title: Progesterone mediates decreases in uterine smooth muscle cell interleukin-1alpha by a mechanism involving decreased stability of IL-1alpha mRNA.
abstract: The regulation, by progesterone, of serotonin-induced interleukin-1alpha production was studied in primary cultures of rat uterine smooth muscle cells. Prior reports from this laboratory have demonstrated that these cells produce IL-1alpha and IL-1beta mRNAs in response to the hormonal action of serotonin. Results of the present study indicate that treatment of myometrial smooth muscle cells with medroxyprogesterone acetate (MPA) results in a marked decrease in IL-1alpha protein as measured by western blot analysis. These decreases occur even in the presence of maximally-inducing concentrations of serotonin. MPA-mediated changes in IL-1alpha protein are characterized by a rapid decline in IL-1alpha mRNA levels. This inhibition by medroxyprogesterone also occurs when cells are stimulated to produce IL-1alpha by PMA rather than serotonin. Thus, when cells are cultured in the presence of both inducer and inhibitor, the inhibitor, progesterone, clearly dominates in the control of IL-1alpha expression. This effect is concentration-dependent, can be mimicked by native progesterone or glucocorticoids, but is unaffected by estradiol. The ability of progestins to decrease IL-1alpha mRNA is blocked by both inhibitors of transcription and translation and by treatment with RU-486. Progesterone had no effect on chloramphenicol acetyl transferase (CAT) transcription from two different IL-1alpha promoter constructs, indicating that progesterone's action appears to be dependent on post-transcriptional rather than transcriptional regulation. Conversely, progesterone accelerated the normal rate of decay of IL-1alpha mRNA that occurs following the removal of serotonin from the cultures. These results suggest that progesterone decreases IL-1alpha levels by stimulating the production of an intracellular intermediate that decreases the stability of IL-1alpha mRNA.
authors.affiliation: Department of Biochemistry and Molecular Biology, Albany Medical College, New York 12208, USA.
authors.forename: L
authors.initials: L
authors.lastname: Lan
authors.forename: J M
authors.initials: JM
authors.lastname: Vinci
authors.forename: J A
authors.initials: JA
authors.lastname: Melendez
authors.forename: J J
authors.initials: JJ
authors.lastname: Jeffrey
authors.forename: B D
authors.initials: BD
authors.lastname: Wilcox
mesh_terms: D000818:Animals; D002455:Cell Division; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D007375:Interleukin-1 / Q000235:genetics*; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D009215:Myometrium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D049590:Postpartum Period; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000096:biosynthesis; D012701:Serotonin / Q000494:pharmacology; D014162:Transfection
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012701:Serotonin; D011374:Progesterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D015500:Chloramphenicol O-Acetyltransferase; D006854:Hydrocortisone