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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-2-14
pubmed:abstractText
Granulosa cells from preovulatory follicles show increased expression of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) at the time of ovulation. As ovulation may be an inflammatory process, this may be a mechanism of local enhancement of the activity of anti-inflammatory glucocorticoids. In this study, we examined direct effects of LH, the proinflammatory cytokine, interleukin-1beta (IL-1beta), and pharmacological activators of protein kinase A (PKA) (forskolin and dibutyryl (db) cAMP) and PKC (LH-releasing hormone and phorbol 12-myristate 13-acetate (PMA)) signalling on the expression of 11betaHSD1 mRNA in vitro. Granulosa cells from immature female rat ovaries were cultured (pretreatment) in serum-free medium 199 containing recombinant human (rh) FSH (1 ng/ml) for 48 h to induce responsiveness to LH. Cell monolayers were then washed and cultured (test treatment) for a further 12 h in the presence of rhLH (0-100 ng/ml), IL-1beta (0-50 ng/ml), or both. Total RNA was extracted from granulosa cell monolayers and taken for quantitative ribonuclease protection analysis of 11betaHSD1 mRNA. The low level of 11betaHSD1 mRNA detectable in unstimulated (control) cultures was increased approximately twofold by the 48-h pretreatment with rhFSH. Subsequent exposure to rhLH (1-100 ng/ml) for a further 12 h dose-dependently increased 11betaHSD1 mRNA expression by an additional two- to threefold. Forskolin (10 microM), db-cAMP (2 mM), LH-releasing hormone (LHRH; 1 microM) and PMA (200 nM) were also stimulatory. IL-1beta (0.05-50 ng/ml) stimulated 11betaHSD1 mRNA expression in a dose-related manner, both in the absence and in the presence of rhLH (3 ng/ml). The interaction between IL-1beta (5 ng/ml) and rhLH (3 ng/ml) was additive. Co-treatment with a 50-fold excess of IL-1 receptor antagonist fully reversed the action of IL-1beta. We conclude that 11betaHSD1 mRNA expression in functionally mature granulosa cells is directly stimulated by gonadotrophins and IL-1beta in vitro, potentially involving post-receptor signalling via PKA- and PKC-mediated pathways. Thus both LH and IL-1beta may serve physiological roles in the upregulation of 11betaHSD1 gene expression by granulosa cells in ovulatory follicles.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/11-beta-Hydroxysteroid..., http://linkedlifedata.com/resource/pubmed/chemical/Bucladesine, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Activators, http://linkedlifedata.com/resource/pubmed/chemical/Follicle Stimulating Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Forskolin, http://linkedlifedata.com/resource/pubmed/chemical/Gonadotropin-Releasing Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxysteroid Dehydrogenases, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1, http://linkedlifedata.com/resource/pubmed/chemical/Luteinizing Hormone, http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Testosterone, http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-0795
pubmed:author
pubmed:issnType
Print
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
417-23
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10588815-11-beta-Hydroxysteroid Dehydrogenases, pubmed-meshheading:10588815-Animals, pubmed-meshheading:10588815-Bucladesine, pubmed-meshheading:10588815-Cells, Cultured, pubmed-meshheading:10588815-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:10588815-Dose-Response Relationship, Drug, pubmed-meshheading:10588815-Enzyme Activators, pubmed-meshheading:10588815-Female, pubmed-meshheading:10588815-Follicle Stimulating Hormone, pubmed-meshheading:10588815-Forskolin, pubmed-meshheading:10588815-Gene Expression Regulation, Enzymologic, pubmed-meshheading:10588815-Gonadotropin-Releasing Hormone, pubmed-meshheading:10588815-Granulosa Cells, pubmed-meshheading:10588815-Hydroxysteroid Dehydrogenases, pubmed-meshheading:10588815-Interleukin-1, pubmed-meshheading:10588815-Luteinizing Hormone, pubmed-meshheading:10588815-Protein Kinase C, pubmed-meshheading:10588815-RNA, Messenger, pubmed-meshheading:10588815-Rats, pubmed-meshheading:10588815-Rats, Wistar, pubmed-meshheading:10588815-Recombinant Proteins, pubmed-meshheading:10588815-Stimulation, Chemical, pubmed-meshheading:10588815-Testosterone, pubmed-meshheading:10588815-Tetradecanoylphorbol Acetate
pubmed:year
1999
pubmed:articleTitle
Regulation of 11beta-hydroxysteroid dehydrogenase type 1 gene expression by LH and interleukin-1beta in cultured rat granulosa cells.
pubmed:affiliation
Reproductive Medicine Laboratory, Department of Reproductive and Developmental Sciences, University of Edinburgh Centre for Reproductive Biology, 37 Chalmers Street, Edinburgh EH3 9EW, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't