Disorders of the adrenal cortex

2020 ◽  
pp. 2331-2360
Author(s):  
Mark Sherlock ◽  
Mark Gurnell

Three classes of steroid hormone are produced by the adrenal cortex after uptake of precursor cholesterol from the plasma—mineralocorticoids, glucocorticoids, and sex steroids—with classical endocrine feedback loops controlling their secretion. Glucocorticoids have more diverse and extensive roles than mineralocorticoids, regulating sodium and water homeostasis, glucose and carbohydrate metabolism, inflammation, and stress. These effects are mediated by the interaction of cortisol with ubiquitous glucocorticoid receptors, and the induction or repression of target gene transcription (via glucocorticoid response elements, GREs). Adrenocortical diseases are relatively uncommon, but they have detrimental clinical consequences and can be treated effectively. Hormonal deficiency or excess is usually the result of abnormal secretion.

2005 ◽  
Vol 19 (12) ◽  
pp. 3001-3022 ◽  
Author(s):  
Beth T. Vander Kooi ◽  
Hiroshi Onuma ◽  
James K. Oeser ◽  
Christina A. Svitek ◽  
Shelley R. Allen ◽  
...  

2009 ◽  
Vol 297 (4) ◽  
pp. R1075-R1081 ◽  
Author(s):  
Andrew J. Esbaugh ◽  
Patrick J. Walsh

Unlike most teleosts, gulf toadfish have the capacity to switch from ammoniotely to ureotely as the predominate means of nitrogen excretion during periods of stress. The switch to ureotely is a result of increased glutamine synthetase (GS) mRNA expression/enzyme activity in the liver and muscle, which is initiated by cortisol. Cortisol typically affects gene expression through the action of cortisol-activated transcription factors, such as glucocorticoid receptors, which bind to glucocorticoid response elements (GRE) in the upstream regulatory region of genes. The purpose of the present study was to identify the GRE responsible for increased GS gene expression during crowding/confinement in gulf toadfish using an in vivo luciferase reporter assay. Upstream promoter regions for both the ubiquitous and gill GS isoforms were amplified by PCR. Additionally, an intron was amplified from the ubiquitous GS isoform that suggested the possibility of two discreet transcripts for the mitochondrial and cytoplasmic proteins. When tested via in vivo reporter assays, both the cytoplasmic and mitochondrial ubiquitous GS promoters showed increased luciferase activity during crowding vs. noncrowded controls; the gill GS promoter showed no effects in response to crowding. In silico analysis of the mitochondrial and cytoplasmic ubiquitous GS promoter constructs showed an overlapping section of 565 bp containing two potential GREs. Mutation of either site alone had no effect on luciferase activity vs. wild-type controls. However, when both sites were mutated a significant decrease in luciferase activity was observed. We conclude that two functional GREs combine to confer cortisol-inducible GS expression in the liver of gulf toadfish.


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