Neonatal glucocorticoid overexposure programs pituitary-adrenal function in ponies.

This research focuses on how overexposure to endogenous glucocorticoids during early life can impact the reactions of the hypothalamic-pituitary-adrenal (HPA) axis in ponies as they age. The findings suggest that neonatal cortisol overexposure, induced by ACTH treatment, changes the functioning of the HPA axis in adult ponies.

Hypothesis and Procedure

• The study was based on the hypothesis that overexposure to endogenous glucocorticoids (which include hormones like cortisol) in neonatal life could potentially alter the reactivity of the HPA axis in ponies when they reach 1 and 2 years of age. The HPA axis is a complex set of interactions between the hypothalamus, the pituitary gland, and the adrenal glands, which are key components of the neuroendocrine system regulating responses to stress among other physiological functions.
• Newborn foals were either treated with a saline solution (serving as the control group) or with a long-acting adrenocorticotropic hormone (ACTH1-24) which was administered intramuscularly twice daily for 5 days following birth. This ACTH treatment aimed to raise cortisol levels 5- to 6-fold, thus simulating the state of cortisol overexposure.

Data Collection and Assessment

• At 1 and 2 years of age, the researchers evaluated the HPA axis function through the administration of short-acting ACTH1-24 and insulin to induce hypoglycemia, which were delivered on separate days. This was done by observing the sample foals’ disparate responses to hormone administration, as it reveals information about their pituitary-adrenal function.
• Blood samples were collected at 5 to 30-minute intervals both prior to and after the drug administration. These samples were used to measure plasma ACTH and cortisol levels, which serve as biomarkers for HPA axis function.
• The measurements indicated no noticeable differences in basal plasma ACTH or cortisol levels, or in the cortisol response to exogenous ACTH1-24 as a result of neonatal treatment or age.

Key Findings

• In their response to hypoglycemia induced by insulin, the increase in plasma ACTH, but not cortisol, was higher in ponies that received ACTH treatment during neonatal stages compared to those treated with saline. This was observed at both 1 and 2 years of age, suggesting that neonatal cortisol overexposure could have long-lasting effects on the HPA axis.
• This study therefore provides evidence that neonatal cortisol overexposure, induced by ACTH treatment, does indeed alter the functioning of the HPA axis in mature ponies.