title: Contribution of apoptosis to the phenotypic changes of adrenocortical cells in primary culture.
abstract: The aim of this study was to evaluate the occurrence and physiological consequences of apoptosis in primary cultures of bovine adrenocortical cells (of fasciculata-reticularis origin). Under ACTH-free culture conditions, we observed apoptotic cells in the cell layer and the accumulation of apoptotic bodies in the culture medium. These were hardly detectable in ACTH-supplemented cultures. Under ACTH-free conditions, the DNA content of apoptotic bodies collected over 48 h represented up to 10-15% of that of the cell layer at the onset of the culture (as compared to 3% in ACTH-supplemented cultures). Past the fourth day of culture in the absence of ACTh, most cells lacked several markers of their originating fasciculata-reticularis phenotype and progressively evolved to an undifferentiated phenotype. The vast majority of the apoptotic bodies released during the first 4 days of culture were immunoreactive for P450 17 alpha. Inversely, during the same period of time, the proliferating cells (PCNA-positive) did not appear to express P450 17 alpha. Therefore, apoptosis could contribute, together with dedifferentiation, to the phenotype shift observed in ACTH-depleted cultures of adrenal fasciculata-reticularis cells. These observations also characterize this endocrine cell system as an in vitro model for the study of hormone-repressed apoptosis.
authors.affiliation: INSERM Unité 244, CEA, DBMS/BRCE, Centre d'Etudes Nucléaires, Grenoble, France.
authors.forename: A
authors.initials: A
authors.lastname: Negoescu
authors.forename: F
authors.initials: F
authors.lastname: Labat-Moleur
authors.forename: G
authors.initials: G
authors.lastname: Defaye
authors.forename: P
authors.initials: P
authors.lastname: Mezin
authors.forename: C
authors.initials: C
authors.lastname: Drouet
authors.forename: E
authors.initials: E
authors.lastname: Brambilla
authors.forename: E M
authors.initials: EM
authors.lastname: Chambaz
authors.forename: J J
authors.initials: JJ
authors.lastname: Feige
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002417:Cattle; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000648:ultrastructure; D019405:Cytochrome P-450 CYP11B2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D008854:Microscopy, Electron; D010641:Phenotype; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism
chemical_list: D002843:Chromatin; D000324:Adrenocorticotropic Hormone; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase