Discussion 99 



of 2 to 5 ml of raw semen, or the sediment obtained by centrifuging raw semen and 

 preputial fluids containing large numbers of bacteria, into the uteri of heifers during 

 estrus also induced precocious heat. 



All of these treatments involving uterine insults also resulted in marked inhibition 

 of the development of the corpus luteum. In some cases cystic corpora lutea resulted ; 

 in others the corpora lutea were simply quite small. Relatively few normal functional 

 luteal cells were present in either case. 



The physiological role which oxytocin plays in the regulation of the estrous cycle in 

 cattle has not yet been established. It is conceivable that oxytocin injections, uterine 

 dilatation, and the infusion of materials containing large numbers of bacteria into the 

 uterus all cause luteal inhibition and precocious estrus by interfering with the normal 

 production of some luteotropic substance by the bovine endometrium during the 

 first half of the estrous cycle. Experiments now being carried out in which bovine 

 endometrial extracts are injected into normal and pseudopregnant rats should provide 

 an answer to this question. 



Uterine stimulation in the bovine causes oxytocin release (Hays, R. L. and N. L. Van 

 Demark, Endocrinology 52, 634-637, 1953) and it is tempting to assume that the 

 uterine dilatation and irritatioii in these experiments caused oxytocin release, which 

 in turn inhibited luteotropin secretion either directly, or indirectly by influencing the 

 hypothalamic release of some other neurohumor. The failure of oxytocin to induce 

 estrus in hysterectomized heifers argues against such an interpretation, but this 

 subject needs further study since the ovarian changes in these animals were not carefully 

 followed and since it has also been found that multiple ovulations can occur in the 

 ovaries of gonadotropin-treated, hysterectomized heifers in the absence of estrus. 



Although these experiments indicate that oxytocin injections inhibit luteotropin 

 secretion in the bovine, there are indications that exogenous oxytocin has the opposite 

 effect in the rat (Benson, C. K. and S. J. FoUey, J. Endocrinol. 16, 189, 1957; and 

 Desclin, L., Ann. Endocrinol. 17, 586, 1956). In some preliminary experiments (un- 

 published) we have produced deciduomata in 4 of 8 oxytocin-treated rats by passing 

 threads through their uteri 6 days after estrus and stimulation of the cervix, as compared 

 to of 6 rats treated in the same way but given no oxytocin injections. These results 

 again suggest a luteotropic response to injected oxytocin in the rat. 



Although it has not been possible to produce ovulation in the rabbit by oxytocin 

 injections or by continuous infusion of oxytocin into the carotid artery over a period 

 of 2 hours, there are some indications of increased gonadotropin secretion in the 

 rabbit as a result of oxytocin injections. Armstrong and Hansel {Internal. J. Fertil. 3, 

 296-306, 1958) have reported increased testis weights and seminiferous tubule 

 diameters, and increased interstitial cell development in immature rabbits injected 

 daily with oxytocin for 11 weeks. Martini et al. {J. Endocrinol. 18, 245, 1959) have 

 reported an increased urinary gonadotropin excretion in rabbits injected with oxytocin- 

 containing preparations. Preliminary results indicate that oxytocin injections have 

 no effect on estrous cycle length in normal ewes and guinea-pigs. 



One of the most perplexing problems related to this subject has been the apparent 

 lack of specific and repeatable effects of the various ovulation-blocking drugs. This 

 has perhaps been more obvious in our work with cattle than it has been in experiments 

 with other species. Atropine given at the beginning of estrus blocks ovulation in about 

 75% of the treated animals, but the blockage is temporary and ovulation usually 

 does occur a few days later and in the absence of a second estrus. Concurrent injections 

 of atropine or reserpine reduce the percentage of heifers that respond to daily oxytocin 

 injections by a precocious estrus, but some heifers do have shortened cycles. Results 

 such as these have been difficult to inteipret, and may even suggest that the blocking 

 drugs accomplish their effects in some non-specific manner such as by reducing 

 blood flow through the portal vessels. Worthington {Endocrinology 66, 19-31, 1960) 

 has recently reported a reduced blood flow in the portal vessels in the mouse after 

 injections of certain blocking drugs. 



The reports of Sawyer and Kawakami are of particular importance in that they 

 provide for the first time a common physiological effect of all the blocking drugs 



