088 



PHYSIOLOGY OF GONADS 



son and Evans, 1958 j. Administration of 

 vitamin C concomitant witli gonadotropliin 

 has been claimed to enhance ovarian re- 

 sponse (DiCio and Schteingart, 1942), but 

 in another study the addition of ascorbic 

 acid inhibited the hiteinizing and ovulating 

 action of the gonadotrophin (Desaive, 

 1956). 



Whether induced by vitamin deficiency 

 or by inanition, the anestrum in rats which 

 follows 2 to 3 weeks' feeding of a vitamin 

 B-deficient diet has been explored as a 

 method for the assay of gonadotrophin. 

 Pugsley (1957) has shown that there is 

 considerable convenience of method and a 

 satisfactory precision of response for the 

 assay of HCG and pregnant mare serum. 



2. Uterus and Vagina 



a. Inanition. Limited food intake does 

 not prevent an increase in uterine weight 

 after estrogen. Testosterone propionate will 

 markedly increase uterine growth despite 

 a 50 per cent reduction in food intake 

 (Leathem, Nocenti and Granitsas, 1956). 

 Furthermore, dietary manipulations involv- 

 ing caloric and protein levels did not pre- 

 vent the uteri of spayed rats from re- 

 sponding to estrogen (Vanderlinde and 

 Westerfield, 1950). More specific biochem- 

 ical and physiologic responses must be 

 measured because starvation for 4-day pe- 

 riods clearly interferes with deciduoma for- 

 mation (DeFeo and Rothchild, 1953). A 

 start in the direction of studying tissue- 

 composition changes has been made by 

 measuring glycogen. However, no changes 

 were noted in uterine glycogen in fasting 

 rats (Walaas, 1952), and estrogen promoted 

 glycogen deposition in the uteri of starved 

 rats as well as in the uteri of fully fed rats 

 (Bo and Atkinson, 1953). 



b. Fat. Interest in the hormone content of 

 fat from the tissues of animals treated with 

 estrogen for the purpose of increasing body 

 weight has raised the question of tissue hor- 

 mone content. If estrogen was to be de- 

 tected in tissues, an increase in dietary fat 

 was necessary. However, the increase in 

 dietary fat decreased the uterine response to 

 stilbcstrol (I'mberger and Gass, 1958), thus 

 complicating the assay. 



c. Vitainins. Stimulation of the uterus 

 by estrogen does not require tliianiinc, ribo- 



flavin, pyridoxine, or pantothenic acid. On 

 the other hand, a deficiency of nicotinic acid 

 appears to enhance the response to low 

 doses of estrogen (Kline and Dorfman, 

 1951a, b). However, Bio appears to be 

 needed for optimal oviduct response (Kline, 

 1955) and is required for methyl group syn- 

 thesis from various one-carbon precursors 

 including serine and glycine (Johnson, 

 1958). 



Response of the bird oviduct to stilbestrol 

 requires folic acid (Hertz, 1945, 1948). It 

 was shown subsequently that stilbestrol and 

 estrone effects in frogs, rats, and the rhesus 

 monkey also require folic acid. A folic acid 

 deficiency can be induced by feeding ami- 

 nopterin. In this way the estrogen effects 

 can be prevented. Aminopterin also prevents 

 the action of progesterone in deciduoma 

 formation, from which it may be inferred 

 that folic acid is necessary for deciduoma 

 formation in the rat. Increased steroid or 

 folic acid levels can reverse the antagonist's 

 effect (Velardo and Hisaw, 1953). 



The mechanism of folic acid action is not 

 clear. It may function in fundamental meta- 

 bolic reactions linked with nucleic acid 

 synthesis. Brown (1953) showed that 

 desoxyribonucleic acid could be substituted 

 for folic acid in the bird. In the rat ami- 

 nopterin interferes with the increase in 

 uterine nucleic acids, and with nitrogen 

 and P-^- uptake by nucleic acids following 

 estrogen. Folic acid has been implicated in 

 the metabolism of several amino acids 

 (Davis, Meyer and McShan, 1956). 



Rats ovariectomized at weaning and 

 maintained on a vitamin E-free diet for 

 6 weeks to 10 months responded to estradiol 

 in the same manner as rats supplemented 

 with tocopherol. This finding suggests that 

 an intimate physiologic relationship be- 

 tween estradiol and vitamin E is not very 

 probable (Kaunitz, Slanetz and Atkinson, 

 1949). Nevertheless, vitamin E has been 

 re]:»orted to act synergistically with ovarian 

 hormones in dc^ciduoma formation (Kehl, 

 Douard and Lanfranchi. 1951 ) and to in- 

 fluence nucleic acid turnover (Dinning. 

 Simc and Day, 1956). 



A vitamin-hormone interrelationship is 

 apparent when estrogen and vitamin A are 

 considered. Vitamin A-deficient female rats 

 present evidence of a metaplastic uterine 



