Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-8-22
pubmed:abstractText
Certain inbred strains of mice, including DBA/2J, develop adrenocortical tumors in response to gonadectomy. Spindle-shaped cells with limited steroidogenic capacity, termed A cells, appear in the subcapsular region of the adrenal gland, followed by sex steroid-producing cells known as B cells. These changes result from unopposed gonadotropin production by the pituitary, but the adrenocortical factors involved in tumorigenesis have not been characterized. GATA-4, a transcription factor normally expressed in fetal, but not adult, adrenocortical cells, was found in neoplastic cells that proliferate in the adrenal cortex of gonadectomized DBA/2J mice. GATA-4 mRNA was detected in the adrenal glands of female mice 0.5 months after ovariectomy and reached a maximum by 4 months. Castrated male mice developed adrenocortical tumors more slowly than gonadectomized females, and the onset of GATA-4 expression in the adrenal was delayed. In situ hybridization and immunohistochemistry revealed GATA-4 mRNA and protein in A and B cells, but not in normal adrenocortical cells. mRNA encoding another factor associated with adrenocortical tumorigenesis, LH receptor (LHR), was detected in A and B cells. In addition, transcripts for P450 17 alpha-hydroxylase/C17-C20 lyase, an enzyme essential for the production of sex steroids, and inhibin-alpha were found in B cells. Unilateral ovarian regeneration, a phenomenon known to occur in gonadectomized mice, was observed in a subset of DBA/2J mice undergoing complete ovariectomy. In these animals, adrenocortical tumor progression was arrested; A cells and GATA-4 expression were evident, but there was no expression of LHR or P450 17 alpha-hydroxylase/C17-C20 lyase. Strain susceptibility to adrenocortical tumorigenesis (DBA/2J >> FVB/N) correlated with the expression of GATA-4 and LHR, implicating these factors in the process of adrenocortical neoplasia in response to continuous gonadotropin stimulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
144
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4123-33
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12933687-Adrenal Cortex, pubmed-meshheading:12933687-Adrenal Cortex Neoplasms, pubmed-meshheading:12933687-Animals, pubmed-meshheading:12933687-DNA-Binding Proteins, pubmed-meshheading:12933687-Disease Susceptibility, pubmed-meshheading:12933687-Female, pubmed-meshheading:12933687-GATA4 Transcription Factor, pubmed-meshheading:12933687-Gene Expression Regulation, Neoplastic, pubmed-meshheading:12933687-Male, pubmed-meshheading:12933687-Mice, pubmed-meshheading:12933687-Mice, Inbred C57BL, pubmed-meshheading:12933687-Mice, Inbred DBA, pubmed-meshheading:12933687-Orchiectomy, pubmed-meshheading:12933687-Ovariectomy, pubmed-meshheading:12933687-Ovary, pubmed-meshheading:12933687-RNA, Messenger, pubmed-meshheading:12933687-Receptors, LH, pubmed-meshheading:12933687-Regeneration, pubmed-meshheading:12933687-Species Specificity, pubmed-meshheading:12933687-Steroid 17-alpha-Hydroxylase, pubmed-meshheading:12933687-Transcription Factors, pubmed-meshheading:12933687-Tumor Markers, Biological
pubmed:year
2003
pubmed:articleTitle
Mouse strain susceptibility to gonadectomy-induced adrenocortical tumor formation correlates with the expression of GATA-4 and luteinizing hormone receptor.
pubmed:affiliation
Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't