 of Griinthal (possibly the 

 pars posterior of the ventromedial nucleus 

 of Krieg) and to lesser extent in nucleus 16 

 (Nucl. arcuatus). 



1. The Ilypophi/seal Portal Veins and the 

 Chemotransmitter Hypothesis 



As noted elsewhere, hypothalamic control 

 of the jiars distalis is probably mediated by 

 the hypophyseal portal circulation. Evi- 

 dence for this has been especially con- 

 vincing with respect to control of ovulation, 

 although indications are that other phases 

 of the cycle are also regulated by this 

 means. Pertinent data from numerous trans- 

 plantation and stalk-section experiments 

 may be summarized by the following state- 

 ment. Aside from a questionable grafting 

 experiment (2 rats) reported by May 

 (1937), in no case has ovulation or luteini- 

 zation been reported in the absence of vas- 

 cular linkage of the pars distalis with the 

 median eminence; on the other hand, ovu- 

 latory cycles have often been cjuickly re- 

 stored when the gland has been revascular- 

 ized by the portal vessels (see especially, 

 Harris, 1950a; Harris and Jacobsohn, 1952; 

 Nikitovitch-Winer and Everett, 1957, 

 1958b). 



Although the importance of local vasom- 

 otor regulation in the stalk vessels remains 

 to be evaluated (Green, 1951), there is ex- 

 tensive support for the hypothesis that ovu- 

 latory release of gonadotrophin is invoked 

 by a chemotransmitter (Harris, 1948a, 

 1955). If one accei)ts the prevailing opinion 

 that nerve fibers entering the pars distalis 

 are too few to account for its secretomotor 

 control and that the flow of blood in the 

 hyi^ophyseal portal vessels is toward the 

 gland (Wislocki and King, 1936; Green, 

 1947; Green and Harris, 1947, 1949; Barr- 

 nett and Greep, 1951 ; Landsmeer, 1951 ; 

 ]McConnell, 1953; Xuereb, Prichard and 

 Daniel, 1954; Worthington, 1955), the 

 plausibility of the chemotransmitter hy- 

 pothesis becomes inescapable.^ 



Evidence that the transmitter may l)e 



^ For a dissenting view, see Zuckerman (1952). 

 Reference should also be made to the hypothesis 

 formulated by Spatz (1951) and associates (see 

 Nowakowski, 1950, 1952). They postulated that 

 a descending pathway in the spinal cord is the 

 connecting link between hypothalamus and ova- 

 ries. With respect to ovulation, this is clearly 

 denied by the fact that local stimulation of the 

 hypotlialamus provokes ovulation in rabbits in 

 which the thoracic spinal cord has been trans- 

 sected (Christian, Markee and Markee, 1955). 



