Glucocorticoids, chronic stress, and obesity.
Glucocorticoids either inhibit or sensitize stress-induced activity in the hypothalamo-pituitary-adrenal (HPA) axis, depending on time after their administration, the concentration of the steroids, and whether there is a concurrent stressor input. When there are high glucocorticoids together with a chronic stressor, the steroids act in brain in a feed-forward fashion to recruit a stress-response network that biases ongoing autonomic, neuroendocrine, and behavioral outflow as well as responses to novel stressors. We review evidence for the role of glucocorticoids in activating the central stress-response network, and for mediation of this network by corticotropin-releasing factor (CRF). We briefly review the effects of CRF and its receptor antagonists on motor outflows in rodents, and examine the effects of glucocorticoids and CRF on monoaminergic neurons in brain. Corticosteroids stimulate behaviors that are mediated by dopaminergic mesolimbic "reward" pathways, and increase palatable feeding in rats. Moreover, in the absence of corticosteroids, the typical deficits in adrenalectomized rats are normalized by providing sucrose solutions to drink, suggesting that there is, in addition to the feed-forward action of glucocorticoids on brain, also a feedback action that is based on metabolic well being. Finally, we briefly discuss the problems with this network that normally serves to aid in responses to chronic stress, in our current overindulged, and underexercised society.
Dallman
Mary F
MF
University of California at San Francisco, San Francisco, CA 94143-0444, USA. mary.dallman@ucsf.edu
Pecoraro
Norman C
NC
La Fleur
Susanne E
SE
Warne
James P
JP
Ginsberg
Abigail B
AB
Akana
Susan F
SF
Laugero
Kevin C
KC
Houshyar
Hani
H
Strack
Alison M
AM
Bhatnagar
Seema
S
Bell
Mary E
ME
D000818:Animals; D002908:Chronic Disease; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism*
D005938:Glucocorticoids