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Scanning electron microscopy of induced cell rounding of mouse adrenal cortex tumor cells in culture.

The surface topologies of mouse adrenal cortex tumor cells of primary or clonal origin grown as monolayer cell cultures were observed by scanning electron microscopy following their exposure to substances that effect steroid release and/or cell rounding. ACTH induced cell rounding with a concomitant profuse development of fine microvilli in a non-synchronously dividing cell population. This was less pronounced with other steroidogenic substances and absent in EGTA or trypsin-treated cells. Morphological alterations occurred most rapidly with cAMP and least rapidly with dbcAMP. The rapid development of fine microvilli with ACTH is proposed to be a specific hormone mediated response.

Adrenocorticotropic Hormone↗

The 1994 Upjohn Award Lecture. Molecular and genetic approaches to the study of signal transduction in the adrenal cortex.

This review highlights contributions from my laboratory in which the sites and mechanisms of action of the adrenocorticotropic hormone (ACTH) in the adrenal cortex have been explored. Early studies showing that ACTH stimulates adrenal steroidogenesis by interacting with specific receptors at the cell surface are summarized. Next, the development of a strategy of genetic analysis to define the signalling events that follow ACTH interaction with its receptor is described. This strategy involved the isolation and characterization of mutant adrenal cell lines harboring specific defects in the ACTH-responsive steroidogenic pathway. I describe the isolation and characterization of several of these mutants and demonstrate how these mutants have helped to establish obligatory roles for adenylyl cyclase, cyclic AMP (cAMP), and cAMP-dependent protein kinase in the steroidogenic actions of ACTH. Finally, some of our studies on the regulated expression of the steroidogenic cytochrome P450 enzymes in Y1 adrenal cells are reviewed. These latter studies have led to the discovery of a novel promoter element and transcription factor (designated steroidogenic factor 1) that participates in the coordinate expression of these cytochrome P450 enzymes and that is required for their regulated expression by ACTH and cAMP.

Adrenal Cortex↗

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