Linked Life Data

12130558

Source:http://linkedlifedata.com/resource/pubmed/id/12130558

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-7-19
pubmed:abstractText
Hyperandrogenism is known to perturb ovarian physiology resulting in anovulatory conditions. In the ovary, androgens produced by theca-interstitial cells are converted to estrogens in granulosa cells under the influence of FSH and LH. In some of the target organs, including the ovary, androgens are also converted into their 5alpha reduced metabolites. In the present study, we examined the molecular mechanism by which dihydrotestosterone (DHT), a 5alpha reduced metabolite of testosterone, mediates the inhibition of granulosa cell proliferation, using a rat model. Immature female rats were primed with estradiol, followed by DHT administration for 2 d and granulosa cells were cultured in the presence or absence of forskolin. Granulosa cells from the DHT-treated rats showed reduced [(3)H]thymidine incorporation into DNA and reduced cell number in response to forskolin stimulation, compared with control. The decreased responsiveness of DHT-treated granulosa cells to forskolin was not due to increased apoptosis because the expression of cleaved caspase 3 remained the same in both control and DHT-exposed granulosa cells stimulated with forskolin. Forskolin treatment stimulated the expression of cyclin D2 mRNA in control granulosa cells, whereas DHT treatment abolished this response. In vitro DHT treatment of granulosa cells for 48 h resulted in a cell cycle arrest with 70% of cells at G1 phase and 26% at S phase, and control cells exhibited a distribution of 42% and 55% at G1 and S phase, respectively. In conclusion, the present study shows that DHT inhibits the granulosa cell proliferation through a decrease in cyclin D2 mRNA expression, which leads to cell cycle arrest at the G1 phase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
143
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2930-5
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Dihydrotestosterone inhibits granulosa cell proliferation by decreasing the cyclin D2 mRNA expression and cell cycle arrest at G1 phase.
pubmed:affiliation
Department of Obstetrics and Gynecology, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.