The influence of corticosteroids on the secretion of corticotrophin and its hypothalamic releasing hormone

Buckingham, Julia C.

doi:10.1113/jphysiol.1979.sp012622

Cited by 58 publications

(42 citation statements)

References 34 publications

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“…Furthermore, the attenuated corticotrophin-releasing activity of hypothalamic extracts from Brattleboro rats is restored by the addition of small (pg) quantities of AVP to the extract (24, 25) whilst systemic administration of desmopressin increases the circulating ACTH concentrations in these rats (26). Our observation that dexamethasone readily abolished the HPA response to stress in both Long Evans and Brattleboro rats is not surprising since, with the treatment regime employed, the steroid would be expected to block the secretion of both AVP and CRF-41 from the parvocellular neurons (14, 27, 28) and to exert effects at the pituitary level (29). The steroid-induced reductions in the basal pituitary-adrenocortical activity described here and elsewhere (30) may be explained similarly.…”

Section: Discussionmentioning

confidence: 99%

A Role for Vasopressin in the Stress‐Induced Inhibition of Gonadotrophin Secretion: Studies in the Brattleboro Rat

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Laycock

Gartside

et al. 1991

J Neuroendocrinology

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The effects of stress on the secretion of adrenocorticotrophin, corticosterone and luteinizing hormone (LH) in rats congenitally lacking hypothalamic vasopressin (Brattleboro rats) and in normal controls of the parent strain (Long Evans) have been compared in an attempt to examine the role of vasopressin in the stress-induced depression of gonadotrophin secretion. In the Long Evans rats, stress (0.6 mg/100 g histamine, ip) initiated, within 5 and 20 min respectively, significant (P< 0.01, Student's t-test) increases in the plasma adrenocorticotrophin and corticosterone concentrations. It also caused a reduction in the serum LH concentration which was maximal a t 5 min. By contrast, in the vasopressin deficient Brattleboro rats, stress had no effect on the serum LH concentration and produced only modest increases in pituitary adrenocortical activity compared with those in Long Evans controls. Pretreatment of both Long Evans and Brattleboro rats with dexamethasone (20 pg1100 g ip, daily for 3 days) effectively abolished the pituitary-adrenal response to stress. The steroid treatment also prevented the stress-induced suppression of LH in the Long Evans rats; indeed, these animals, unlike the vehicle-treated controls, exhibited a rise in serum LH concentration within 5 min of exposure to stress. Stress did not affect the serum LH concentrations in steroid-treated Brattleboro rats. The results confirm previous reports that vasopressin is required for the full expression of the pituitary-adrenocortical response stress. They also provide novel evidence which suggests that vasopressin released in stress contributes to the impairment of gonadotrophin secretion.Stress produces a number of endocrinological changes including activation of the hypothalamo-pituitary-adrenal (HPA) axis and impairment of reproductive function ( I , 2). The stress-induced hypersecretion of adrenocorticotrophin (ACTH) is initiated primarily by two hypothalamic neuropeptides, the 41-amino-acid corticotrophin-releasing factor (CRF-4 1) and arginine vasopressin (AVP). AVP alone is a relatively weak secretagogue (3) but it potentiates markedly the more powerful actions of CRF-41 at the pituitary level (4, 5). The mechanisms responsible for the siress-induced suppression of gonadotrophin release are not clearly understood but data from a number of in vitro and in vivo studies suggest that CRF-41 may be important in this respect. Its site of action appears to be within the hypothalamus (6-10) and may involve an increase in the a-endorphinergic inhibitory tone to the gonadotrophin-releasing hormone (GnRH) neurons (1 1-13). Observations that CRF-41 and AVP are colocalized within the parvocellular neurons of the paraventricular nucleus (14) and that the two neuropeptides are co-secreted in response to certain stressors (15) raise the possibility that AVP may also contribute to the inhibition of luteinizing hormone (LH) release during stress. Accordingly, we have examined the effects of histamine stress on the release of LH and ACTH in rats with he...

