Impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter (SVCT2).
Ascorbic acid (vitamin C) is a cofactor required in catecholamine synthesis for conversion of dopamine to norepinephrine by dopamine beta-hydroxylase. Mutant mice lacking the plasma membrane ascorbic acid transporter (SVCT2) have severely reduced tissue levels of ascorbic acid and die after birth. We therefore investigated whether these mice might have impaired synthesis of catecholamines. Levels of catecholamines in brain were unaffected by SVCT2 deficiency. In heart, the only evidence for impaired dopamine beta-hydroxylase activity was a twofold increase in tissue dopamine. An influence of the deficiency on tissue catecholamines was most prominent in the adrenals where norepinephrine was decreased by 50% and epinephrine, by 81%. On the ultrastructural level, adrenal chromaffin cells in SVCT2 null mice showed depletion of catecholamine storage vesicles, increased amounts of rough endoplasmic reticulum, signs of apoptosis, and increased glycogen storage. Decreased plasma levels of corticosterone indicated additional effects of the deficiency on adrenal cortical function. These data show that deranged catecholamine system function in SVCT2 null mice is largely restricted to the adrenal medulla and cannot account for the lethality in these animals. The data, however, establish a crucial role for ascorbic acid in adrenal chromaffin cell function.
Bornstein
Stefan R
SR
Endocrinology, Heinrich-Heine-University, Düsseldorf, Germany. stefan.bornstein@uni-duesseldorf.de
Yoshida-Hiroi
Mayumi
M
Sotiriou
Sotiria
S
Levine
Mark
M
Hartwig
Hans-Georg
HG
Nussbaum
Robert L
RL
Eisenhofer
Graeme
G
D000311:Adrenal Glands / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001921:Brain / Q000378:metabolism; D002395:Catecholamines / Q000096:biosynthesis*; D019439:Chromaffin Cells / Q000502:physiology / Q000648:ultrastructure; D003345:Corticosterone / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics*; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000235:genetics*
D002395:Catecholamines; D029363:Organic Anion Transporters, Sodium-Dependent; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D000324:Adrenocorticotropic Hormone; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine