Fraenkel-Conrat, Li, and Simpson 189 



mized rats. Histological study of the ovaries of such doubly treated rats reveals 

 no indication of the presence of ICSH other than by its augmentation of the 

 follicle stimulating action of FSH. When ICSH is combined with higher doses 

 of FSH, however, it may lead to luteinization of the follicles. This phenome- 

 non led to its discovery and has prompted the name "luteinizing hormone 

 (LH)."^ Since sheep FSH alone will cause luteinization of follicles at suffi- 

 ciently high doses, it is difficult to decide whether the luteinizing action of 

 ICSH is a specific one or is due only to its FSH augmenting action previously 

 discussed.* In particular, after it was shown that similar augmentation and 

 luteinization effects could be produced on combining FSH with inorganic 

 salts or inert proteins, doubt was cast on the existence of this second gonado- 

 trophin, "LH." While it appears well established that FSH can be augmented 

 in its effect by nonspecific agents, the above described augmentation phe- 

 nomena of FSH produced by ICSH are most certainly due to a specific syner- 

 gism of the two substances, for the following reasons: (i) These effects can be 

 produced by injection at different sites of the body of the two gonadotrophins, 

 whereas nonspecific augmentation can be produced only by administration 

 of the mixture, and are most probably due to delayed absorption of the hor- 

 mone;^''" (2) less than i /xg. of ICSH augments the effect of a few microgiams 

 of FSH, whereas very large doses of nonspecific agents are needed to produce 

 stich augmenting effects; (3) heat inactivation of ICSH destroys also its capac- 

 ity to augment FSH. It may be hoped that as a result of the purification of 

 ICSH and with the recognition of its intrinsic effect on the interstitial tissue 

 (which is not given by salts and inert proteins), arguments against its existence 

 based on augmentation and luteinization phenomena will not be voiced any 

 longer. 



It has been mentioned that the ovarian weights produced by FSH (in normal 

 immature or hypophysectomized rats) rarely exceed 60 mg. after three days of 

 treatment; and that added ICSH augments these weights to no more than 

 double. By administering purified FSH and ICSH in the form of tannates, 

 however, ovaries ranging from 200 to 300 mg. can be produced under the same 

 conditions, similar to those produced with crude extracts. It thus appears 

 possible that the inert proteins in crude extracts may exert a nonspecific aug- 

 menting action which can be replaced by the use of tannic acid. 



Whereas augmentation of the effects of FSH by ICSH in females are well 

 recognized, augmentation of ICSH by FSH does not appear to occur; on the 

 contrary, marked follicular stimulation may mask the action of ICSH on the 

 interstitial tissue. 



In the male rat no clear evidence for synergism between purified FSH and 

 ICSH has been found.f Interesting parabiotic experiments are reported in the 



* Usually this luteinization of follicles obtained by combiniii;4 low or moderate levels of 

 FSH with ICSH is thecal luteinization in contrast to the granulosa lutcini/ation characteristic 

 of high levels of purified sheep FSH. 



t Nonspecific augmentation of the effect of ICSH on the \fnlial prostate of hypophysecto- 

 mized rats has been observed, using copper sulfate. 



