536 



PHYSIOLOGY OF GONADS 



usual length of time (Xikitovitch-Winer, 

 1957 j. In fact, there is reason to suspect 

 that even a transient impairment of circu- 

 lation in the median eminence-hypophj'seal 

 linkage can be a sufficient impetus to pseu- 

 dopregnancy. The experiments of Tauben- 

 haus and Soskin ( 1941 ) in which applica- 

 tion of an acetylcholine-prostigmine mixture 

 to the exposed hypophysis was followed by 

 pseudopregnancy, may well be explained 

 in some such way. 



It thus seems that in the rat tlie depriva- 

 tion of, or interference with, the normal con- 

 nection of the pars distalis with the median 

 eminence facilitates secretion of luteotro- 

 phin and at the same time eliminates luteo- 

 lytic mechanisms. It is significant that 

 transplants of pars distalis into the pituitary 

 capsule or to the immediate vicinity of the 

 median eminence resume cyclic function 

 (see page 512). The hypothalamus may 

 have an inhibitory effect on luteotrophic ac- 

 tivity of the pars distalis during the short 

 cycle in this species. Greep and Chester 

 Jones (1950) made the pertinent suggestion 

 in attempting to explain the induction of 

 pseudopregnancy by estrogen treatment, 

 that the fundamental action of estrogen 

 here is the suppression of FSH and LH, 

 after which luteotrophic secretion may 

 "proceed apace." 



There is necessarily some uncertainty 

 concerning the amount of luteotrophin se- 

 creted by the pars distalis when dissociated 

 from the brain. Three sets of facts indicate 

 that the output is larger than that in the 

 cycling animal. (1) Sufficient gestagen is 

 secreted by the engrafted animal to main- 

 tain a ])regnancy (Everett, 1956c; Meyer, 

 I'rasad and Cochrane, 1958) when the pi- 

 tuitary is trans])lanted on the day after 

 mating. (2) After stalk-transsection, in 

 which there is less initial destruction of 

 glandular parenchyma than in transplanta- 

 tion experiments, the corpora lutea enlarge 

 to a diameter like that usually found in late 

 pregnancy rather than remaining like those 

 of pseudopregnancy (Nikitovitch-Winer, 

 1957). (3) A single homotransplant of pars 

 distalis placed subcutaneously in an other- 

 wise normal female mouse will maintain a 

 se(iueiicc of pseudopregnancies that override 

 the short cycles expected of the animal's 

 own hypophysis (Miihlbock and Boot, 

 19591. This is also true of rats (Nikitovitch- 



Winer, uni)ublislie(l). To avoid the conclu- 

 sion that in such preparations the grafted 

 gland is secreting luteotrophin at an in- 

 creased rate, one must assume that the out- 

 l)ut of this hormone from the intact gland 

 is only slightly below threshold and that the 

 graft adds just enough to make the total 

 output effective. To explain the maintenance 

 of pregnancy one might assume that the 

 luteotrophin output and the resulting gesta- 

 gen secretion are no greater than during the 

 normal short cycle and that the formation 

 of deciduomas takes place because of the 

 deficiency of estrogen. The results of stalk- 

 section, however, cannot easily be explained 

 away. The weight of evidence, then, is in 

 favor of increased luteotrophin secretion by 

 hypophyses isolated from the brain by 

 severance of the stalk or transplantation. 



Under certain experimental conditions it 

 has seemed that to establish pseudopreg- 

 nancy all that is necessary is to block out 

 the forthcoming estrus and ovulation. Thus, 

 in cycling rats, when the hypophysis is 

 transplanted to the kidney as late as 60 

 hours after ovulation, the current diestrum 

 transforms into a permanent pseudopreg- 

 nancy supported by the existing set of cor- 

 pora lutea (Nikitovitch-Winer and Everett, 

 1958a ». Similarly, injections of chlorproma- 

 zine (Barraclough, 1957) or Pathilon 

 (ditsch and Everett, 1958) begun during 

 diestrum, may transform it into a pseudo- 

 pregnancy by blocking out the expected 

 estrus. 



The Miihlhock-Boot experiment men- 

 tioned above furnishes an instructive model 

 of the standard mammalian cycle, in which 

 both ovulation and pseudopregnancy are 

 spontaneous events. Given the extra pitui- 

 tary tissue producing luteotrophin at a pre- 

 sumably constant rate, with the output of 

 the normal ghmd fluctuating (juantitatively 

 and (jualitatively, the mouse or rat under- 

 goes one ])seudopregnancy after another. 

 Possibly, in animals that normally liave a 

 spontaneou.- hiteal phase, thei'c is a con- 

 sidei'ahle poUion ot' the pars distalis which 

 I'unctions somewhat indepeiidentl}- of the 

 hyputhalaiiius. with a continuous output of 

 luteotrophin as from the grafted gland in 

 the Mvihlb()ck-P)Oot pi-epaiation. The por- 

 tion nioic (Hrectly under control of the 

 me(lian eminence I zona tuberaHs'.'l would 



