The kinin system and ovulation in mammals

In this thesis I investigated the possibility that the kinin system could be involved in the process of ovulation. This study was divided into four parts, these are outlined be 1ow. (1) To determine whether and when the kinin system is activated in relation to ovulation, plasma kininogen levels were estimated in female rats, guinea pigs, and humans at different stages of their estrus or menstrual cycles. Non-ovulating females (women using oral contraceptives,, or post-menopausal women) and male guinea pigs served as controls. The ovulating females of all three species showed a marked decline in kininogen levels shortly before ovulation, suggesting that the kinin system was activated at this time. The fall was absent in the non-ovulating controls, with the exception of women using oral contraceptives. In the latter subjects the fall occurred at a similar time in the 'cycle', and was of a similar magnitude as the fall in normal women. These results showed that the fall is a preovulatory change and raised the possibility that a mechanism more fundamental than the events obstructed by the oral contraceptives could be at least partially responsible for the decline. (2) After establishing the timing of the fall in plasma kininogen levels, an attempt was made to locate the enzymes responsible for the change. The kinin-forming enzymes of the two locations most likely to be involved in kinin release during ovulation, that is, the plasma and the ovary were examined. The evidence indicated that kinin-forming enzymes were present in both locations and suggested that their concentrations increased as ovulation neared. (3) In order to examine the possibility that an ovulatory stimulus can activate the kinin system, female rats were treated with an ovulatory dose of luteinizing hormone (LH) or estradiol -17β one day before the anticipated time of ovulation and kininogen level declines. Estimation of plasma kininogen levels revealed marked declines in the LH-treated animals, estradiol-17β had no observable effect. This evidence suggested that LH, but not estradiol-17β could be responsible, at least in part, for the decreased kininogen values just before ovulation. (4) Lastly, to establish the ability of a kinin to initiate some of the more important events of the ovulatory process, the effects of bradykinin on ovarian smooth muscle contractility and ovarian follicular blood vessel permeability in the rat were examined. Bradykinin stimulated ovarian contractility in in vitro preparations to a significantly greater degree in ovaries isolated during the ovulatory period than at any other stage of the cycle. Also, the degree of movement of the dye Trypan Blue from the general circulation throughout ovarian follicular tissue over a ten minute exposure period was significantly greater in tissue from animals treated with bradykinin than those that were not. This suggests that bradykinin can increase ovarian follicular blood vessel permeability in the rat. Both of these bradykinin-induced effects were reduced, but not eliminated by indomethacin, suggesting that prostaglandins may be involved. Results from this study indicate that the kinin system is activated during the preovulatory period, possibly at the level of the ovary, that LH may be partially responsible for this activation, and that kinins may play a role in triggering increases in ovarian contractility and blood vessel permeability both directly and possibly via the release of prostaglandins. More definite proof awaits the development of a satisfactory kinin antagonist.Science, Faculty ofZoology, Department ofGraduat