G74 



PHYSIOLOGY OF GONADS 



1948) , vitamin B complex deficiency (Segal- 

 off and Segaloff, 1944; Biskind, 1946), and 

 protein restriction (Jailer and Seaman, 

 1950) all influence the capacity of the liver 

 to detoxify steroids. Reduced protein intake 

 is a primary factor in decreasing the effec- 

 tiveness of the steroid-inactivating system 

 (Jailer and Seaman, 1950; Vanderlinde and 

 Westerfield, 1950). Rats fed an 8 per cent 

 casein diet lose their capacity to inactivate 

 estrone within 10 days. However, ascorbic 

 acid alone or in combination with gluta- 

 thione restored the estrone-inactivating sys- 

 tem (Vasington, Parker, Headley and Van- 

 derlinde, 1958). 



Failure of steroids to be inactivated will 

 influence the hypophyseal-gonadal axis. In 

 turn the excess of estrogen will decrease 

 gonadotrophin production by the hypoph- 

 ysis and thus reduce steroid production by 

 the gonad. In addition nutritional modi- 

 fications influence hypophyseal and possibly 

 gonadal secretory capacity directly. Con- 

 ceivably, nutritional alterations could 

 modify the amount of steroid secreted or 

 interfere with complete steroid synthesis 

 by a gland. 



Fatty infiltration of the liver and a 

 general increase in fat deposition occur in 

 fed and fasted rats after the injection of 

 certain pituitary extracts and adrenal ster- 

 oids and after the feeding of specific diets. 

 Impaired estrogen inactivation has been 

 associated with a fatty liver, but Szego and 

 Barnes (1943) believe that the major in- 

 fluence is inanition. In fact, estrogens, es- 

 pecially ethinyl estradiol, interfere with 

 fatty infiltration of the liver induced by a 

 low protein diet (Gyorgy, Rose and Ship- 

 ley, 1947) or by a choline-deficient diet 

 (Emerson, Zamecnik and Nathanson, 1951). 

 Stilbestrol, however, did not prevent the in- 

 crease in liver fat induced by a protein-free 

 diet (Glasser, 1957). Estrogens that are 

 effective in preventing fatty infiltration may 

 act by sparing methionine or choline or by 

 inhibiting growth hormone (Flagge, Mar- 

 asso and Zimmerman, 1958). 



Ethionino, the antimetabolite of nu'- 

 thioniiK', Avill induce a fatty liver and in- 

 hibit hepatic protein synthesis in female, 

 but not in male rats (Farber and Segaloff, 

 1955; Farber and Corban, 1958). Pretreat- 

 ment of females with testosterone prevents 



the ethionine effect, but this blockage of 

 ethionine action need not be related to 

 androgenic or progestational properties of 

 steroids (Ranney and Drill, 1957). 



III. Hypophysis and Diet 



Studies involving acute and chronic star- 

 vation have shown that gonadal hypofunc- 

 tion during inanition is primarily due to 

 diminished levels of circulating gonado- 

 trophins. Because of the similarity to 

 changes following hypophysectomy, the 

 endocrine response to inanition has been 

 referred to as "pseudohypophysectomy." 



A. INANITION 



The hypophysis has been implicated in 

 human reproduction disturbances asso- 

 ciated with undernutrition. Hypophyseal 

 atrophy and a decrease in urinary gonado- 

 trophins have been observed in chronic 

 malnutrition (Klinefelter, Albright and 

 Griswold, 1943; Zubiran and Gomez-]\Iont, 

 1953) and anorexia nervosa (Perloff, 

 Lasche, Nodine, Schneeberg and Vieillard, 

 1954). Refeeding has restored urinary 

 gonadotrophin levels in some cases, but 

 hypoj^hyseal damage may result from severe 

 food restriction at puberty (VoUmer, 1943; 

 Samuels, 1948). 



The influence of inanition on the re- 

 productive organs of lal)oratory rodents 

 is well recognized but the cft'ects on the 

 hypophysis cannot be presented conclu- 

 sively. In support of prior investigations, 

 Mulinos and Pomerantz (1941a, b) in rats 

 and Giroud and Desclaux (1945) in guinea 

 pigs observed a hypophyseal atrophy fol- 

 lowing chronic underfeeding as well as a 

 decrease in cell numbers and mitoses. In 

 fact, refeeding after chronic starvation 

 resulted in only a partial recovery of hy- 

 pophyseal weight (Quimby, 1948). Never- 

 theless, complete starvation did not in- 

 fluence relative gland weight in female rats 

 (Meites and Reed, 1949), and cytologic 

 evidence (periodic acid-Schiff (PAS) test) 

 of an estimated 3- fold increase in gonado- 

 ti'ophin content was claimed following 

 chronic starvation (Pearse and Rinaldini, 

 1950). Assays of hypophyseal gonado- 

 trophin content in chronically starved rats 

 of both sexes have l)een reported as de- 

 creased (Mason and Wolfe, 1930; Werner, 



