Abstract |
A somatic cell genetic approach was used to study the role of cyclic nucleotides in adrenal steroidogenesis. 8-Bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated steroidogenesis (K'd=0.1 mM) in cultured mouse adrenocortical tumor cells (Clone Y1). In addition, 8BrcAMP inhibited Y1 cell growth and caused Y1 cell monolayers to assume a rounded morphology. As a consequence, 8BrcAMP (at concentrations greater than or equal to 0.4 mM) reduced the relative plating efficiency of Y1 cells to less than 10(-5). Y1 cells were mutagenized with ethyl methanesulfonate (300 microgram/ml) and grown in the presence of 0.4 mM 8BrcAMP. A surviving colony (8BrcAMPr-1) was shown to be resistant to growth inhibition (relative plating efficiency at 1.0 mM 8BrcAMP=50 percent)) and to morphological changes induced by 8BrcAMP. 8BrcAMPr-1 cells had diminished steroidogenic responses to cyclic nucleotides and to ACTH (less than or equal to 33 percent of maximum). In 8BrcAMP(R)-1 cells, adenylate cyclase activity remained responsive to ACTH, and cyclic AMP phosphodiesterase activity was not increased. These data suggest that 8BrcAMPr-1 cells are defective at a point common to cyclic AMP action on growth, morphology and steroidogenesis. The associated decrease in responsiveness of the steroidogenic pathway to ACTH suggests that ACTH-regulated steroidogenesis is via a cyclic nucleotide-mediated mechanism.
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Authors | B P Schimmer, J Tsao, M Knapp |
Journal | Molecular and cellular endocrinology
(Mol Cell Endocrinol)
Vol. 8
Issue 2
Pg. 135-45
(Aug 1977)
ISSN: 0303-7207 [Print] Ireland |
PMID | 200506
(Publication Type: Journal Article)
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Chemical References |
- DNA, Neoplasm
- Steroids
- Xanthines
- Adrenocorticotropic Hormone
- Cyclic AMP
- 3',5'-Cyclic-AMP Phosphodiesterases
- Adenylyl Cyclases
- Bromine
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Topics |
- 3',5'-Cyclic-AMP Phosphodiesterases
(metabolism)
- Adenylyl Cyclases
(metabolism)
- Adrenal Cortex Neoplasms
(metabolism)
- Adrenal Gland Neoplasms
(metabolism)
- Adrenocorticotropic Hormone
(pharmacology)
- Animals
- Bromine
- Cell Survival
(drug effects)
- Cells, Cultured
- Cyclic AMP
(pharmacology)
- DNA, Neoplasm
(metabolism)
- Drug Resistance
- Mice
- Mutation
- Steroids
(biosynthesis)
- Xanthines
(pharmacology)
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