PurposeIt has been hypothesized that specific early-life stress (ES) procedures on CD-1 male mice produce diabetes-likealterations due to the failure of negative feedback of glucocorticoid hormone in the pituitary. The aim of this study is toinvestigate the possible mechanism that leads to this pathological model, framing it in a more specific clinical condition.MethodsMetabolic and hypothalamic–pituitary–adrenal-related hormones of stressed mice (SM) have been analyzedimmediately after stress procedures (21 postnatal days, PND) and after 70 days of a peaceful (unstressed) period (90 PND).These data have been compared to parameters from age-matched controls (CTR), and mice treated during ES procedureswith oligonucleotide antisense for pro-opiomelanocortin (AS-POMC).ResultsAt 21 PND, SM presented an increased secretion of hypothalamicCRHand pituitaryPOMC-derivedpeptides, aswell as higher plasmatic levels ofACTHandcorticosteronevs. CTR. At 90 PND, SM showed hyperglycemia, withsuppression of hypothalamicCRH, while pituitary and plasmaticACTHlevels, as well as plasma corticosterone, wereconstantly higher than in CTR. These values are accompanied by a progressive acceleration in gaining total body weight,which became significant vs. CTR at 90 PND together with a higher pituitary weight. Treatment with AS-POMC preventedall hormonal and metabolic alterations observed in SM, both at 21 and 90 PND.ConclusionsThesefindings show that these specific ES procedures affect the negative glucocorticoid feedback in thepituitary, but not in the hypothalamus, suggesting a novel model of ACTH-dependent hypercortisolism that can be preventedby silencing thePOMCgene.

Early post-natal life stress induces permanent adrenocorticotropin-dependent hypercortisolism in male mice / G. Campana, S. Loizzo, A. Fortuna, R. Rimondini, Z. Maroccia, A. Scillitani, A. Falchetti, S.M. Spampinato, L. Persani, I. Chiodini. - In: ENDOCRINE. - ISSN 1355-008X. - (2021). [Epub ahead of print] [10.1007/s12020-021-02659-4]

Early post-natal life stress induces permanent adrenocorticotropin-dependent hypercortisolism in male mice

L. Persani
Penultimo
;
I. Chiodini
Ultimo
2021

Abstract

PurposeIt has been hypothesized that specific early-life stress (ES) procedures on CD-1 male mice produce diabetes-likealterations due to the failure of negative feedback of glucocorticoid hormone in the pituitary. The aim of this study is toinvestigate the possible mechanism that leads to this pathological model, framing it in a more specific clinical condition.MethodsMetabolic and hypothalamic–pituitary–adrenal-related hormones of stressed mice (SM) have been analyzedimmediately after stress procedures (21 postnatal days, PND) and after 70 days of a peaceful (unstressed) period (90 PND).These data have been compared to parameters from age-matched controls (CTR), and mice treated during ES procedureswith oligonucleotide antisense for pro-opiomelanocortin (AS-POMC).ResultsAt 21 PND, SM presented an increased secretion of hypothalamicCRHand pituitaryPOMC-derivedpeptides, aswell as higher plasmatic levels ofACTHandcorticosteronevs. CTR. At 90 PND, SM showed hyperglycemia, withsuppression of hypothalamicCRH, while pituitary and plasmaticACTHlevels, as well as plasma corticosterone, wereconstantly higher than in CTR. These values are accompanied by a progressive acceleration in gaining total body weight,which became significant vs. CTR at 90 PND together with a higher pituitary weight. Treatment with AS-POMC preventedall hormonal and metabolic alterations observed in SM, both at 21 and 90 PND.ConclusionsThesefindings show that these specific ES procedures affect the negative glucocorticoid feedback in thepituitary, but not in the hypothalamus, suggesting a novel model of ACTH-dependent hypercortisolism that can be preventedby silencing thePOMCgene.
Cushing’s syndrome; Early-life stress; Metabolic syndrome; Mouse; Pituitary ACTH hypersecretion;
Settore MED/13 - Endocrinologia
25-feb-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/818410
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