Glucocorticoid-Phenylethanolamine-N-methyltransferase Interactions in Humans

Abstract

Publisher Summary Phenylethanolamine-N-methyltransferase (PNMT) is highly concentrated in the adrenal medulla but has also been demonstrated, although to a much limited extent, in other human tissues, such as lung, heart, kidney, liver, spleen, and pancreas. From in vitro and in vivo studies performed in several animal species, it is well known that in adrenal medulla PNMT activity is dependent on the high levels of glucocorticoids received from the cortex. In vivo data from studies performed in humans are scanty. In children with hypocortisolism because of adrenocotricotropic hormone (ACTH) deficiency, plasma Epi levels are lower. Stimulation of Epi secretion was achieved by intravenous glucagon. Patients with HP were studied while receiving thyroid, glucocorticoid, and sexual steroid replacement therapy. Obtained data confirm that in humans, adrenal PNMT activity seems to depend on the normal cortisol supply to the medulla from the cortex. In fact, in adults affected by HP because of ACTH deficiency, the adrenal medulla secretion is impaired in basal as well as in stimulated conditions. The deficiency of Epi secretion is very probably one of the most important factors causing an impaired response to hypoglycemia in these patients. In fact, the similar Epi/NE ratio found in the adrenal vein of patients with and without chronic hypercortisolism suggests that in humans, a normal cortisol secretion is sufficient to activate PNMT maximally. These results confirm the finding that in the adrenal medullas obtained at surgery from patients with cushing's syndrome (CS), the PNMT activity resulted similar to that found in control human adrenal glands obtained at autopsy.