Studies of the secretion of corticotropin-releasing factor and arginine vasopressin into the hypophysial-portal circulation of the conscious sheep. II. The central noradrenergic and neuropeptide Y pathways cause immediate and prolonged hypothalamic-pituitary-adrenal activation. Potential involvement in the pseudo-Cushing's syndrome of endogenous depression and anorexia nervosa.
Studies were performed to determine the effects of intracerebroventricular norepinephrine (NE) or neuropeptide Y (NPY) on the ovine hypothalamic-pituitary-adrenal (HPA) axis. NE (50 micrograms) increased mean hypophysial-portal corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) levels (1 h, 1.3- and 2.9-fold; 4 h, 2.2- and 5.7-fold) and caused acute and sustained increases in mean plasma ACTH and cortisol. NPY (50 microgram) also increased mean CRF and AVP levels (1 h, 1.4- and 4.2-fold; 4 h, 1.1- and 1.9-fold), increased pituitary-adrenal activity at 1 h, and caused ACTH hypersecretion at 4 h. When added to cultured ovine anterior pituitary cells, NPY neither increased basal ACTH release nor augmented CRF- or AVP-induced ACTH release. We conclude that: (a) activation of either the central noradrenergic or NPY pathways causes an acute and sustained stimulation of the ovine HPA axis; (b) such activation increases the AVP/CRF ratio, suggesting a dominant role for AVP in the ovine stress response; and (c) the central noradrenergic or NPY systems may cause sustained HPA activation by attenuating or disrupting the glucocorticoid negative feedback on those brain areas concerned with regulation of the HPA axis. The possible roles of the central noradrenergic and NPY systems in the etiology of the hypercortisolemia of endogenous depression and anorexia nervosa are discussed.
Liu
J P
JP
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Clarke
I J
IJ
Funder
J W
JW
Engler
D
D
D000818:Animals; D000856:Anorexia Nervosa / Q000209:etiology; D001127:Arginine Vasopressin / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D003480:Cushing Syndrome / Q000209:etiology; D003863:Depression / Q000209:etiology; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012756:Sheep; D012965:Sodium Chloride / Q000494:pharmacology
D009478:Neuropeptide Y; D001127:Arginine Vasopressin; D012965:Sodium Chloride; D003346:Corticotropin-Releasing Hormone; D009638:Norepinephrine