Stressful stimuli evoke complex endocrine, autonomic, and behavioral responses that are extremely variable and specific depending on the type and nature of the stressors. We first provide a short overview of physiology, biochemistry, and molecular genetics of sympatho-adrenomedullary, sympatho-neural, and brain catecholaminergic systems. Important processes of catecholamine biosynthesis, storage, release, secretion, uptake, reuptake, degradation, and transporters in acutely or chronically stressed organisms are described. We emphasize the structural variability of catecholamine systems and the molecular genetics of enzymes involved in biosynthesis and degradation of catecholamines and transporters. Characterization of enzyme gene promoters, transcriptional and posttranscriptional mechanisms, transcription factors, gene expression and protein translation, as well as different phases of stress-activated transcription and quantitative determination of mRNA levels in stressed organisms are discussed. Data from catecholamine enzyme gene knockout mice are shown. Interaction of catecholaminergic systems with other neurotransmitter and hormonal systems are discussed. We describe the effects of homotypic and heterotypic stressors, adaptation and maladaptation of the organism, and the specificity of stressors (physical, emotional, metabolic, etc.) on activation of catecholaminergic systems at all levels from plasma catecholamines to gene expression of catecholamine enzymes. We also discuss cross-adaptation and the effect of novel heterotypic stressors on organisms adapted to long-term monotypic stressors. The extra-adrenal nonneuronal adrenergic system is described. Stress-related central neuronal regulatory circuits and central organization of responses to various stressors are presented with selected examples of regulatory molecular mechanisms. Data summarized here indicate that catecholaminergic systems are activated in different ways following exposure to distinct stressful stimuli.

https://www.physiology.org/doi/pdf/10.1152/physrev.00042.2006

Catecholaminergic Systems in Stress: Structural and Molecular Genetic Approaches

The neural crest gives rise to three major adrenergic cell types: sympathetic principal neurons, adrenal chromaffin cells, and small intensely fluorescent (SIF) cells. All of these derivatives synthesize and store catecholamines, but they differ in numerous other characteristics. SIF cells appear intermediate in phenotype between the other two. We have examined the role of several environmental factors in the differentiation of sympathetic principal neurons and adrenal chromaffin cells. In previous studies of young rat adrenal chromaffin cells in dissociated cell culture, differentiated characteristics such as the presence of the enzyme phenylethanolamine N-methyltransferase (PNMT), epinephrine (E) synthesis, and large catecholamine storage vesicles were not well maintained. Here we describe long-term culture of chromaffin cells which, in the presence of micromolar glucocorticoid, maintained all of these characteristics. In addition, chromaffin cells of a variety of ages were found to be dependent on glucocorticoid for long-term survival in culture. In the absence of glucocorticoid, many adrenal chromaffin cells from neonatal rats could be rescued by nerve growth factor (NGF) administration. They extended neurites, as previously described by Unsicker and colleagues (Unsicker, K., B. Krisch, U. Otten, and H. Thoenen (1978) Proc. Natl. Acad. Sci. U.S.A. 75: 3498–3502). In contrast to previous studies, however, with long-term exposure to NGF these cells became indistinguishable from mature sympathetic neurons, as judged by the following morphological and biochemical criteria: increased cell size and loss of intense CA fluorescence in their cell bodies; acquisition of characteristic neuronal ultrastructure, including morphologically specialized synapses; loss of chromaffin granules, PNMT, and E synthesis; and acquisition of neuron markers, including tetanus toxin labeling and immunoreactivity to neurofilament protein. This conversion to neurons was markedly enhanced by addition of a non-neuronal cell conditioned medium (CM) containing a neurite-promoting factor, which acted by increasing the NGF responsiveness of the chromaffin cells. Even chromaffin cells from adult rats, which are known to grow few processes in response to NGF alone, became neuronal in the presence of this CM plus NGF. While converting to neurons, adrenal chromaffin cells transiently assumed an intermediate phenotype resembling type I SIF cells, which suggests particular developmental relationships between the different cell types of the sympathoadrenal lineage.

https://www.jneurosci.org/content/jneuro/5/8/2119.full.pdf

Environmental influences in the development of neural crest derivatives: glucocorticoids, growth factors, and chromaffin cell plasticity

Regulation of tyrosine hydroxylase mRNA by glucocorticoid and cyclic AMP in a rat pheochromocytoma cell line. Isolation of a cDNA clone for tyrosine hydroxylase mRNA.

The past twelve years have been exciting for those interested in the classical question, “How much do our visual capacities depend on innate developmental factors, how much on the moulding effects of visual experience?” Recent papers1–4 have settled some issues, but may start new waves of controversy, and this is the occasion for writing this review.

Visual experience and cortical development.

Glucocorticoid hormones are important regulators of brain development and ageing. Here we show that dexamethasone, a synthetic glucocorticoid, differentially affects the expression of nerve growth factor (NGF) in cultured neurons and astrocytes. Dexamethasone increased the levels of NGF mRNA in cultured hippocampal neurons in a time- and concentration-dependent manner, whereas it down-regulated the NGF mRNA levels in astrocytes. However, dexamethasone had no effect on the mRNA levels of brain-derived neurotrophic factor in the hippocampal neurons. Aldosterone, a mineralocorticoid, in higher concentrations also up-regulated NGF mRNA levels in the hippocampal neurons. Dexamethasone increased the levels of NGF mRNA in the rat hippocampus in vivo, but not to the same extent as observed with kainic acid, a glutamate receptor agonist. There is no apparent diurnal rhythm in the hippocampal NGF protein levels corresponding to circadian variations in the levels of glucocorticoid hormones in serum. The increase in NGF mRNA in the hippocampus in vivo following dexamethasone treatments may reflect the physiological response of hippocampal neurons to high glucocorticoid levels reached under conditions of stress.

Differential Regulation of Nerve Growth Factor (NGF) Synthesis in Neurons and Astrocytes by Glucocorticoid Hormones.

The trans-synaptic induction of tyrosine hydroxylase [tyrosine 3-monooxygenase; EC 1.14.16.2, L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating)] in adrenal medulla and sympathetic ganglia by short-term (1-2 hr) cold stress (4 degrees) exhibits a circadian rhythm which seems to be causally related to the diurnal changes in adrenal glucocorticoid synthesis. In induction is maximal during the morning hours, when plasma corticoid concentrations (reflecting corticoid synthesis in the adrenal cortex) are minimal. In contrast, initiation of tyrosine hydroxylase induction in sympathetic ganglia is only possible in the afternoon. These observations suggest that tyrosine hydroxylase inducibility in the adrenal medulla is optimal during periods of low corticoid synthesis (the adrenal medulla is exposed to excessively high corticoid concentrations directly originating from the adjacent cortex), whereas in sympathetic ganglia an induction is only possible during the period of high plasma corticoid concentrations. This assumption is supported by the observation that in the first postnatal weeks, when the pituitary--adrenocortical system is not yet operating and plasma corticoid concentrations are low, initiation of tyrosine hydroxylase induction in the adrenal medulla is possible at any time of the day, whereas in sympathetic ganglia it is not possible at all. However, after administration of glycocorticoids initiation of tyrosine hydroxylase induction by short-term cold stress is also possible in newborn animals and in adults during the morning hours. The importance of glucocorticoids as modulators for the initiation of trans-synaptic tyrosine hydroxylase induction can also be deduced from the observation that in sympathetic ganglia kept in organ cultures and induction of the hydroxylase by cholinomimetics is only possible when glycocorticoids are added to the culture medium.

http://www.pnas.org/content/72/4/1415.full.pdf

H Thoenen

Papers

Circadian rhythm of tyrosine hydroxylase induction by short-term cold stress: modulatory action of glucocorticoids in newborn and adult rats.