The Role of the Pituitary Gonadotropins 1 9 



a few ova, reported here upon preparatory treatment by high unitages of 

 FSH and ICSH, was accompanied by excessive luteinization of the majority 

 of the follicles with enclosure of their ova. Sporadic instances of ovulation 

 without supplementary treatment have also been observed during routine 

 assay of gonadotropins, especially those of human pituitary origin, and here 

 again the answer may lie in the high proportion of ICSH present. Ovulation 

 in hypophysectomized rats after injection for four days of human pituitary 

 has been reported by Bahn et a/. (1) and by Velardo with sheep FSH and 

 ICSH (28). 



That the injection per se is not the stimulus has been shown by the inade- 

 quacy of lower doses of FSH, ICSH or HCG than those illustrated in the 

 tables. A common factor might be sought in the possible contamination of 

 all these products by minute amounts of substances such as posterior lobe 

 hormones.* The existence of a separate "ovulatory hormone" has also been 

 postulated (5). It is difficult, though not impossible, to conceive that another 

 factor of sufficient biological potency could accompany FSH and ICSH in 

 their present state of purification. 



SUMMARY AND CONCLUSIONS 



What has been learned thus far in experimental induction of ovulation in 

 rat and monkey may be summarized as follows. Ovulation has been induced 

 in normal immature and adult Macaca mulatta with sheep pituitary fractions 

 high in FSH, and by 40% ethanol extracts of monkey anterior pituitary, with 

 and without supplements of sheep ICSH or of HCG. Although the sheep 

 preparations which caused ovulation in the monkey were designated as "FSH" 

 and were prepared by methods which yielded potent FSH, which by physico- 

 chemical criteria consisted of homogeneous protein, they were nevertheless 

 not homogeneous biologically, and still contained small amounts of ICSH. 



These experiments were also subject to the criticism that normal recipients 

 were used and the pituitary undoubtedly contributed to the response. This 

 criticism has been obviated in the studies conducted in hypophysectomized 

 rats. Sheep FSH prepared similarly to that used in monkeys, as well as 

 further purified FSH preparations of greater potency, in which ICSH contami- 

 nation had been further reduced, have been examined carefully for their 

 adequacy in induction of ovulation in the hypophysectomized rat. FSH 

 preparations of potency comparable to those used in the monkey, with MED 

 25 jxg and containing 10% ICSH were effective both in promoting growth of 

 follicles and, terminally at higher doses, in giving the final impetus to 

 ovulation. FSH preparations of greater potency, MED 4 to 1.7 /xg, which 



* Subsequent experiments have indicated that neither Pitressin, in doses of 0.5 or 0.05 

 dog pressor units, nor Pitocin, in doses of 0.5 or 0.05 guinea-pig uterine units, is effective 

 as an ovulatory supplement after follicular development by the FSH preparation used in 

 establishing standard conditions for ovulation. (The two products were supplied by Parke, 

 Davis & Co.) 



