Sr. Bornstein et al., Deletion of tyrosine hydroxylase gene reveals functional interdependence of adrenocortical and chromaffin cell system in vivo, P NAS US, 97(26), 2000, pp. 14742-14747
Citations number
57
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Catecholamines are produced in the medulla of the adrenal gland and may par
ticipate in the intraglandular regulation of its cortex We analyzed the adr
enal structure and function of albino tyrosine hydroxylase-null (TH-null) m
ice that are deficient in adrenal catecholamine production. Adrenal catecho
lamines were markedly reduced, and catecholamine histofluorescence was abro
gated in 15-day-old TH-null mice. Chromaffin cell structure was strikingly
altered at the ultrastructural level with a depletion of chromaffin vesicle
s and an increase in rough endoplasmic reticulum compared with wild-type mi
ce. Remaining chromaffin vesicles lined up proximally to the cell membrane
in preparation for exocytosis providing a "string-of-pearls" appearance. Th
ere was a 5-fold increase in the expression of proenkephalin mRNA(502.8 +/-
142% vs. 100 +/- 17.5%, P = 0.016) and a 2-fold increase in the expression
of neuropeptide Y(213.4 +/- 41.2% vs. 100 +/- 59.9%, P = 0.014) in the TH-
null animals as determined by quantitative TaqMan (Perkin-Elmer) PCR. Accor
dingly, immunofluorescence for met-enkephalin and neuropeptide tyrosine in
these animals was strongly enhanced. The expression of phenylethanolamine I
V-methyl transferase and chromogranin B mRNA was similar in TH-null and wil
d-type mice. In TH-null mice, adrenocortical cells were characterized by an
increase in liposomes and by tubular mitochondria with reduced internal me
mbranes, suggesting a hypofunctional state of these steroid-producing cells
. In accordance with these findings, plasma corticosterone levels were decr
eased. plasma ACTH levels were not significantly different in TH-null mice.
In conclusion, both the adrenomedullary and adrenocortical systems demonst
rate structural and functional changes in catecholamine deficient TH-null m
ice, underscoring the great importance of the functional interdependence of
these systems in vivo.