DISCUSSION 



Dr. Ernest Knobil: I would much prefer to stand in mute admiration of Dr. Simpson's 

 impressive studies, but since siie has mentioned some of our work dealing with ovulation 

 in the hypophyscctomized rhesus monkey, I will accept this opportunity to take the 

 floor. 



As Dr. Simpson indicated, we were able to induce ovulation in hypophyscctomized 

 monkeys by the subcutaneous administration of porcine FSH followed by the simul- 

 taneous administration of this FSH preparation and HCG (Etulocrinolugy 65, 487, 

 1959). We most certainly concur with Dr. Simpson that non-primate FSH preparations 

 are highly active in the monkey and that their administration, in small quantities, all 

 too easily leads to the production of cystic follicles. 



Our few attempts to induce ovulation in hypophyscctomized monkeys with LH 

 preparations other than HCG (non-primate pituitary LH) were uniformly unsuccessful. 

 These findings, the difficulties encountered by other workers in the induction of 

 ovulation in normal monkeys with non-primate pituitary LH preparations, coupled 

 with our experiences with the species specificity of growth hormone, prompted us to 

 determine whether a similar specificity could account for the apparent ineffectiveness 

 of non-primate LH preparations in primates. 



Because of the complexities in the ovulatory mechanism and other matters described 

 by Dr. Simpson we decided to test the effects of these LH preparations in the male 

 hypophyscctomized monkey rather than in the female. We estimated their stimulatory 

 effect on androgen secretion by the interstitial cells of Leydig by measuring the 

 secondary effects on the epithelium of the seminal vesicles and on the seminiferous 

 tubules of the testes. 



It was also felt that considerations of species specificity would be equally applicable 

 to both sexes. With the apologia for the interjection of the testis into an ovarian 

 conference I should like to summarize some of our experiments. 



Male monkeys which had been hypophyscctomized for 2 months to 3^ years were 

 used. Testicular and seminal vesicle biopsies were performed approximately two weeks 

 before the treatment period. The tissues were stained with hematoxylin and eosin. 

 In addition, frozen sections of a portion of the testicular biopsy material were prepared 

 and stained with Sudan black B. The various hormone preparations were administered 

 twice daily by subcutaneous injection in 1 ml of 12% gelatin. This regimen was 

 continued for 14 days in all instances. On the day following the last injection the 

 contralateral testis and seminal vesicle were biopsied and the tissues prepared as 

 before. The hormone preparations used with their daily doses were as follows: 

 HCG (500 Units), Equine LH-Armour (10 mg equivalent of Armour standard). 

 Ovine LH-NIH (10 mg equivalent of Armour standard), and a human pituitary 

 gonadotropin concentrate kindly provided by Dr. S. L. Steelman. The latter was given 

 at a dose of 10 mg per day but its relative potency has not been established. 



All of these treatments resulted, within a few days, in edema and pigmentation of 

 the scrotum as well as variable degrees of testicular descent. The biopsies revealed 

 distinct stimulation of the secretoi"y epithelium of the seminal vesicle and enlargement 

 of the seminiferous tubules. The equine and human preparations which contained 

 large quantities of FSH as determined by rat assay occasioned, in addition, marked 

 mitotic activity in the spermatogcnic elements of the tubules. 



Gonadotropin treatment, while producing but modest and inconsistent hypertrophy 

 and hyperplasia of Leydig cells, resulted in a most striking sudanophilia of the 

 interstitial tissue. Figures 8 and 9 illustrate the response of a hypophyscctomized 

 monkey to ovine LH. 



22 



