Effect of Bilateral Adrenalectomy and Corticosteroid Therapy on the Secretion of Corticotrophin-Releasing Factor Activity From the Hypothalamus of the Rat in Vitro

Hillhouse, E. W.; Jones, Melvyn

doi:10.1677/joe.0.0710021

Cited by 39 publications

(15 citation statements)

References 18 publications

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“…Sl-EP has been shown to suppress ACTH and cortisol levels in normal subject (54) and to inhibit both corticotropin-releasing bioactivity (CRB) and iCRH secretion in vitro (55,56 Our results suggesting the presence of a long glucocorticoid-mediated negative feedback loop are consistent with studies conducted with similar or different experimental paradigms. In this regard, it has been shown that CRB content of the hypothalamus and the sensitivity of CRB secretion to various stimuli are increased after adrenalectomy and both effects are reversed by glucocorticoid administration (29,30,33,34). Furthermore, stress-induced and basal CRB content of the hypothalamus and the median eminence are suppressed by glucocorticoid administration (24)(25)(26) or by DEX implants in the median eminence (66).…”

Section: Resultsmentioning

confidence: 99%

Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.

Calogero¹,

Gallucci²,

Gold³

et al. 1988

J. Clin. Invest.

142

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To examine whether the hypothalamic corticotropin-releasing hormone (CRH) neuron is regulated by CRH, by products of the proopiomelanocortin (POMC) gene, and/or by glucocorticoids, we used a rat hypothalamic organ culture system in which rat CRH secretion from single explanted hypothalami was evaluated by an RIA (iCRH) specific for rat CRH. The effects of graded concentrations of ovine CRH (oCRH), adrenocorticotropin hormone (ACTH), 6-endorphin (f-EP), a-melanocyte-stimulating hormone (a-MSH), corticotropin-like intermediate lobe peptide (CLIP), ovine ft-lipotropin (ovine f-LPH), and dexamethasone (DEX) upon unstimulated and serotonin-(5HT), acetylcholine-(ACh), and norepinephrine-(NE) stimulated CRH secretion were determined. oCRH and DEX inhibited unstimulated iCRH secretion with ID50 at the 10-8 M range. ACTH had no detectable suppressive effect at 10-8 M. oCRH, ACTH, and DEX inhibited 5HT-, ACh-, and NE-stimulated iCRH secretion in a dose-dependent fashion.SEEP, a-MSH, and CLIP also inhibited 5HT-induced iCRH secretion. Of the latter peptides, the strongest inhibitor was f-EP and the weakest was CLIP. Ovine fi-LPH had only a weak inhibitory effect on 5HT-induced iCRH secretion. Generally, the concentrations required for 50% suppression of neurotransmitter-stimulated iCRH secretion were significantly lower than those required for a similar suppression of unstimulated iCRH secretion.In conclusion, these data suggest the presence of multiple negative feedback loops involved in the regulation of the hypothalamic CRH neuron: an ultrashort CRH-mediated loop, a short, hypothalamic POMC-derived peptide loop, and a long, glucocorticoid-mediated negative feedback loop. The potency of these negative feedback loops may be determined by the state of activation of the CRH neuron.

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Section: Resultsmentioning

confidence: 99%

Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.

Calogero¹,

Gallucci²,

Gold³

et al. 1988

J. Clin. Invest.

142

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“…The absence of a silent period in our experiments may be because nonstress and stress-induced ACTH secretion are dissociated on the basis of sensitivity to negative corticosteroid feedback effects (10)(11)(12). In more recent experiments, corticosteroid feedback mechanisms were investigated at the hypothalamic level with the technique of the rat hypothalamus in vitro (18,19); both fast and delayed feedback effects on secretion of corticotropin-releasing factor were demonstrated with doses of corticosteroids within, or near, the physiologic range. The results suggested that the fast feedback mechanism acted via the inhibition of release, whereas the delayed feedback mechanism acted via inhibition of both synthesis and release.…”

Section: Resultsmentioning

confidence: 99%

Differential and Integral Corticosteroid Feedback Effects on ACTH Secretion in Hypoadrenocorticism

