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Journal of Neuroscience, Vol 16, 1866-1876, Copyright © 1996 by Society for Neuroscience
The inhibitory effect of testosterone on hypothalamic-pituitary-adrenal responses to stress is mediated by the medial preoptic area
V Viau and MJ Meaney
Douglas Hospital Research Center, Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
In gonadectomized (GDX) animals replaced with subcutaneous steroid implants
supplying physiological levels of testosterone (T; 1-10 ng/ml), the
magnitude of adrenocorticotropic hormone (ACTH) and corticosterone (B)
responses to restraint was negatively correlated with the level of T
replacement, reflecting the inhibitory influence of T on
hypothalamic-pituitary-adrenal (HPA) responses to stress. Although T had no
effect on resting-state levels of corticotropin-releasing hormone (CRH) in
the median eminence, arginine vasopressin (AVP) levels were significantly
lower in GDX animals replaced with higher T levels, and the magnitude of
the ACTH response to restraint was strongly correlated with median eminence
levels of AVP. High physiological levels of T increased glucocorticoid
receptor binding in the medial preoptic area (MPOA), with no effect on
mineralocorticoid receptor binding or on glucocorticoid receptor binding in
other regions. Crystalline T or B implants in the MPOA significantly
reduced plasma ACTH and B responses to 10 min of restraint stress compared
with cholesterol-implanted controls. Moreover, B or T MPOA implants also
decreased resting-state levels of AVP but not CRH in the median eminence,
and these effects were correlated with ACTH responses to restraint.
Finally, lesioning the MPOA blocked the inhibitory effects of high
peripheral T levels on ACTH and B responses to restraint. Thus, variations
in the magnitude of HPA responses to stress among males are explained in
part by individual differences in circulating T levels, and the MPOA is a
critical site for this effect via the inhibition of hypophysial AVP.
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