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Related Experiment Videos

Adrenocortical steroids and the brain.

J W Funder, K Sheppard

    Annual Review of Physiology
    |January 1, 1987
    PubMed
    Summary
    This summary is machine-generated.

    Adrenal steroids like aldosterone and corticosterone have different signal levels, requiring specific mechanisms for aldosterone to be recognized by the mineralocorticoid receptor. In vivo studies reveal tissue-specific aldosterone selectivity, unlike in vitro findings.

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    Area of Science:

    • Endocrinology and Neuroendocrinology
    • Steroid Hormone Action
    • Physiology

    Background:

    • Adrenal steroids, specifically mineralocorticoids and glucocorticoids, exert diverse effects on the brain.
    • A significant disparity exists in circulating levels between aldosterone and glucocorticoids (cortisol/corticosterone).
    • Glucocorticoid levels are 2-3 orders of magnitude higher, partially offset by greater plasma protein binding.

    Purpose of the Study:

    • To investigate the mechanisms underlying aldosterone selectivity in target tissues, particularly the brain.
    • To reconcile in vitro findings of non-selectivity with in vivo observations of aldosterone specificity.
    • To propose models explaining how the mineralocorticoid receptor distinguishes aldosterone from corticosterone.

    Main Methods:

    Related Experiment Videos

  • Comparison of in vitro receptor binding assays with in vivo tissue uptake and retention studies in rats.
  • Analysis of mineralocorticoid receptor (Type I) behavior in both classic target and non-target tissues.
  • Development and evaluation of theoretical models (prebinding and postbinding) for aldosterone selectivity.

    • Main Results:

    • In vitro studies showed Type I receptors in kidney, pituitary, and hippocampus could not differentiate between aldosterone and corticosterone.
    • In vivo studies demonstrated tissue-specific uptake and retention: corticosterone was poorly retained in kidney and pituitary, while aldosterone was well retained across tissues.
    • These in vivo findings provide evidence for aldosterone selectivity in tissues like the kidney and brain.

    Conclusions:

    • Tissue-specific mechanisms are crucial for achieving aldosterone selectivity in vivo, despite in vitro receptor non-selectivity.
    • Proposed 'prebinding' and 'postbinding' models can explain the discrepancy between in vitro and in vivo observations.
    • Understanding adrenal steroid action on the brain requires further hypothesis-driven research to establish coherent physiological principles.