INVESTIGADORES
SARAVIA Flavia Eugenia
artículos
Título:
Adrenal hypersensitivy precedes hypercorticism in streptozotocin-induced diabetic mice.
Autor/es:
REVSIN Y, VAN WIJK D, SARAVIA F, OITZL M, DE NICOLA AF, DE KLOET ER.
Revista:
ENDOCRINOLOGY
Editorial:
ENDOCRINE SOC
Referencias:
Año: 2008 vol. 149 p. 3531 - 3539
ISSN:
0013-7227
Resumen:
Previous studies have demonstrated that type 1 diabetes is
characterized by hypercorticism and lack of periodicity in
adrenal hormone secretion. In the present study,wetested the
hypothesis that hypercorticism is initiated by an enhanced
release of ACTH leading subsequently to adrenocortical
growth and increased output of adrenocortical hormones. To
test this hypothesis,weused the streptozotocin (STZ)-induced
diabetes mouse model and measured hypothalamic-pituitaryadrenal
axis activity at different time points. The results
showed that the expected rise in blood glucose levels induced
by STZ treatment preceded the surge in corticosterone secretion,
which took place 1 d after diabetes onset. Surprisingly,
circulating ACTH levels were not increased and even below
control levels until 1 d after diabetes onset and remained low
until d 11 during hypercorticism. In response to ACTH (but
not vasopressin), cultures of adrenal gland cells from 11-d
diabetic mice secreted higher amounts of corticosterone than
control cells. Real-time quantitative PCR revealed increased
expression of melanocortin 2 and melanocortin 5 receptors in
the adrenal glands at 2 and 11 d of STZ-induced diabetes. AVP
mRNA expression in the paraventricular nucleus of the hypothalamus
was increased, whereas hippocampal MR mRNA
was decreased in 11-d diabetic animals. GR and CRH mRNAs
remained unchanged in hippocampus and paraventricular
nucleus of diabetic mice at all time points studied. These results
suggest that sensitization of the adrenal glands to ACTH
rather than an increase in circulating ACTH level is the primary
event leading to hypercorticism in the STZ-induced diabetes
mouse model. (Endocrinology 149: 35313539, 2008)Endocrinology 149: 35313539, 2008)