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Hypothalamic‐Pituitary‐Adrenal Activation Following Endotoxin Administration in the Developing Rat: A CRH‐Mediated Effect
Author(s) -
Shanks Nola,
Meaney Michael J.
Publication year - 1994
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/j.1365-2826.1994.tb00596.x
Subject(s) - medicine , endocrinology , corticosterone , median eminence , corticotropin releasing hormone , immune system , hormone , chemistry , immunology
The present studies assessed hypothalamic‐pituitary‐adrenal (HPA) responses following immune activation with endotoxin (ip) in three‐day old Long Evans rats. Marked plasma corticosterone (B), adrenocorticotrophic hormone (ACTH) responses and biphasic fluctuations in plasma glucose were maximal at a dose of 0.05 mg/kg. HPA responses peaked between 3–5 h following immune challenge and plasma ACTH and B responses were greater in female than in male rat pups. Plasma levels of corticosterone binding globulin (CBG) were reduced in males and substantially increased in females during the peak HPA response. Changes in plasma glucose were biphasic with slight increases when ACTH and B levels were maximal, but hypoglycemia was evident once plasma B levels returned to resting values. Endotoxin challenge reduced median eminence corticotropin‐releasing hormone (CRH) levels at times corresponding with elevated HPA activity, and prior icv injection of the CRH antagonist, a‐helical CRH, significantly attenuated elevations in plasma ACTH and B. In addition, α‐helical CRH pretreatment completely blocked endotoxin‐induced changes in plasma CBG in both males and females. These findings support the view that endotoxin‐induced HPA activation in the neonate may occur via CRH.