Pharmacology 191 



nortiiiit lo consider ulun one knows how olten the alkaloid has been 

 nsed lor the detection ot hormone-stimulated growth (Clhaj^ter 9) . 



Durini; the brecdino season, the fish Rhodeus itinanis displays 

 biilliant red "niijjtial colors," which are related to the expansion ol 

 chromatophores and to local hyperemia, 1 hese colors appear in 

 animals treated with male hormones. Colchicine alone has the same 

 effects. •^-- ■^•^ Nuptial colors are displayed bv fish subjected tor 10 

 minutes to a 1,5/1000 solution, or tor 35 minutes to a concentration of 

 0.75/1000, Colchicine and hormones add their effects, and the tidl 

 skin changes could l)c produced in 2 instead ot 20 hoins with hormone 

 alone. The oxygen consumption of the animals ^\■as also increased."'" 

 Howe\er. the "endocrine" mechanisms ot this action of colchicine may 

 be ciuestioned. In females of the same species, no increase in the size 

 of the o\ipositor was noted.'' The changes of the male fishes, where 

 \asomotor mechanisms play a great part, may have been either the 

 consecjuence of a nervous action, or of the general toxicity of colchicine. 



The possibility of stimulating the action ot ijituitary hormones ])y 

 the alkaloid was strongly suggested by experiments on the ovulation of 

 isolated ovaries of Rana pifjicns. This was considerably accelerated, 

 both in \\hole animals and on isolated ovaries (Fig. 7.S) . The eggs 

 were tcrtili/aljle, biu none e\er dixided. Colchicine was believed to 

 bring a "true j:)otentiation" of the pituitary hormones controlling 

 ovulation.'- In the rai)i)it, however, no jjotentiation of the action of 

 pregnant mare's serum, containing gonadotropic hormones, on the 

 rate of ovulation could be detected.'*- Colchicine had no action on the 

 weight of oxaries of mice similarly injected, or on the seminal vesicles 

 of rats injected with testosterone,"'- Neither do results of experiments 

 on silk-worms-^-' justify the conclusion that colchicine is "hormone- 

 mimetic," 1 he onh ]K)ssil)ilit\ is that through nonspecific action, 

 this toxic drug could stimulate the secretion of hormones b\ endocrine 

 glands, in ]:)articidar the j)ituitary. 



7.5-2; Liver and kidney damage. The mechanism ot these changes 

 is not clearly tmderstood, but it certainly plays an important part 

 in the general toxicity of the drug. I hough bile secretion has Ijcen 

 supposed to be increased, se\ere degenerative changes and necrosis 

 have been described in the livers of mice,""' especially after repeated 

 injections.^" In mice, the LD-,„ dose induces li\er cell steatosis in one 

 hour.''- Steatosis ot heart muscle cells and kidney tubules xvas also 

 noted. Female mice appear U) be more resistant to this damage than 

 males. 



Mitoses ot li\cr cells ha\e Ijeen described in hiinian poisoning bv col- 

 chicine. 1 here are often arrested metaphases. c\en long after the drug 

 has been administered, a fact xvhich is explained in its slow excretion.^' 

 Three days after injection ot colchicine in mice, normal mitoses also 



