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Human Reproduction, Vol 12, 774-779, Copyright © 1997 by Oxford University Press

ARTICLES

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

A Hurwitz, Z Finci-Yeheskel, A Milwidsky, S Yagel, EY Adashi, N Laufer and M Mayer
Department of Obstetrics/Gynecology, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.

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.
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