Mouse Strain Susceptibility to Gonadectomy-Induced Adrenocortical Tumor Formation Correlates with the Expression of GATA-4 and Luteinizing Hormone Receptor

Autor: Nafis A. Rahman, Elena Genova, Louis J. Muglia, David B. Wilson, Susan B. Porter-Tinge, Ilpo Huhtaniemi, Sanne Kiiveri, Malgorzata Bielinska, Helka Parviainen, Markku Heikinheimo
Rok vydání: 2003
Předmět:
Male
medicine.medical_specialty
medicine.drug_class
Ovariectomy
In situ hybridization
Biology
medicine.disease_cause
Mice
03 medical and health sciences
0302 clinical medicine
Endocrinology
Species Specificity
Internal medicine
Biomarkers
Tumor
medicine
Animals
Regeneration
RNA
Messenger
Receptor
030304 developmental biology
0303 health sciences
Adrenal gland
Adrenal cortex
Ovary
luteinizing hormone/choriogonadotropin receptor
Steroid 17-alpha-Hydroxylase
Receptors
LH
Adrenal Cortex Neoplasm
Adrenal Cortex Neoplasms
GATA4 Transcription Factor
DNA-Binding Proteins
Gene Expression Regulation
Neoplastic
Mice
Inbred C57BL
medicine.anatomical_structure
Mice
Inbred DBA
030220 oncology & carcinogenesis
Adrenal Cortex
Female
Disease Susceptibility
Gonadotropin
Carcinogenesis
Orchiectomy
Transcription Factors
Zdroj: Endocrinology. 144:4123-4133
ISSN: 1945-7170
0013-7227
Popis: 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 17α-hydroxylase/C17-C20 lyase, an enzyme essential for the production of sex steroids, and inhibin-α 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 17α-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.
Databáze: OpenAIRE
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