Hypothalamic–pituitary–adrenal axis function in pony foals after neonatal ACTH‐induced glucocorticoid overexposure

Abstract

SummaryReasons for performing the study: The effects of overexposure to glucocorticoids during early life of the foal on the subsequent HPA programming of the hypothalamic-pituitary-adrenal axis are unknown. Objectives: To test the hypotheses that excess glucocorticoid exposure in early life subsequently increases both basal plasma concentrations of cortisol and the adrenocortical responsiveness to exogenous adrenocorticotropic hormone (ACTH). Methods: Foals received either saline (0.9% NaCl, n = 9) or long-acting ACTH (0.125 mg i.m. b.i.d., n = 6) for 5 days from Day 1 to increase endogenous cortisol concentrations. Long-term indwelling catheters were inserted under local anaesthesia into the jugular veins of foals aged 2 and 12 weeks. After recovery, short-acting ACTH1-24 was given as a single i.v. injection (2 mg/kg bwt) and blood samples were taken at 5-30 min intervals before and after ACTH administration to measure plasma cortisol concentrations. Results: Basal plasma cortisol concentrations were higher in ACTH-than in saline-treated foals at age 3 weeks, but not at 13 weeks. There were no significant differences in either the time profile or the area under the cortisol curve in response to ACTH between the 2 groups. Conclusions: These data suggest that ACTH-induced overexposure to glucocorticoids during early post natal life of the foal does not have a programming effect on HPA axis function at 13 weeks. In foals, the effects of ACTH-induced overexposure to glucocorticoids, if any, may not become apparent until much later in life in a long-lived species such as the horse. Potential relevance: These studies suggest that clinical and other stressful conditions that raise plasma cortisol concentrations during early life are unlikely to programme cardiovascular and metabolic function in horses in the short term.

Neonatal glucocorticoid overexposure programs pituitary-adrenal function in ponies

“…Before neonatal treatment began, there were no significant differences in mean body weight (28.2 AE 2.2 kg and 28.5 AE 2.3 kg; P > 0.05) or basal plasma concentration of cortisol (24.5 AE 3.9 ng/mL and 32.4 AE 8.1 ng/mL; P ¼ 0.09) between foals receiving saline (n ¼ 8) or ACTH, respectively (n ¼ 9) [7]. During the 5-d period of neonatal treatment, the mean plasma cortisol concentration was higher in ACTH-treated foals (190.5 AE 15.3 ng/mL, n ¼ 8) than saline-treated foals (20.6 AE 1.2 ng/mL, n ¼ 9, P < 0.001) [7].…”

“…During the 5-d period of neonatal treatment, the mean plasma cortisol concentration was higher in ACTH-treated foals (190.5 AE 15.3 ng/mL, n ¼ 8) than saline-treated foals (20.6 AE 1.2 ng/mL, n ¼ 9, P < 0.001) [7].…”

“…Plasma cortisol concentrations were determined using a commercial assay kit (Coat-A-Count Cortisol; Siemens Medical Solutions Diagnostics, Los Angeles, CA) validated for equine plasma [7]. The sensitivity of this assay was 0.04 ng/mL.…”

“…Seventeen ponies born spontaneously at full term (approximately 325-330 d) were used. After birth (1 d) foals were weighed and received either saline (0.9% NaCl, n ¼ 8, 4 females and 4 males) or long acting ACTH (Depot Synacthen; Alliance Pharmaceuticals Ltd, Wiltshire, UK; 0.125 mg intramuscularly twice daily, n ¼ 9, 5 females and 4 males) for 5 d to maintain an endogenous raise in cortisol concentrations [7]. Plasma cortisol concentrations were determined daily in jugular venous blood samples (4 mL).…”

“…Horses may, therefore, be more susceptible to glucocorticoid programming during the neonatal rather than the fetal period of development. Neonatal cortisol overexposure induced by adrenocorticotropic hormone (ACTH) administration to healthy foals has been shown to alter pancreatic b-cell function up to 13 wk later but had little apparent effect on HPA axis function at 13 wk of age [7,8]. However, its effects on the HPA may not become evident until much later in life in long-lived species [9,10].…”