Post-natal stress-induced endocrine and metabolic alterations in mice at adulthood involve different pro-opiomelanocortin-derived peptides

Autor: Paolo Renzi, Anna Capasso, Giovanni Vanni Frajese, Stefano Vella, Gabriele Campana, Santi Mario Spampinato, Irene Guarino, Alberto Loizzo, Andrea Fortuna, Stefano Loizzo, Gabriella Galietta, Loredana Costa, Flavia Franconi
Přispěvatelé: Loizzo S, Campana G, Vella S, Fortuna A, Galietta G, Guarino I, Costa L, Capasso A, Renzi P, Frajese GV, Franconi F, Loizzo A, Spampinato S.
Rok vydání: 2009
Předmět:
Male
endocrine system
medicine.medical_specialty
Hypothalamo-Hypophyseal System
Pro-Opiomelanocortin
Physiology
Corticotropin-Releasing Hormone
Phosphorothioate Oligonucleotides
Pituitary-Adrenal System
(+)-Naloxone
Adrenocorticotropic hormone
Biochemistry
Diabetes Mellitus
Experimental
Cellular and Molecular Neuroscience
Corticotropin-releasing hormone
chemistry.chemical_compound
Mice
PSYCHOLOGICAL STRESS
Endocrinology
Adrenocorticotropic Hormone
Corticosterone
Internal medicine
medicine
Animals
ANTISENSE OLIGONUCLEOTIDE
Opioid peptide
Naloxone
Maternal Deprivation
HYPOTHALAMUS–PITUITARY–ADRENAL (HPA)
chemistry
Animals
Newborn
Diabetes Mellitus
Type 2
Hypothalamus
Receptors
Opioid
PAIN STRESS
Psychology
hormones
hormone substitutes
and hormone antagonists
Stress
Psychological
Endocrine gland
Hormone
Zdroj: Peptides. 31(11)
ISSN: 1873-5169
Popis: In previous investigations we added a physical stress (mild pain) to the "classical" post-natal psychological stress in male mice, and we found that this combination produced a series of dysmetabolic signs very similar to mild human type-2 diabetes. Here, for the first time we demonstrate that within this diabetes model at least two groups of signs depend on the unbalance of two different endogenous systems. Newborn male mice were daily exposed to stressful procedures for 21 days (brief mother separation plus sham injection). Other groups underwent the same procedure, and also received naloxone (Na) to block μ-δ endogenous receptors, or a phosphorothioate antisense oligonucleotide (AS) directed against pro-opiomelanocortin (POMC)-mRNA [to block adrenocorticotropin (ACTH)- and POMC-derived opioid peptides]. Adult mice which received only post-natal stress increased body weight (+7.5%), abdominal overweight (+74%), fasting glycemia (+43%), plasma corticosterone (+110%), plasma (+169%) and pituitary (+153%) ACTH levels. Conversely, hypothalamic ACTH and corticotropin-releasing hormone (CRH) were reduced (-70% and -75%, respectively). Neonatal AS administration reverted all parameters to control values. Neonatal naloxone had little or no influence on glucose, corticosterone, ACTH, CRH levels, whereas it prevented body overweight and abdominal overweight. We conclude that, within this type-2 diabetes model in male mice at least two endocrino-neurohumoral systems are damaged, one concerning the opioid system, and the other concerning HPA hormones. The use of the two drugs was of primary importance to demonstrate this statement, and to demonstrate that these two groups of signs could be defined as "separate entities" following our complex post-natal stress model.
Databáze: OpenAIRE
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