Hypothalamic-pituitary-adrenal axis function in the Zucker obese rat

Area of Science:

• Neuroendocrinology
• Metabolic Research
• Obesity Pathophysiology

Background:

• Glucocorticoids influence endocrine, metabolic, and behavioral abnormalities in obese Zucker rats.
• Central corticotropin-releasing factor (CRF) tone is implicated in pituitary-adrenal axis and metabolic dysregulation in obesity.

Purpose of the Study:

• To functionally evaluate the hypothalamic CRF system in lean and obese Zucker rat phenotypes.
• To investigate potential alterations in CRF tone and their contribution to obesity-related HPA axis dysregulation.

Main Methods:

• Measured hypothalamic and hypophysial-portal CRF and arginine vasopressin (AVP) levels and mRNA.
• Assessed basal and stimulated CRF release from hypothalamic tissue.
• Evaluated pituitary-adrenal responses to stressors and CRF challenge, and effects of adrenalectomy and corticosterone infusion.

Main Results:

• No differences in hypothalamic CRF/AVP content or mRNA, or basal/stimulated CRF release between phenotypes.
• Obese rats exhibited significantly lower hypophysial-portal CRF and AVP secretion.
• Adrenalectomy increased portal CRF in obese rats; corticosterone more effectively suppressed portal CRF in adrenalectomized obese rats.

Conclusions:

• Obese Zucker rats display reduced hypothalamic CRF tone, indicating HPA axis dysregulation proximal to the hypophysiotropic CRF system.
• Glucocorticoid feedback regulation appears impaired in the obese phenotype.
• Findings suggest a defect in glucocorticoid feedback rather than a primary deficiency in central CRF production.