ABSTRACT
OBJECTIVE: To test the hypothesis that inhibition of protein kinase (PK) activity or proteolysis inhibits ovulation. DESIGN: Rats were injected intrabursally with protein kinase (H9 or staurosporin) or proteinase (alpha 2-macroglobulin) inhibitors and oocyte release was evaluated. SETTING: Clinical Research Laboratory, Center for Reproductive Medicine, University of Kentucky Medical Center. PARTICIPANTS: Immature rats stimulated with pregnant mare serum gonadotropin. INTERVENTIONS: Staurosporin (1 or 10 microM), H9 (1 mM), alpha 2-macroglobulin (835 microIU of activity); or vehicle was injected into the right ovarian bursa. The left ovarian bursa remained intact. Animals immediately received human chorionic gonadotropin (hCG). MAIN OUTCOME MEASURES: Analysis of oocyte release and ovarian morphology. RESULTS: Oocyte release from the inhibitor-treated side decreased for the H9 group (8.1 +/- 1.9 fewer oocytes released, P less than 0.001) and the 10 microM staurosporin group (5.5 +/- 0.6, P less than 0.001). No change in oocyte release was observed in the 1 microM staurosporin, alpha 2-macroglobulin, or vehicle injected groups. Histologic examination of vehicle treated ovaries demonstrated numerous developing corpora lutea (CL; 20.5 +/- 2.1 CL/ovary) and a lack of preovulatory follicles. In contrast, ovaries treated with PK inhibitors contained unruptured preovulatory follicles coincident with fewer forming CL (11.5 +/- 3.5 CL/ovary). CONCLUSIONS: Inhibition of PK activity in vivo suppresses ovulation, demonstrating that protein phosphorylation plays an important intermediary role in the ovulatory process.
Subject(s)
Oocytes/drug effects , Ovulation/drug effects , Protease Inhibitors/pharmacology , Protein Kinase Inhibitors , Sulfonamides , Alkaloids/administration & dosage , Alkaloids/pharmacology , Animals , Chorionic Gonadotropin/pharmacology , Female , Isoquinolines/administration & dosage , Isoquinolines/pharmacology , Oocytes/cytology , Oocytes/physiology , Ovary/drug effects , Ovary/physiology , Protease Inhibitors/administration & dosage , Rats , Rats, Inbred Strains , Staurosporine , alpha-Macroglobulins/administration & dosage , alpha-Macroglobulins/pharmacologyABSTRACT
Uncontrollable hemorrhage can occur during any surgical procedure, and only an organized approach to its control will minimize morbidity and mortality. When routine hemostatic measures fail, extraordinary methods must be used. The use of intraabdominal packs with a MAST (medical antishock trousers) suit successfully controlled a life-threatening hemorrhage in one such patient.
