PHYSIOLOGY OF ANTERIOR HYPOPHYSIS 



255 



inject 100 times as much frog as mouse hy- 

 pophysis to obtain minimal stimulation of 

 the mouse ovary. 



7. General Considerations 



There are probably no generalizations 

 that can safely be drawn from the variety 

 of taxonomic relationships noted in regard 

 to the gonadotrophins ; but, as Zuckerman 

 aptly contends, "knowledge can advance 

 little if we do not generalize." Wide dis- 

 tribution throughout the Vertebrata is sug- 

 gested for each of the gonadotrophins. The 

 information concerning their ciualitative 

 variation that is revealed by cross-species 

 testing is of fundamental importance to 

 both biology and medicine. Peculiarly, there 

 is little and perhaps no qualitative variation 

 in the gonadotrophins from various species 

 of teleosts (Ihering, 1937; Kazanskii, 1940; 

 Dodd, 1955), but the number of species 

 studied is not a fair sample of the number 

 existent. The situation is different in the 

 amphibia. Here qualitative variation in the 

 gonadotrophins from different s])ecies is 

 much in evidence. Seemingly, some anurans 

 are capable of responding to gonadotrophins 

 from any class of vertebrate, whereas others 

 fail to respond even to gonadotrophins from 

 closely related amphibian species ; albeit the 

 amphibia appear to be far more sensitive to 

 amphibian gonadotrophins than to those 

 from any other class of vertebrates. The 

 reptiles, although little studied, appear to 

 respond sluggishly to nonreptilian gonado- 

 trophins. Birds, too, respond best to bird 

 gonadotrophins, yet in some respects are 

 exceedingly! sensitive to those from a wide 

 variety of mammals. Among the mammals 

 great variations in responsiveness are re- 

 vealed by every exchange of gonadotrophins 

 between their species. The variations, how- 

 ever, are mainly of quantitative rather than 

 of qualitative nature so far as is known. 



The differences in species responsiveness 

 pose difficult problems in the bioassay of 

 the gonadotrophins. It is obvious that the 

 potency units assigned to a gonadotrophin 

 preparation assayed in a foreign species 

 have no significance as to equivalent po- 

 tency when the same preparation is tested 

 in other species, even when adjustment is 

 made so that the dose per unit of body 



weight is the same. Moreover, an apparent 

 ineffectiveness in one species may not nec- 

 essarily mean that the gonadotrophin is 

 biologically inactive; Creaser and Gorb- 

 man (1939) state that ''the effectiveness of 

 a gonadotrophic hormone in a foreign spe- 

 cies tends to vary directly with the phylo- 

 genetic proximity of the donor and recipient 

 species." 



Recently, a marked qualitative species 

 variation was demonstrated in connection 

 with another pituitary hormone, somato- 

 trophin. Preparations of swine, ovine, or 

 bovine somatotrophin were markedly effec- 

 tive in rats and dogs but not in monkeys or 

 man (for literature, see Smith, Gaebler and 

 Long, 1955). IVIonkey somatotrophin, how- 

 ever, was effective in monkeys and also in 

 rats (Knobil and Greep, 1956). Similarly, 

 fish somatotrophin, which was active in fish, 

 was inactive in mammals, whereas ox prepa- 

 rations were active in fish as well as in some 

 mammals (Pickford, 1954; Wilhelmi, 1955). 



We have seen that the physiologic prop- 

 erties of a gonadotrophin are as much an 

 expression of the sensitivity of the substrate 

 on which the hormone acts as of the ex- 

 citations of the hormone itself. This being 

 the situation, the difficulties to be faced in 

 retracing the evolutionary history of the 

 gonadotropins are indeed formidable. How- 

 ever, by extending lines of study that have 

 been followed over the past 20 years, pieces 

 of this fascinating problem may in time be 

 fitted together. At this early departure in 

 the quest, the dictum credited to Medawar 

 to the effect that, "It is not the hormones 

 which evolve but the uses to which they are 

 put" seems grossly premature; but its value 

 in addressing thoughtful inquiry to the 

 matter may be considerable. Another lab- 

 oratory aphorism to the effect that hormones 

 can be tested down the ])hyletic scale but not 

 in the reverse order undoubtedly contains 

 an element of truth, but as a generalization 

 it would seem to be fraught with much haz- 

 ard. Along these same lines Witschi (1955), 

 noting the spread in effectiveness of mam- 

 malian LH — at least to the amphibia — re- 

 marked, "One definite conclusion derives 

 clearly ^ from the now available evidence; 

 namely, that induction of ovulation is a 

 much more general and more ancient func- 



