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Adrenal Phenylethanolamine N ‐Methyltransferase Induction in Relation to Glucocorticoid Receptor Dynamics: Evidence that Acute Exposure to High Cortisol Levels Is Sufficient to Induce the Enzyme
Author(s) -
Betito Katia,
Diorio Josie,
Meaney Michael J.,
Boksa Patricia
Publication year - 1992
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1992.tb10062.x
Subject(s) - medicine , endocrinology , phenylethanolamine , glucocorticoid receptor , glucocorticoid , phenylethanolamine n methyltransferase , receptor , chemistry , receptor antagonist , antiglucocorticoid , biology , antagonist , tyrosine hydroxylase , dopamine
Glucocorticoids (GCs) are thought to regulate, in a permissive fashion, the basal activity of adrenal medullary phenylethanolamine N ‐methyltransferase (PNMT). However, it is unclear whether a large short‐term increase in GC release, such as occurs during an acute stress response, may also play a role in PNMT regulation. The present study investigated how the GC influence over PNMT activity varies in relation to dynamic changes in the hormone‐receptor signal. Using [ 3 H]dexamethasone (DEX) and [ 3 H]RU 28362 as radioligands, we have confirmed the presence of GC receptors in bovine adrenal medullary cells. A concentration‐dependent decline in soluble GC receptor sites and an increase in nuclear uptake of [ 3 H]DEX were found in response to GC levels as low as 5 × 10 −8 M . The loss of soluble sites plateaued between 5 × 10 −8 and 10 −6 M cortisol, with further losses occurring at 10 −5 and at 10 −4 M . The functional consequence of GC receptor binding was confirmed by measuring PNMT activity following 3‐day exposure to cortisol. The pattern of PNMT induction was similar to that seen with GC receptor occupancy; at cortisol concentrations between 10 −8 and 10 −5 M , PNMT induction was at a plateau, with a further increase in activity at 10 −4 M . The increase in PNMT activity following 3‐day exposure to low (10 −7 M ) and high (5 × 10 −5 , 10 −5 M ) cortisol was blocked by the GC receptor antagonist RU 38486, suggesting a GC receptor‐mediated event. Finally, a short (2 h) pulse of GC, which mimics the time course of physiological elevation of GC following acute stress, elevated adrenal medullary PNMT activity measured 3 days later. Therefore, our results provide novel evidence that short‐term exposure of adrenal medullary cells to high cortisol levels can elevate PNMT activity.