Intrabursal administration of protein kinase or proteinase inhibitors: effects on ovulation in the rat.
OBJECTIVE
To test the hypothesis that inhibition of protein kinase (PK) activity or proteolysis inhibits ovulation.


METHODS
Rats were injected intrabursally with protein kinase (H9 or staurosporin) or proteinase (alpha 2-macroglobulin) inhibitors and oocyte release was evaluated.


METHODS
Clinical Research Laboratory, Center for Reproductive Medicine, University of Kentucky Medical Center.


METHODS
Immature rats stimulated with pregnant mare serum gonadotropin.


METHODS
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).


METHODS
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.
Guerre
E F
EF
Department of Obstetrics and Gynecology, University of Kentucky, Lexington 40536.
Clark
M R
MR
Muse
K N
KN
Curry
T E
TE
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005260:Female; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010053:Ovary / Q000187:drug effects / Q000502:physiology; D010060:Ovulation / Q000187:drug effects*; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D013449:Sulfonamides; D000511:alpha-Macroglobulins / Q000008:administration & dosage / Q000494:pharmacology
D000470:Alkaloids; D006063:Chorionic Gonadotropin; D007546:Isoquinolines; D011480:Protease Inhibitors; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000511:alpha-Macroglobulins; C044388:N-(2-aminoethyl)-5-isoquinolinesulfonamide; D019311:Staurosporine