Mild chronic post-natal pain induces endocrine and metabolic alterations associated to enlargement in pituitary glands size in adult CD-1 male mice

Background: Human adverse childhood experiences (ACEs) are associated with various types of mental and physical pathological outcomes in adulthood. Among them, they may present the enlargement of the pituitary gland and have been suggested to be a risk factor for the development of Cushing syndrome. Previously, we showed on outbred CD-1 male mice that chronic pain induced during the weaning time by pharmacological experimental design procedures caused endocrine and metabolic alterations in adulthood, suggestive of human mild hypercortisolism. Specifically, we observed an increase in pituitary glands weight and in adrenocorticotropic hormone (ACTH) expression, associated with the lack of the negative feedback mechanisms exerted by corticosterone that controls proopiomelanocortin- derived ACTH secretion. Methods: Here, to better understand the phenotype of mice subjected to early-life pain (ELP), their pituitary glands were examined. Mice tissues and plasma hormones measurements were conducted by ELISA assays. Analysis of brain and pituitary gland was performed using anatomic and diffusion-weighted magnetic resonance imaging. Hematoxylin and eosin-stained sections of pituitary glands were also examined. Results: Mice subjected to ELP showed an increase in total body weight, in pituitary ACTH expression and in plasmatic corticosterone levels. Imaging of the pituitary glands revealed a significant increment of their volume without apparent pathological alterations. Conclusion: The findings of this study may support the role of ELP as a risk factor for ACTH-dependent hypercortisolism in adulthood associated with an enlarged pituitary gland.