Melatonin modulation of the chronic dexamethasone-induced adrenal insufficiency.

IF 3.7 3区 医学 Q2 Medicine Endocrine Pub Date : 2025-01-29 DOI:10.1007/s12020-025-04175-1
Banalata Mohanty, Brijesh Kumar Mishra
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Abstract

Purpose: Chronic exposure to synthetic glucocorticoids/GCs, widely in use to treat many diseases, may compromise the hypothalamic-pituitary-adrenal/HPA axis leading to a condition of adrenal insufficiency/AI. This study demonstrates the efficacy of the melatonin/MEL in amelioration of chronic dexamethasone (DEX)-induced AI.

Methods: Mice (Parkes Strain/Male/8 weeks old/30-33 g) were maintained in four groups (10 mice/group) for 30 days: Group 1/Control received intraperitoneal (i.p) vehicle (alcoholic 0.9% normal saline); Group II/DEX (400 µg/kg BW/day/i.p), Group III/(DEX + MEL 750 µg/kg BW/day/subcutaneous), and Group IV received only MEL. Adrenal, pituitary, and blood samples were collected from six mice/groups. Four mice/groups were subjected to the Lipopolysaccharide (LPS) challenge. Adrenal histology, ACTH immunohistochemistry, and plasma ACTH and corticosterone/CORT levels were measured.

Results: DEX exposure suppressed the pituitary ACTH expression significantly from control as revealed by morphometry and circulating hormones (Density, p < 0.01; size, immunointensity, plasma ACTH, and CORT; p < 0.001). Increased adrenal histopathology indicated probable AI. MEL co-supplementation significantly increased the corticotropes' density (p < 0.05), size (p < 0.001), immunointensity (<0.01), and plasma level of ACTH (p < 0.01) compared to the DEX group. The adreno-cortical width, zona fasciculata cell density and size, and the plasma CORT level (p < 0.001) were also significantly increased. The enhanced CORT response of the HPA axis in the DEX + MEL group compared to the DEX group on the LPS challenge provides support for the MEL restoration of the HPA axis functioning.

Conclusion: Further research on the MEL modulation of the HPA axis may support its role in preventing AI.

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来源期刊
Endocrine
Endocrine 医学-内分泌学与代谢
CiteScore
6.40
自引率
5.40%
发文量
0
期刊介绍: Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
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