i88 Pituitary Gonadotrophins 



from that of ICSH in being more pronounced upon subcutaneous than intra- 

 peritoneal administration. Furthermore, it has been shown that purified FSH 

 upon intraperitoneal administration antagonizes other gonadotrophins (even 

 subcutaneously administered FSH). Such antagonistic phenomena can be 

 produced with ecpial or even smaller amounts of FSH than are needed of 

 ICSH. It thus appears unlikely that such antagonism is due to contamination 

 with ICSH; antagonism probably is an inherent property of each gonado- 

 trophin.^^ 



These findings suggest the possibility that a limited degree of ICSH-like 

 properties may be characteristic of sheep FSH. This could be proven only by 

 isolation of physicochemically homogeneous FSH still showing these diverse 

 activities. Such relationships between hormones have been shown to exist in 

 the case of the adrenal steroids, several of which may combine high activity 

 in one respect with low activity in another direction, in which another hor- 

 mone of a slightly different structure may be highly active. Furthermore, the 

 gonadotrophin from pregnant mares appears to be a single protein while 

 showing both FSH and ICSH properties.^ 



In hypophysectomized rats FSH causes increases in testis weights, which 

 are more pronounced than those produced by similar amounts of ICSH. His- 

 tological examination indicates stimulation of the tubular development, 

 although it appears that spermatogenesis can be furthered much more effec- 

 tively if FSH is combined with ICSH. Testosterone alone has been shown to 

 be effective in both maintaining and repairing testicular function of hypophy- 

 sectomized rats; the gametrotropic effect of FSH is difficult to explain on the 

 basis of ICSH contamination and concomitant testosterone production, in 

 view of the atrophic condition of the accessories of rats treated with effective 



levels of FSH. 



Synergism 



It has been recognized for a long time that ICSH shows pronounced activity 

 in augmenting and modifying the action of FSH when both are given sub- 

 cutaneously. A reinvestigation of these synergistic effects, using purified hor- 

 mones, has led to the following conclusions: In female rats, immature normal 

 or hypophysectomized, subcutaneously injected ICSH augments the effects of 

 FSH on the ovaries and in particular the secondary effects on the uterus.^' ^^ 

 Ovarian-weight augmentation rarely exceeds loo per cent, in contradistinction 

 to that produced by combined administration of FSH with "secreted" inter- 

 stitial-cell-stimulating substances, such as the pregnancy urine principle. On 

 the other hand, uterine "augmentation" becomes quite pronounced when less 

 than 5 units of sheep FSH (alone insufficient to effect estrogen secretion) is 

 combined with about i unit of ICSH. This is all the more surprising since 5 

 units of ICSH would be needed to produce any effect on the interstitial tissue 

 in the same rats upon subcutaneous administration. Actually, under favorable 

 conditions, as little as one-fifth to one-tenth of a unit of ICSH may be detected 

 by its synergistic effect with 3-5 units of FSH on the uterus of hypophysecto- 



