196 PTEROYLGLUTAMIC ACID 



periods of 43 to 60 days until typical signs of PGA deficiency developed. 

 They were then given 66 y of estradiol benzoate. Six of the eight deficient 

 monkeys failed to show the characteristic normal estrogenic response in 

 the external genitalia. Simultaneous administration of a liver extract con- 

 taining PGA permitted the normal response to estrogen although pure 

 PGA was not employed in this experiment. A similar relationship exists in 

 the estradiol-treated ovariectomized rat.^^^ The weight of the uterus of the 

 untreated ovariectomized rat was found to be 25 mg., which was increased 

 to 84 mg. by injection with estradiol. In the presence of 12.5 y of the an- 

 tagonist 4-amino PGA, the uterine weight was 32 mg. after estradiol injec- 

 tion. The effect of 12.5 y of antagonist in decreasing the response to es- 

 tradiol was reversed by PGA. Corresponding results have been observed 

 in frogs. Goldsmith et al}^^ showed that the oviducts of newly metamor- 

 phased frogs exhibited a marked response to weekly injections of 0.1 mg. 

 of estradiol benzoate. Administration of PGA increased the response, 

 whereas 4-amino PGA decreased it. The effect of 4-amino PGA was not 

 negated by simultaneous administration of PGA. 



Evidence regarding the role of PGA in endocrine responses have not 

 been as clearly defined in the male as they have in the female. Goldsmith 

 et al}^^ measured the increase in weight of the seminal vesicles and coagu- 

 lating glands of testosterone-treated mice. Ten per cent of crude "x methyl 

 PGA" in the diet prevented the effect of testosterone, but 6 % did not. 

 Thus a higher level of antagonist is necessary to prevent the testosterone 

 effect in mice than is required to inhibit the action of stilbestrol in 

 chicks. ^°^' ^"^ In the rat 4-amino PGA did not interfere with stimulation of 

 the prostate by testosterone in either the intact immature rat or in the 

 castrate animal (Brendler"^). It was also observed that 4-amino PGA did 

 prevent the depressing effect of a-estradiol on the prostate in the intact 

 adult animal. Thus this PGA antagonist interferes with the tissue response 

 to estradiol, whether it be the growth stimulation of the oviduct or uterus 

 in the female, or the depressing effect of estradiol on the prostate in the 

 male. 



No effect of PGA has thus far been observed on the increased comb 

 growth produced by androgen in the chick. Haque et al}"^^ found that defi- 

 ciency of PGA, pantothenic acid, nicotinic acid, choline, or vitamin A had 

 no effect on the increase in comb growth produced by testosterone pro- 



112 R. Hertz and W. W. Tullner, Endocrinology 44, 278 (1949). 



113 E. D. Goldsmith, S. S. Schreiber, and R. F. Nigrelli, Proc. Soc. Exptl. Biol. Med. 

 69, 299 (1948). 



11^ E. D. Goldsmith, H. M. Black, and R. F. Nigrelli, Natvre 164, 62 (1949). 

 ii"* H. Brendler, Science 110, 119 (1949). 



ii« M. E. Haciue, R. J. Lillie, C. S. Shaflner, and G. M. Briggs, Foiiltri/ Scie?ice 28, 914 

 (1949). 



