Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intra- and Intercellular Communication
Adrenal Medullary Hormones
Regulation of Catecholamine Synthesis

Splanchnic nerve stimulation, whose preganglionic fibers innervate The adrenal medulla, triggers the release (via exocytosis) of catecholamines contained in carrier-protein and DBH granules. This stimulation process is controlled by the Hypothalamus and Brainstem; whether it operates via a feedback mechanism remains unproven.

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Fig. 49.3. Metabolic pathways of catecholamines mediated by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). (Reproduced, with permission, from Goldfien A. The adrenal medulla. In: Basic and Clinical Endocrinology. 2nd ed. Greenspan FS, Forsham P. H. [editors]. Appleton and Lange, 1986.)

Nerve stimulation also enhances catecholamine synthesis. Norepinephrine synthesis increases following acute stress; however, The amount of Tyrosine hydroxylase remains unchanged, though its catalytic activity increases. Since tyrosine hydroxylase serves as a substrate for cAMP-dependent protein kinase, this activation is likely attributable to enzyme phosphorylation. Prolonged stress, accompanied by chronically elevated sympathetic nerve activity, leads to the induction (upregulation) of tyrosine hydroxylase. Evidence also points to a similar induction of DBH. The induction of these catecholamine biosynthetic Enzymes acts as an adaptive mechanism to physiological stress and is regulated by neural factors (for tyrosine hydroxylase and DBH induction) and endocrine factors (for PNMT induction).