Fehm¹,

Voigt²,

Kummer³

et al. 1979

J. Clin. Invest.

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A B S T R A C T Recent work suggests the existence of a dual corticosteroid feedback mechanism of stressinduced ACTH secretion in the rat. This possibility led us to study the kinetics of suppression of ACTH levels by corticosteroid administration in patients with nonstress ACTH hypersecretion secondary to hypoadrenocorticism. Cortisol was administered according to different protocols, which were chosen to provide extreme variations of the input signal. By this means, two phases of suppression ofACTH levels could be differentiated. A first decrease occurred without latency whenever, and as long as, plasma cortisol levels were rising. There was a linear regression between the logarithm of the increments in cortisol concentrations and the decrease in ACTH levels per minute (r = 0.951) (differential or rate-sensitive feedback mechanism). Neither the absolute doses of cortisol, nor plasma cortisol concentrations were closely correlated with the degree of suppression of ACTH by this rapid mechanism. A second decrease in ACTH levels began _30 min after corticosteroid administration. In this case there was a significant linear regression between the degree of inhibition of ACTH levels and the cortisol doses (r = 0.997) (integral or dose-sensitive feedback mechanism).The dose-sensitive feedback effects ofdexamethasone were less than might have been predicted from its relative anti-inflammatory potency. No rate-sensitive effects were seen with dexamethasone doses of 1.0 or 1.25 mg.

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“…Glucocorticoid pretreatment inhibited plasma ACTH responses to stress to a significantly greater extent Hillhouse and Jones, 1976;Plotsky and Vale, 1984;Plotsky et al, 1986;Plotsky and Sawchenko, 1987;Sawchenko, 1987a,b;Owens et al, 1990;Imaki et al, 1991). Indeed, this process is considered as a basis for delayed glucocorticoid negative-feedback effects (see Dallman et al, 1992).…”

Section: Discussionmentioning

confidence: 98%

Neonatal endotoxin exposure alters the development of the hypothalamic- pituitary-adrenal axis: early illness and later responsivity to stress

1995

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The long-term consequences of neonatal endotoxin exposure on hypothalamic-pituitary-adrenal axis (HPA) function were assessed in adult female and male Long-Evans rats. At 3 and 5 d of age, pups were administered endotoxin (Salmonella enteritidis, 0.05 mg/kg, i.p.) at a dose that provokes a rapid and sustained physiological response, but with no mortality. As adults, neonatally endotoxin-treated animals exhibited significantly greater adrenocorticotrophic hormone (ACTH) and corticosterone responses to restraint stress than controls. In addition, dexamethasone pretreatment was less effective in suppressing ACTH responses to restraint stress in endotoxin-treated animals than in controls, suggesting decreased negative-feedback sensitivity to glucocorticoids. Neonatal endotoxin treatment elevated resting-state median eminence levels of corticotropin-releasing hormone (CRH) and arginine vasopressin in adult male animals, and arginine vasopressin in both adult males and females. Neonatal exposure to endotoxin also increased CRH mRNA expression in the paraventricular nucleus of the hypothalamus of adult males, with no difference in females. Finally, glucocorticoid receptor density was reduced across a wide range of brain regions in the neonatal endotoxin-treated, adult animals. These data illustrate the interactive nature of immune and endocrine systems during development. It appears that endotoxin exposure during critical stages of development decreases glucocorticoid negative-feedback inhibition of ACTH secretagogue synthesis, thus increasing HPA responsiveness to stress. The implication of these findings is that exposure to gram-negative LPS in early life can alter the development of neural systems which govern endocrine responses to stress and may thereby predispose individuals to stress-related pathology.

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Effect of Bilateral Adrenalectomy and Corticosteroid Therapy on the Secretion of Corticotrophin-Releasing Factor Activity From the Hypothalamus of the Rat in Vitro

Cited by 39 publications

References 18 publications

Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.

Multiple feedback regulatory loops upon rat hypothalamic corticotropin-releasing hormone secretion. Potential clinical implications.

Differential and Integral Corticosteroid Feedback Effects on ACTH Secretion in Hypoadrenocorticism

Neonatal endotoxin exposure alters the development of the hypothalamic- pituitary-adrenal axis: early illness and later responsivity to stress

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