title: Interleukin-1 beta inhibits progesterone accumulation in rat corpora luteal cell cultures in a mechanism dissociated from its effects on nitric oxide and prostaglandin E accumulation.
abstract: The objective of this study was to examine the effect of interleukin-1 beta (IL-1) on progesterone (P) biosynthesis and the potential intermediary involvement of prostaglandin (PG) E and nitric oxide (NO) in P accumulation in PMSG/hCG-primed rat corpora luteal (CL) cell cultures. Exposure of primed CL cells to IL-1 (10 ng/ml) for 48 h resulted in a 65-86% reduction (P < 0.01) in P accumulation concurrent with a 2-3.4-fold increase in PGE content, a 70% increase in PGF2 alpha content and a 1.9-3.3-fold increase in nitrite generation. These effects were abolished by the IL-1 receptor antagonist, suggesting specific IL-1 receptor-mediated effects. Indomethacin, a cyclooxygenase inhibitor, abolished PGE and PGF2 alpha production and attenuated the basal (but not IL-1-stimulated) accumulation of P. N(G)-Nitro-L-arginine (NNLA), a competitive inhibitor of nitrite synthesis, slightly reduced basal P accumulation but had no effect on IL-1-induced suppression of P accumulation. NNLA reduced basal PGE accumulation and IL-1-stimulated PGE accumulation (55 and 61%, respectively). Transforming growth factor beta 1 (TGF-beta 1; 10 ng/ml) significantly attenuated the IL-1-stimulated PGE and NO production (61 and 42%, respectively), but did not affect the ability of IL-1 to suppress P accumulation. Thus, NO, PGF2 alpha and PGE are not obligatory intermediaries of IL-1-mediated suppression of P accumulation in rat CL, but are involved in basal P biosynthesis and NO seems to have a regulatory role in the biosynthesis of PGE. The present observations suggest a pleiotropic response of PMSG/hCG-primed CL cells to IL-1, characterized by an independent suppression of P accumulation and a concomitant increase in NO, PGF2 alpha and PGE generation. Since IL-1 attenuates P accumulation, these findings may imply a direct autocrine/paracrine function for IL-1 in the maintenance or the demise of rat CL.
authors.affiliation: Department of Obstetrics/Gynecology, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Hurwitz
authors.forename: Z
authors.initials: Z
authors.lastname: Finci-Yeheskel
authors.forename: S
authors.initials: S
authors.lastname: Yagel
authors.forename: S
authors.initials: S
authors.lastname: Shimonovitz
authors.forename: N
authors.initials: N
authors.lastname: Laufer
authors.forename: E Y
authors.initials: EY
authors.lastname: Adashi
authors.forename: M
authors.initials: M
authors.lastname: Mayer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003338:Corpus Luteum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015237:Dinoprost / Q000378:metabolism; D005260:Female; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D011374:Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012795:Sialoglycoproteins / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011458:Prostaglandins E; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D011374:Progesterone; D015237:Dinoprost