XI. riTAKMACOLOGY 57 



iiig" noted depression of bone phosphatase by this siilistance. On the other 

 hand, alkaline phosphatase of renal distal tubuli of rats was increased by 

 PABA and glycosuria was said to result. ^'^ The significance of these findings 

 is not clear. Sulfonamides in general were not antagonistic but exerted the 

 same effect as PABA. 



7. Endocrine System 

 a. Thyroid 



The MacKenzies''^ first noted that PABA caused enlarg(Miient of the 

 thyroid gland of rats, and this observation was confirmed almost simid- 

 taneously by Astwood.^" The substance likewise produced this effect in 

 mice and dogs.*^ In vitro studies by Franklin et al.^'- showed that PABA in a 

 concentration of 10~^ .1/ depressed the rate of conversion of inorganic iodide 

 to thyroxine and diiodotyrosine. Berman*^ studied the effect of PABA in 

 six human patients with thyrotoxicosis and obtained a good antithyroid 

 response in each case. Dosage was 1 to 1.5 g. parenterally six times weekly 

 for 3 to 9 months. 



Adult male rats fed large doses of PABA for 19 to 45 days" responded 

 with an increase in size of the th3a'oid gland from 17 mg. to 41 mg. and a 

 fall of oxygen consumption of 30%. However, the goiterogenic activity of 

 PABA was relatively weak.^* According to McGinty and Bywater,-''^ the 

 activity of PABA is 0.3, with thiouracil taken as 100. Vanderlaan and 

 BisselP^ also noted the goiterogenic action of PABA to be slight but defi- 

 nite. In large doses (2 g.) to human subjects, Gualco et al}' claimed anti- 

 thyroid activity of PABA to be nearly comparable to that of thiouracil and 

 methylthiouracil. PABA was found to resemble thiouracil in its action 

 rather than sulfaguanidine in that both its goiterogenic and hypeiplastic 

 actions were inhibited b}' iodide.** Both PABA and thiovu'acil inhibited the 

 in vitro formation of acetylthyroxine from acetyldiiodotyrosine.*^ 



*' P. H. Silver and J. S. R. Golding, Lancet I, 528 (1945). 



^'^ M. Koltay, K. KovAcs, M. Majoros, D. Halmdgyi, and K. Kelemeii. Orvosi Hclilnp. 



90, 382 (1949) [C. A. 43, 9245 (1949)]. 

 <3 C. G. .MacKonzie and J. B. MacKeuzie, EndocrinoUnjii 32, 185 (1943). 

 *» E. B. Astwood, ./. Fharmacol. Exptl. Therap. 78, 79 (1943). 

 ^' G. J. Martin, Arch. Hiochem. 3, 61 (1943). 



" A. L. Franklin, I. L. Chaikoff, and S. R. Lerner, ./. Biol. Chew. 153, 151 (1944). 

 " L. Berman, Proc. Sue. Expll. Biol Med. 59, 70 (1945). 



*^ K. A. Jensen and K. Kjerulf-.Iensen, Acta Pharmacol Toxicol. 1, 280 (1945). 

 " D. A. McGinty and W. G. Bywater, ./. Pharmacol. Exptl. Therap. 84, 342 (1945). 

 5s W. P. \'anderlaan and A. Bissell, Endocrinolony 38, 308 (1940). 

 " S. Gualfo and V. Patrono, Minerva med. 2. 353 (1917) \('. A. 42. 1657 (1948)]. 

 " C G. .MacKenzie, Endocrinologi/ 40, 137 1 1947 i. 

 " l^ Pitt-Rivers, Binchim. et Biophy.^. Arin 2. 311 d'.MSi \C. A. 43, 6298 (1949)]. 



