The role of tyrosine kinase in gonadotropin-induced ovulation in the rat ovary.
OBJECTIVE
Our purpose was to elucidate the involvement of the tyrosine kinase pathway in gonadotropin-induced ovulation in the rat ovary.


METHODS
We investigated the effect of a tyrosine kinase inhibitor, tyrphostin, on the rat ovulatory process in vivo and in vitro.


METHODS
In cultured rat granulosa cells, the effect of tyrphostin on LH-, dibutyryl cyclic AMP ((Bu)2cAMP)- or forskolin-stimulated tissue type plasminogen activator (tPA) activities was examined by using a fibrin autography technique. In an in vivo system, tyrphostin was injected into the bursal cavity of the ovary in pregnant mare serum gonadotropin-treated rats, just before human chorionic gonadotropin administration. After 24 h, the number of oocytes in the oviduct was counted and the tyrphostin-treated ovaries were examined histologically.


RESULTS
Tyrphostin inhibited LH-stimulated tPA activity but did not affect (Bu)2cAMP- or forskolin-stimulated ones. In an in vivo study, tyrphostin suppressed oocyte release dose-dependently. Histological observations revealed that tyrphostin-treated ovaries contained many large unruptured follicles and a few corpora lutea.


CONCLUSIONS
This study suggests that the suppressive effect of tyrphostin on ovulation may be partly due to tPA activity inhibition in the granulosa cells via the suppression of tyrosine kinase activity. Additionally, tyrosine kinase phosphorylation may be involved in gonadotropin-activated signaling systems in the rat ovulatory process.
Shimamoto
T
T
Department of Obstetrics and Gynecology, Wakayama Medical College, Japan.
Yamoto
M
M
Nakano
R
R
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects; D007986:Luteinizing Hormone / Q000494:pharmacology*; D008845:Microinjections; D010062:Ovulation Induction / Q000379:methods*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D005576:Colforsin; D003994:Bucladesine; D007986:Luteinizing Hormone; D011505:Protein-Tyrosine Kinases; D010959:Tissue Plasminogen Activator