Linked Life Data

18537080

Source:http://linkedlifedata.com/resource/pubmed/id/18537080

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-9-23
pubmed:abstractText
The effect of progestogens on bone is controversial with some studies suggesting an anabolic action while others show no effect. Prereceptor metabolism via localized expression of specific enzymes may have major impact on progesterone action in bone and may explain some of the discrepancies between studies. We therefore investigated the metabolism of progesterone in primary cultures of human osteoblasts and MG-63 osteoblastic cells. Osteoblasts and MG-63 cells were incubated with 4- (14)C-progesterone tracer and 50 nM unlabeled progesterone, and magnitude and pattern of progesterone metabolism were determined by two-dimensional thin-layer chromatography. Conventional and Taqman real-time PCR analysis were used to assess expression of progesterone metabolizing enzymes. In both types of cells the two major metabolic products of progesterone were 20 alpha-dihydroprogesterone and 5 alpha-dihydroprogesterone, but conversion to 3 alpha, 5 alpha- and 3 beta, 5 alpha-tetrahydroprogesterone was also detected. This activity was concomitant with expression of mRNAs for the enzymes AKR1C1, 5 alpha-reductase type 1 and AKR1C2, and 3 beta-HSD type 1 and 3-hydroxysteroid epimerase. In MG-63 cells progesterone metabolism was largely mediated via 5 alpha-reductase. In primary osteoblasts progesterone metabolism was unaffected by treatment with dexamethasone or estradiol, but in MG-63 cells dexamethasone pretreatment increased 5 alpha-reductase activity. Progesterone is subject to extensive intracellular inactivation in human osteoblasts, with potential attenuation of local progesterone receptor responses. Conversely, osteoblasts have the capacity to convert progestogens to metabolites reported to have anabolic actions through the estrogen receptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0018-5043
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
679-84
pubmed:dateRevised
2009-2-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Progesterone is extensively metabolized in osteoblasts: implications for progesterone action on bone.
pubmed:affiliation
Clinical Endocrinology, Internal Medicine, Center for Gastroenterology, Hepatology and Endocrinology, Charité Campus Mitte, Charité University Medicine Berlin, Charitéplatz 1, Berlin, Germany. marcus.quinkler@charite.de
pubmed:publicationType
Journal Article