PHYSIOLOGY OF ANTERIOR HYPOPHYSIS 



261 



tion. There is agreement that in man the 

 pituitary gonadotrophic jiotency falls dur- 

 ing the second month of gestation and re- 

 mains barely detectable until a few days 

 postpartum (Bruner, 1951). It has been 

 assumed that in man placental gonado- 

 trophin (HCG) is an important sustaining 

 factor. The pregnant mare, however, also 

 has a rich extrapituitary supply of gonado- 

 trophin, yet shows no decline in pituitary 

 gonadotrophic potency (Hellbaum, 1935). 

 Some have tried to relate the instances of 

 reduced pituitary potency during gestation 

 to high titers of circulating estrogens, but 

 the inconsistencies are again extreme. (For 

 reviews of this controversial literature see 

 Burrows, 1949; Ladman and Runner, 1953; 

 Cowie and Folley, 1955). Recent reports 

 have been few. Ladman and Runner (1953) 

 in a detailed study of the pituitaries of 

 l)regnant mice found changes suggestive of 

 a cyclic fluctuation in potency during gesta- 

 tion. In breeding mule deer the peak potency 

 occurred in the fall and was followed by a 

 sharp decline which persisted during most of 

 gestation with a slow rise occurring near 

 term (May or June). 



C. EFFECT OF DIETARY RESTRICTIONS ON 



PITUITARY GONADOTROPHIC POTENCY 



AND FUNCTION 



1. Underfeeding 



There is a large bodj' of experimental 

 data showing that poor nutritional status 

 whether caused by reduced food intake or 

 impaired assii^iilation has a deleterious in- 

 fluence on reproductive functions (for com- 

 IH-ehengive review of nutrition-endocrine 

 relationships, see Ershoff, 1952 and chapter 

 l)y Leathem). It has long been known that 

 in the common laboratory animals con- 

 trolled inanition and starvation produce 

 atrophy of the gonads and accessory sex 

 structures and varying degrees of infertility. 

 Similarly, loss of reproductive functions 

 have been observed in human populations 

 during periods of restricted food intake. 

 That the level of circulating gonadotrophins 

 is reduced under these conditions is indi- 

 cated by involution of the gonads and also, 

 as shown in rats, by the fact that the 

 gonads remain sensitive to administered 

 gonadotrophins (Werner, 1939), the excep- 



tion being that stimulation of the testis 

 requires an adequate replacement of vita- 

 min E. Since it has been found that the 

 pituitary gonadotrophin content remains 

 at normal (Maddock and Heller, 1947) or 

 somewhat greater than normal levels (^lei- 

 tes and Reed, 1949; Rinaldini, 1949) during 

 chronic caloric restriction, it would seem 

 that the primary defect in pituitary func- 

 tion is failure, not so much in the synthesis, 

 as the release of hypophyseal gonadotroph- 

 ins. Aladdock and Heller (1947) also em- 

 phasized the dichotomy that is evoked 

 through inanition between pituitary gonado- 

 trophic content (normal) and gonado- 

 trophic function ( low ) . This involves the 

 important assumption that the gonadal tis- 

 sues have not lost their sensitivity to gon- 

 adotrophic stimuli as a result of undernour- 

 ishment. That exogenous gonadotrophins are 

 effective under these circumstances does not 

 exclude the possibility of a relative reduc- 

 tion in substrate sensitivity. It is of interest 

 that castration type cells do not develop in 

 the pars distalis during inanition despite the 

 severe reduction in gonadal functions. That 

 pituitary potency does not increase pari 

 passu with inhibition of release of gonado- 

 trophin is an indication that production of 

 gonadotrophins is also impaired during these 

 periods of restricted food intake. 



a. Related observations on inanition and 

 sex function in man. Many times in the his- 

 tory of man he has been exposed to malnu- 

 trition of considerable duration. Currently, 

 two-thirds of the world's population is 

 undernourished and many authors incline to 

 the view that actual starvation will become 

 more widespread in the future. Although the 

 associated endocrine disturbances have been 

 given little attention in these conditions, 

 there is convincing evidence that they con- 

 stitute an extremely important part of the 

 syndrome. Among the clinical manifesta- 

 tions of chronic underfeeding, there are gen- 

 erally symptoms attributable to dysfunction 

 of the thyroid, adrenals, gonads, and pitui- 

 tary. The few laboratory experiments in 

 human starvation have not made full use of 

 the various indices of endocrine function. 

 Moreover, there is much doubt that studies 

 of the nature of the Minnesota Experiment 

 (Keys, Brozec, Henschel, Michelson and 

 Tavlor, 1950) conducted under situations 



