DEXAMETHASONE RESISTANCE AMONG NONHUMAN-PRIMATES ASSOCIATED WITH A SELECTIVE DECREASE OF GLUCOCORTICOID RECEPTORS IN THE HIPPOCAMPUS AND A HISTORY OF SOCIAL INSTABILITY

被引:49
作者
BROOKE, SM
DEHAASJOHNSON, AM
KAPLAN, JR
MANUCK, SB
SAPOLSKY, RM
机构
[1] STANFORD UNIV,DEPT BIOL SCI,STANFORD,CA 94305
[2] WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,WINSTON SALEM,NC 27103
[3] UNIV PITTSBURGH,DEPT PSYCHOL,PITTSBURGH,PA 15260
关键词
STRESS; CORTICOSTEROID RECEPTORS; AUTOREGULATION; DEXAMETHASONE RESISTANCE; PRIMATES; SOCIAL INSTABILITY; SOCIAL BEHAVIOR; ADRENAL STEROIDS; ADRENAL STEROID RECEPTORS;
D O I
10.1159/000126743
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We have studied some of the neuroendocrine and social correlates of dexamethasone resistance in a nonhuman primate population. Subjects were 51 male Macaca fascicularis monkeys with known behavioral histories and who had been given dexamethasone (DEX) suppression tests a week prior to killing. We compared the subset of monkeys who were most DEX responsive (post-DEX cortisol values of 3.1 +/- 0.5 mu g/dl) versus a DEX-resistant subset (cortisol values of 9.2 +/- 2.0 mu g/dl); we found two features that distinguished these groups: (a) DEX-resistant monkeys had significantly fewer available glucocorticoid receptor (GR) binding sites in the hippocampus; they did not differ in numbers of mineralocorticoid receptor (MR) sites in the hippocampus, nor in numbers for either receptor in the cortex or hypothalamus as a whole. (b) Animals had resided for a number of years in social groups that were either stable or were repeatedly destabilized by changing of group membership; the latter has been shown to constitute a sustained stressor. DEX-resistant animals were more than twice as likely to have come from an unstable group as were DEX-responsive monkeys. Rodent studies have shown that sustained stress can cause a selective downregulatory decrease in the numbers of hippocampal corticosteroid receptors, and that such a loss is associated with DEX resistance. The present data suggest similar associations in the primate, and may be of relevance to the DEX resistance observed in a subset of human depressives.
引用
收藏
页码:134 / 140
页数:7
相关论文
共 39 条
  • [21] KAPLAN JR, 1983, SCIENCE, V220, P733
  • [22] CORTICOSTEROID INHIBITION OF ACTH-SECRETION
    KELLERWOOD, ME
    DALLMAN, MF
    [J]. ENDOCRINE REVIEWS, 1984, 5 (01) : 1 - 24
  • [23] KEVERNE EB, 1982, ADV VIEWS PRIMATE BI
  • [24] LEVINE S, 1989, PSYCHOENDOCRINOLOGY
  • [25] DEXAMETHASONE BIOAVAILABILITY - IMPLICATIONS FOR DST RESEARCH
    LOWY, MT
    MELTZER, HY
    [J]. BIOLOGICAL PSYCHIATRY, 1987, 22 (03) : 373 - 385
  • [26] PLASMA CORTICOSTEROIDS - CHANGES IN CONCENTRATION AFTER STIMULATION OF HIPPOCAMPUS AND AMYGDALA
    MANDELL, AJ
    RAND, RW
    WALTER, RD
    CHAPMAN, LF
    [J]. SCIENCE, 1963, 139 (356) : 1212 - &
  • [27] MCEWEN B, 1986, PHYSIOL REV, V6, P1121
  • [28] MENDOZA SP, 1979, PSYCHONEUROENDOCRINO, V3, P221
  • [29] NEURO-ENDOCRINE EFFECTS OF INTRAVENOUS OVINE CORTICOTROPIN-RELEASING FACTOR IN AFFECTIVE-DISORDER PATIENTS AND NORMAL CONTROLS
    RISCH, SC
    GOLSHAN, S
    RAPAPORT, MH
    DUPONT, R
    OUTENREATH, R
    GILLIN, JC
    JANOWSKY, DS
    [J]. BIOLOGICAL PSYCHIATRY, 1988, 23 (07) : 755 - 758
  • [30] HEMORRHAGE IN NEWBORN LAMBS - EFFECTS ON ARTERIAL BLOOD-PRESSURE, ACTH, CORTISOL, AND VASOPRESSIN
    ROSE, JC
    MORRIS, M
    MEIS, PJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1981, 240 (06): : E585 - E590