Prostaglandin F2alpha stimulates 11Beta-hydroxysteroid dehydrogenase 1 enzyme bioactivity and protein expression in bovine endometrial stromal cells.
11Beta-hydroxysteroid dehydrogenase (HSD11B) enzymes have important roles in regulating cortisol availability in target tissues. We previously demonstrated that HSD11B1 is expressed and active in bovine endometrium and that cortisol suppresses prostaglandin (PG) F2alpha and PGE2 production in cultured bovine endometrial stromal cells. The present study was conducted to examine whether locally synthesized PGF2alpha and/or PGE2 regulates the enzymatic bioactivity and/or the expression of HSD11B1 in bovine endometrium. The conversion rate of cortisone to cortisol in cultured endometrial stromal cells was significantly stimulated by PGF2alpha (1 and 10 microM). In a dose-dependent manner, PGF2alpha but not PGE2 increased the net conversion of cortisone to cortisol in stromal cells after 4 h of treatment. In addition, the bioactivity of HSD11B1 was significantly inhibited by indomethacin (10 microM). The inhibitory effect of indomethacin on HSD11B1 bioactivity was abolished by PGF2alpha (1 microM) but not by PGE2. Although PGF2alpha (1 microM) did not affect the expression of HSD11B1 mRNA in cultured stromal cells, it significantly stimulated the protein expression of HSD11B1. Cycloheximide, a general translational inhibitor, abolished the stimulatory effects of PGF2alpha on HSD11B1 protein expression in endometrial stromal cells, indicating that PGF2alpha increases HSD11B1 protein expression by stimulating a posttranscriptional process rather than a transcriptional mechanism. These results demonstrate that PGF2alpha but not PGE2 increases HSD11B1 bioactivity and protein expression by stimulating a posttranscriptional mechanism in stromal cells and suggest that cortisol has a physiologically relevant role in preventing excessive uterine PG production in nonpregnant bovine endometrium.
Lee
Hwa-Yong
HY
Laboratory of Reproductive Endocrinology, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan.
Acosta
Tomas J
TJ
Skarzynski
Dariusz J
DJ
Okuda
Kiyoshi
K
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D015237:Dinoprost / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D015149:Tocolytic Agents / Q000494:pharmacology
D015149:Tocolytic Agents; D015237:Dinoprost; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D015232:Dinoprostone; D007213:Indomethacin