Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1994-5-9
pubmed:abstractText
Studies of adrenal steroidogenesis have been facilitated by the availability of immortalized mouse adrenocortical Y-1 cells. We sought to make new, alternative mouse steroidogenic cell lines by genetically targeted tumorigenesis. Transgenic mice were constructed expressing both the SV40 T-antigen and a bacterial neomycin-resistance gene under the control of the promoter for the human P450 cholesterol side-chain cleavage (P450scc) gene, which encodes the first and rate-limiting enzyme in steroidogenesis. Two female transgenic mice expressed T-antigen in various nonsteroidogenic tissues but generated tumors only in the adrenals, suggesting adrenal tumor formation was an early event. Ovarian tissues, which, unlike the adrenal, do not make steroids in fetal or early postnatal life, did not develop tumors. Cell lines derived from the adrenal tumors were resistant to the neomycin analog G418. Clonal sublines are stable, growing easily in monolayers with a doubling time of 24-60 h. The cell lines secrete progesterone and 11-deoxycorticosterone, indicating these cells express the P450scc system, 3 beta-hydroxysteroid dehydrogenase, and 21-hydroxylase activity. However the 21-hydroxylase activity was not mediated by P450c21, as the cells lacked P450c21 mRNA. The cells did not secrete any 11-hydroxylated steroids, although they contained P450c11 beta mRNA. Both the secretion of progesterone and the abundance of P450scc mRNA increase in response to 8-bromo-cAMP, but not to ACTH or angiotensin II. In addition to expression of steroidogenic enzyme mRNAs, one cell line also expresses mouse renin-1 mRNA, making these cells useful for studies of the role of adrenal renin in regulating adrenal steroidogenesis. These findings represent an approach in transgenic mice to develop highly differentiated adrenal cell lines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
97-108
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:8152434-3-Hydroxysteroid Dehydrogenases, pubmed-meshheading:8152434-Adrenal Cortex, pubmed-meshheading:8152434-Adrenal Cortex Hormones, pubmed-meshheading:8152434-Adrenal Gland Neoplasms, pubmed-meshheading:8152434-Animals, pubmed-meshheading:8152434-Antigens, Polyomavirus Transforming, pubmed-meshheading:8152434-Cell Line, pubmed-meshheading:8152434-Cholesterol Side-Chain Cleavage Enzyme, pubmed-meshheading:8152434-Desoxycorticosterone, pubmed-meshheading:8152434-Drug Resistance, pubmed-meshheading:8152434-Female, pubmed-meshheading:8152434-Gene Expression, pubmed-meshheading:8152434-Mice, pubmed-meshheading:8152434-Mice, Transgenic, pubmed-meshheading:8152434-Neomycin, pubmed-meshheading:8152434-Progesterone, pubmed-meshheading:8152434-Promoter Regions, Genetic, pubmed-meshheading:8152434-RNA, Messenger, pubmed-meshheading:8152434-Renin, pubmed-meshheading:8152434-Steroid 21-Hydroxylase
pubmed:year
1994
pubmed:articleTitle
Steroidogenic adrenocortical cell lines produced by genetically targeted tumorigenesis in transgenic mice.
pubmed:affiliation
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143-0556.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't