title: Hypercortisolism among socially subordinate wild baboons originates at the CNS level.
abstract: Recent studies suggest that the hypercortisolism and dexamathasone resistance of depression arise, at least in part, at the level of the brain, ie, cortisol-releasing factor (CRF) and/or other corticotropin-secretagogues are hypersecreted. This article suggests a similar cause of the hypercortisolism of social subordinance. Two troops of wild olive baboons, living freely in the Serengeti Ecosystem of East Africa, have been under long-term study. Consistently, in stable dominance hierachies, subordinate males are hypercortisolemic relative to dominant animals. Furthermore, hypercortisolemic males are dexamethasone resistant. There are no rank-related difference in cortisol clearance or adrenal sensitivity to corticotropin, suggesting a pituitary and/or neural locus of the hypercortisolism. Subordinate males were shown to secrete less corticotropin in response to a CRF-challenge than did dominant males. Following the logic used in similar studies with depressives, if subordinate males were hypercortisolemic despite decreased pituitary sensitivity to CRF, then this implies that the hyperactivity of the adrenocortical axis is driven at the level of the brain. Furthermore, subordinate males were hyporesponsive to CRF after administration of metyrapone, which blocks cortisol secretion and disinhibits the pituitary from feedback inhibition. Thus, the pituitary appears to have lost sensitivity to CRF itself in these low-ranking males. These observations are interpreted in light of behavioral data suggesting that these subordinate males are under sustained social stress.
authors.affiliation: Department of Biological Sciences, Stanford University, CA 94305.
authors.forename: R M
authors.initials: RM
authors.lastname: Sapolsky
mesh_terms: D000308:Adrenocortical Hyperfunction / Q000097:blood* / Q000503:physiopathology; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D010215:Papio / Q000502:physiology*; D012930:Social Dominance
chemical_list: D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone