Linked Life Data

10999829

Source:http://linkedlifedata.com/resource/pubmed/id/10999829

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2000-10-16
pubmed:abstractText
Bone morphogenetic proteins (BMPs), members of the transforming growth factor beta superfamily, were recently shown to be expressed and to regulate steroidogenesis in rat ovarian tissue. The purpose of this study was to investigate the effect of BMP-4 on androgen production in a human ovarian theca-like tumor (HOTT) cell culture model. We have previously demonstrated the usefulness of these cells as a model for human thecal cells. HOTT cells respond to protein kinase A agonists by increased production of androstenedione and with an induction of steroid-metabolizing enzymes. In this investigation, HOTT cells were treated with forskolin or dibutyryl cyclic AMP (dbcAMP) in the presence or absence of various concentrations of BMP-4. The accumulation of androstenedione, progesterone, and 17alpha-hydroxyprogesterone (17OHP) in the incubation medium was measured by RIA. The expression of 17alpha-hydroxylase (CYP17), 3beta-hydroxysteroid dehydrogenase (3betaHSD), cholesterol side-chain cleavage (CYP11A1), and steroidogenic acute regulatory (StAR) protein was determined by protein immunoblotting analysis using specific rabbit polyclonal antibodies. We also examined the expression of BMP receptor subtypes in our HOTT cells using RT-PCR. In cells treated with medium alone, steroid accumulation and steroid enzyme expression was unchanged. In cells treated with BMP alone there was a modest decrease in androstenedione secretion. In the presence of forskolin, HOTT cell production of androstenedione, 17OHP, and progesterone increased by approximately 4.5-, 35-, and 3-fold, respectively. In contrast, BMP-4 decreased forskolin-stimulated HOTT cell secretion of androstenedione and 17OHP by 50% but increased progesterone production 3-fold above forskolin treatment alone. Forskolin treatment led to an increase in CYP17, CYP11A1, 3betaHSD, and StAR protein expression. BMP-4 markedly inhibited forskolin stimulation of CYP17 expression but had little effect on 3betaHSD, CYP11A1, or StAR protein levels. Similar results were observed with the cAMP analog dbcAMP. In addition, BMP-4 inhibited basal and forskolin stimulation of CYP17 messenger RNA expression as determined by RNase protection assay. Other members of the transforming growth factor beta superfamily, including activin and inhibin, had minimal effect on androstenedione production in the absence of forskolin. In the presence of forskolin, activin inhibited androstenedione production by 80%. Activin also inhibited forskolin induction of CYP17 protein expression as determined by Western analysis. We identified the presence of messenger RNA for three BMP receptors (BMP-IA, BMP-IB, and BMP-II) in the HOTT cells model. In conclusion, BMP-4 inhibits HOTT cell expression of CYP17, leading to an alteration of steroidogenic pathway resulting in reduced androstenedione accumulation and increased progesterone production. These effects of BMP-4 seem similar to those caused by activin, another member of the transforming growth factor-beta superfamily of proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3331-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10999829-Androgens, pubmed-meshheading:10999829-Blotting, Western, pubmed-meshheading:10999829-Bone Morphogenetic Protein 4, pubmed-meshheading:10999829-Bone Morphogenetic Proteins, pubmed-meshheading:10999829-Cell Separation, pubmed-meshheading:10999829-Female, pubmed-meshheading:10999829-Humans, pubmed-meshheading:10999829-Inhibins, pubmed-meshheading:10999829-Ovarian Neoplasms, pubmed-meshheading:10999829-Ovary, pubmed-meshheading:10999829-Proteins, pubmed-meshheading:10999829-RNA, pubmed-meshheading:10999829-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10999829-Ribonucleases, pubmed-meshheading:10999829-Steroid 17-alpha-Hydroxylase, pubmed-meshheading:10999829-Steroids, pubmed-meshheading:10999829-Theca Cells, pubmed-meshheading:10999829-Thecoma, pubmed-meshheading:10999829-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Bone morphogenetic protein inhibits ovarian androgen production.
pubmed:affiliation
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, 75235-9032, USA.
pubmed:publicationType
Journal Article, Clinical Trial