48 Discussions 



is highly active on oral administration (in fact it is the most active ovulation 

 inhibitor) but of quite low potency by injection; norethindronc is similarly 

 somewhat more active by mouth than by injection. It is interesting to note 

 that thus far the most consistent oral ovulation inhibitors in women are 

 these two compounds, whereas others (e.g. XLI and LIV) are by themselves 

 not very effective oral agents in women (12, 13). 



REFERENCES 



1. PiNCUS, G. and M. C. Chang, Acta Physiol. Latino-americana 3, 177, 1953. 



2. PiNCUs, G., Proc. 5th Internat. Conf. Planned Parenthood, p. 176, 1955. 



3. PiNCUS, G., M. C. Chang, M. X. Zarrow, E. S. E. Hafez and A. Merrill, Endo- 



crinology 59, 695, 1956. 



4. MiYAKE, T. and G. Pincus, Endocrinology 63, 816, 1958. 



5. Saunders, F. J. and R. L. Elton, in Endocrinology of Reproduction (Edited by C. W. 



Lloyd), p. 227. Academic Press, New York, 1959. 



6. JuNKMANN, K., Arch. Exptl. Pathol. Pharmakol. 223, 244, 1954. 



7. Hertz, R., W. Tullner and E. Raffelt, Endocrinology 54, 228, 1954. 



8. Rock, J., G. Pincus and C. R. Garcia, Science 124, 891, 1956. 



9. Rock, J., C. R. Garcia and G. Pincus, Recent Progress in Hormone Research 13, 



323, 1957. 



10. Garcia, C. R., G. Pincus and J. Rock, Am. J. Obstet. & Gynec. 75, 82, 1958. 



11. Saunders, F. J. and V. A. Drill, Ann. N.Y. Acad. Sci. 71, 516. 1958. 



12. Pincus, G., Vitamins and Hormones 17, 307, 1959. 



13. Rock, J. and C. R. Garcia (this volume). 



DISCUSSIONS 



Chairman: Dr. Roy O. Greep 



Dr. Frederick L. Hisaw: The experiments reported by Dr. Simpson on the induction of 

 ovulation in monkeys (Macaca mulatta) and rats deal with two mammalian species 

 that differ widely in sensitivity to exogenous pituitary gonadotropins, and particularly 

 in responsiveness to the luteinizing hormone (LH). An unfractionated pituitary 

 extract that contains both FSH and LH, when given subcutaneously to monkeys in 

 moderate doses, produces primary growth of follicles, most of which may be cystic and 

 show little or no luteinization of the granulosa. If, following follicular development, 

 the same preparation is injected intravenously, luteinization usually occurs and 

 occasionally a follicle may rupture, but when this happens it always involves a follicle 

 of approximately normal size that has not become cystic. In contrast with this, a 

 similar preparation invariably causes luteinization in rats when administered sub- 

 cutaneously in effective doses for a period longer than 3 or 4 days. 



Therefore, as Dr. Simpson has emphasized, an analysis of follicular development 

 and ovulation as induced by pituitary gonadotropins must depend in large measure 

 on the purity of FSH and LH preparations, the length of treatment, the relation of 

 the two hormones in the reactions, and the responsiveness of the experimental animal. 

 It seems that LH can be obtained free of FSH but it is disappointing that so far no 

 one has succeeded in isolating FSH in sufficient purity that it will not produce 

 luteinization when given in large doses. This, of course, could mean an incomplete 

 separation of the two hormones but the possibility should be considered that the 

 weak luteinizing action of purified FSH may be due to an amino-acid sequence held 

 in common with LH as has been found for the melanophore-stimulating hormone 

 (MSH) and adrenocorticotropin (ACTH). 



