INVESTIGADORES
DE NICOLA Alejandro Federico
artículos
Título:
Adrenal hypersensitivity precedes chronic hypercoricism in streptozotocin-induced diabetes mice
Autor/es:
REVSIN Y.; VAN WIJK D; SARAVIA F.; OITZL M.; DE NICOLA A.F.; DE KLOET E.R.
Revista:
ENDOCRINOLOGY
Editorial:
Lippincott
Referencias:
Lugar: USA; 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, we tested 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, we used the
streptozotocin (STZ)-induced diabetes mouse model and measured
hypothalamic-pituitary-adrenal 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.