In-vitro modulation of plasminogen activator activity, prostaglandin E and nitric oxide production by interleukin-1 in pregnant mare serum gonadotrophin-primed theca-interstitial cells.
To examine the participation of the theca-interstitial (TI) compartment in cytokine modulation of ovarian function, the effects of interleukin-1beta (IL-1) on plasminogen activator (PA) activity and on prostaglandin E (PGE) and nitric oxide (NO) production were examined in cultures of pregnant mare serum gonadotrophin (PMSG)-primed rat TI cells. Exposure to IL-1 (10 ng/ml) resulted in a 25% reduction (P < 0.001) in PA activity, concurrent with a 4.6-fold increase in the ability of the corresponding conditioned media to inhibit exogenous urokinase activity. IL-1 also produced a 4.7-fold increase in PGE content and a 2.8-fold increase in NO generation. These effects of IL-1 were abolished by the IL-1 receptor antagonist, suggesting specific IL-1 receptor-mediated effects. Transforming growth factor (TGF)-beta1 (10 ng/ml) significantly attenuated the IL-1-stimulated PGE production and NO generation but did not affect the ability of IL-1 to suppress PA activity and stimulate urokinase inhibitor production. The NO synthase inhibitor N-nitro-L-arginine attenuated the IL-1-induced NO generation but had no effect on PA activity or PGE production. Thus, NO is not an obligatory mediator of IL-1 effects on plasminogen activation and PGE generation in rat ovary. The present observations attest to a pleiotropic response of PMSG-primed TI cells to IL-1, and suggest a paracrine/autocrine function for the TI compartment in ovulation and corpus luteum formation.
Hurwitz
A
A
Department of Obstetrics/Gynecology, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
Finci-Yeheskel
Z
Z
Milwidsky
A
A
Yagel
S
S
Adashi
E Y
EY
Laufer
N
N
Mayer
M
M
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D006064:Gonadotropins, Equine / Q000494:pharmacology*; D007375:Interleukin-1 / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism*; D011458:Prostaglandins E / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013799:Theca Cells / Q000187:drug effects*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D006064:Gonadotropins, Equine; D007375:Interleukin-1; D017395:Plasminogen Activator Inhibitor 1; D011458:Prostaglandins E; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator