Plasma Corticosteroids: Changes in Concentration after Stimulation of Hippocampus and Amygdala

Mandell, Arnold J.; Chapman, Loring F.; Rand, Robert W.; Walter, Richard D.

doi:10.1126/science.139.3560.1212

Cited by 99 publications

(32 citation statements)

References 2 publications

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“…For example, destruction of the hippocampus or its efferents leads to increases in corticotropin and corticosterone under basal conditions (4-7) and during stress (5,6,8,9). Furthermore, stimulation of most parts of the hippocampus limits the extent of HPA activation to an array of stressors (10)(11)(12)(13). Our (15) and cannot account for the elevated post-stress titers.…”

Section: Resultsmentioning

confidence: 99%

“…Destruction of the hippocampus, for example, leads to hypersecretion of glucocorticoids under basal and stressed conditions (4)(5)(6)(7)(8)(9). Furthermore, stimulation of most parts of the structure inhibits stress-induced HPA activation (10)(11)(12)(13). At least some of this inhibitory influence of the hippocampus represents mediation of feedback inhibition by glucocorticoids.…”

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confidence: 99%

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Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response.

Sapolsky¹,

Krey²,

McEwen³

1984

Proc. Natl. Acad. Sci. U.S.A.

615

333

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The hippocampus is the principal target site in the brain for adrenocortical steroids, as it has the highest concentration of receptor sites for glucocorticoids. The aged rat has a specific deficit in hippocampal glucocorticoid receptors, owing in large part to a loss of corticoid-sensitive neurons. This deficit may be the cause for the failure of aged rats to terminate corticosterone secretion at the end of stress, because extensive lesion and electrical stimulation studies have shown that the hippocampus exerts an inhibitory influence over adrenocortical activity and participates in glucocorticoid feedback. We have studied whether it is the loss of hippocampal neurons or of hippocampal glucocorticoid receptors in the aged rat that contributes most to this syndrome of corticosterone hypersecretion. To do this, we used two model systems for producing reversible glucocorticoid receptor depletion in the hippocampus, and we found that depletion of receptors without inducing cell loss results in corticosterone hypersecretion. Furthermore, correction of the receptor deficit results in normalization of corticosterone secretion. These results focus attention on the hippocampus as an important glucocorticoid sensor in relation to the stress response. They also provide important new physiological correlates for the remarkable plasticity of the hippocampal glucocorticoid receptor system, which is under independent control by corticosterone and by vasopressin.In the mammalian brain, the hippocampus contains the highest concentration of glucocorticoid receptors and retains the highest concentration of [3H]corticosterone after in vivo injection (1). This phenomenon was initially reported in 1968 (2), and considerable speculation still remains regarding the physiological and behavioral significance of the hippocampal uptake system (1, 3). However, the hippocampus has been persistently implicated as an inhibitory influence on the hypothalamic-pituitary-adrenocortical (HPA) axis. Destruction of the hippocampus, for example, leads to hypersecretion of glucocorticoids under basal and stressed conditions (4-9). Furthermore, stimulation of most parts of the structure inhibits stress-induced HPA activation (10-13). At least some of this inhibitory influence of the hippocampus represents mediation of feedback inhibition by glucocorticoids. For example, hippocampectomized subjects are less sensitive to the suppressive effects of exogenous glucocorticoids on HPA secretion (6). Moreover, corticotropin (ACTH) is increased after hippocampectomy and the difference in corticotropin levels between lesioned and sham-lesioned animals is abolished by adrenalectomy, suggesting that the relative increase in corticotropin due to the lesion resulted from lesion-induced disinhibition from corticoid-feedback suppression (5). This evidence that circulating glucocorticoids exert some of their feedback effects via the hippocampus suggests that such actions are mediated by the hippocampal glucocorticoid receptor. Thus, one can postulate that decr...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response.

Sapolsky¹,

Krey²,

McEwen³

1984

Proc. Natl. Acad. Sci. U.S.A.

615

333

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“…Approximately 50% of individuals with Alzheimer's disease (in which there is typically extensive damage to or isolation of the hippocampal formation) hypersecrete GCs (APA Taskforce, 1987), and those with severe damage to the hippocampal formation (as assessed by CT scan) are more hypersecretory than those with less hippocampal damage (De Leon et al, 1988). More direct evidence of the relationship between the human hippocampus and GC hypersecretion comes from an early study, carried out during neurosurgery, which reported that stimulation of the hippocampus inhibited adrenocortical secretion (Mandell et al, 1963). Nevertheless, there has been little sys- , 1989a).…”

Section: Inhibitionmentioning

confidence: 98%

Inhibition of glucocorticoid secretion by the hippocampal formation in the primate

1991

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Inhibition of the adrenocortical axis by glucocorticoids (GCs) occurs at both hypothalamic and suprahypothalamic sites. In the rat, the hippocampus has been shown to be an essential suprahypothalamic site. The present study shows that the hippocampal system serves a similar role in the nonhuman primate. Bilateral lesions that included the hippocampal formation and the parahippocampal cortex; the hippocampal formation, parahippocampal cortex, and the amygdala; or the fornix all produced GC hypersecretion in cynomolgus monkeys. The hypersecretion occurred throughout the day. Moreover, these lesions were also associated with dexamethasone resistance (i.e., GC hypersecretion following administration of the synthetic GC dexamethasone). The hypersecretion could not be attributed to acute surgical trauma, because neither circumscribed lesions of the amygdala nor conjoint lesions of the perirhinal and parahippocampal cortex produced adrenocortical abnormalities. Finally, in agreement with data derived from the rat, the GC hypersecretion following hippocampal lesions was transient. Secretory activity returned to normal levels by 6-15 months in all operated groups. Thus, the primate hippocampal system appears to share some neuroendocrine functions with the rodent.

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“…28 Hippocampal activity normally inhibits the cortisol axis, as demonstrated by electrical stimulation in humans. 29 Damage to hippocampal neurons can therefore be followed by hypercortisolism. This may be due to either a lesioninduced loss of a feedback site in the hippocampal system or an enhanced stimulation causing basal hypersecretion.…”

Section: Discussionmentioning

confidence: 99%

Abnormalities at different levels of the hypothalamic-pituitary-adrenocortical axis early after stroke.

Olsson

Marklund

Gustafson

et al. 1992

Stroke

141

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Background and Purpose: Hypercortisolism is common in stroke patients. The aim of this study was to investigate possible disturbances at different sites within the hypothalamic-pituitary-adrenal axis. We also studied possible associations between hypercortisolism and clinical manifestations of brain dysfunction.Methods: Patients with an acute ischemic stroke (n=16; mean±SD age, 71±11 years) were compared with healthy elderly subjects (n=9). We performed a short adrenocorticotropic hormone (ACTH) test with 0.25 mg 1-24 ACTH injected intravenously and an overnight dexamethasone suppression test with 1 mg dexamethasone given orally at 11 PM.Results: Serum cortisol levels after dexamethasone at 8 AM were significantly higher in stroke patients (p=0.003). The area under the curve for the cortisol response to ACTH was elevated in seven (47%) of stroke patients, and the centered cumulative cortisol response was elevated in three (20%) patients. The area under the curve response correlated significantly to the presence of an acute confusional state and male sex in stroke patients (r s =0.63 and r s =0.62, respectively; p< 0.05), whereas the centered cumulative cortisol response diminished with increasing age (r s =-0.62;p<0.05). Postdexamethasone cortisol levels were significantly correlated to the presence of an acute confusional state and to extensive limb paresis (r s =0.66 and r s =0.62, respectively;p<0.05).Conclusions: There are abnormalities in the cortisol axis both at the central level and at the adrenal level early after stroke. Hypercortisolism is closely associated with cognitive disturbances and extensive motor impairment. (Stroke 1992;23:1573-1576 KEY WORDS • cerebral ischemia • cerebrovascular disorders • cortisol

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Plasma Corticosteroids: Changes in Concentration after Stimulation of Hippocampus and Amygdala

Cited by 99 publications

References 2 publications

Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response.

Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response.

Inhibition of glucocorticoid secretion by the hippocampal formation in the primate

Abnormalities at different levels of the hypothalamic-pituitary-adrenocortical axis early after stroke.

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