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Section: Discussionmentioning

confidence: 99%

A Role for Vasopressin in the Stress‐Induced Inhibition of Gonadotrophin Secretion: Studies in the Brattleboro Rat

Cover

Laycock

Gartside

et al. 1991

J Neuroendocrinology

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“…9 In addition, glucocorticoids produce relatively rapid reduction of corticotropin (adrenocorticotropic hormone, ACTH) release before demonstrable effects of corticotropin biosynthesis, 10,11 as well as rapid inhibition of basal or circadian release of corticotropin-releasing hormone (CRH) from hypothalamus and CRH-stimulated release of corticotropin from the pituitary. 8,12,13 This rapid inhibition is not affected by pretreatment with cycloheximide in a dose that inhibits protein synthesis. 14 This evidence relates well to our demonstrations in human subjects that, after intravenous administration of methylprednisolone, an initial rapid monoexponential decline of cortisol 5 and whole blood histamine occurs.…”

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confidence: 96%

Pharmacokinetics and pharmacodynamic modeling of direct suppression effects of methylprednisolone on serum cortisol and blood histamine in human subjects

Kong

Ludwig

Slaughter

et al. 1989

Clin Pharmacol Ther

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Pharmacodynamic models for "directly suppressive" effects of methylprednisolone are based on the premise that receptor interactions of steroids are followed by immediate suppression of either the circadian secretion of cortisol or the constant rate recirculation of histamine-containing basophils that persists until inhibitory concentrations of methylprednisolone disappear. Methylprednisolone doses of 0, 10, 20, and 40 mg were given as the 21-succinate sodium salt in a balanced crossover study to six normal men. Plasma steroid concentrations and blood histamine were measured simultaneously. Both forms of methylnisolone exhibited linear kinetic parameters. One dynamic model quantitates the baseline circadian pattern and the decline and return of cortisol with similar parameter estimates for all three dose levels. A similar model describes the monoexponential decline and the log-linear return to steady-state baseline of blood histamine. Similar inhibitory concentration values for both effects approximated the equilibrium dissociation constant of in vitro steroid receptor binding. The new models are more physiologically appropriate for these steroid effects than three other models that are commonly employed in pharmacodynamics. Steroid effects generally appear to be receptor mediated with either nongene immediate responses or gene-mediated delayed effects. These models allow quantitation of the rapid effects of steroids with simple equations and common fitted parameters for all steroid dose levels.The diverse immunosuppressive and the antiinflammatory effects of glucocorticoids in human beings complicate the development of realistic and comprehensive kinetic and dynamic models for this class of agents. This is partly because of the complex mode of action of corticosteroids, which involves receptor binding and the formation of second messengers and proteins (which is mediated by deoxyribonucleic acid [DNA]). Such responses are typically characterized by a slow and delayed induction period. This receptorReprint requests: William J. Jusko, PhD, 565 Hochstetter Hall, School of Pharmacy, State University of New York at Buffalo, Buffalo, NY 14260. Presented in part at the Third Annual Meeting of American Association of Pharmaceutical Scientists (AAPS), Orlando, Florida, Oct. 30 to Nov. 3, 1988. NIH Public Access Author ManuscriptClin Pharmacol Ther. Author manuscript; available in PMC 2014 October 23. Published in final edited form as:Clin Pharmacol Ther. 1989 December ; 46(6): 616-628. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript gene mode of action has been successfully modeled for prednisolone effects in rats. 1,2 In human beings, pharmacodynamic modeling of glucocorticoid responses has focused on Sheiner's model 3 of linkage of a hypothetical "effect compartment" to the plasma concentration. This approach has been used to characterize the fall and return of OKT3-and OKT4-positive lymphocytes in peripheral blood after single oral doses of prednisolone. 4 A threshold concentratio...

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“…At this time after adrenalectomy, hypothalamic CRH, and ACTH in pituitary and plasma, are elevated whilst plasma corticosterone is low (Buckingham & Hodges, 1974;Buckingham, 1979) but, in contrast to the decrease in hypothalamic enkephalin content, these changes persist.…”

Section: Discussionmentioning

confidence: 98%

“…It has been shown (Buckingham & Hodges, 1977;Buckingham, 1979) that hypothalamic CRH and pituitary ACTH are reduced by betamethasone but increased by ether stress. However, we found that both minor stress (handling and injection) and dexamethasone treatment increased hypothalamic enkephalin content.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, most criteria of HPA activity measured after shamadrenalectomy indicate changes of shorter duration. For example, plasma corticotrophin (ACTH) and corticosterone concentrations return to normal values 80 min after sham-adrenalectomy whilst plasma corticosterone is significantly depressed 2.5 h after adrenalectomy (Buckingham & Hodges, 1974;Buckingham, 1979). On the other hand, it has been reported (van Dijk, van Wimersma Greidanus, de Kloet & de Wied, 1979) that ACTH levels in hypothalami of rats are decreased 3 days after adrenalectomy or shamadrenalectomy, a time-course similar to that found here for changes in hypothalamic enkephalin.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Adrenalectomy and Hypophysectomy on Enkephalin Content of the Rat Hypothalamus

Gibson

Ginsburg

Hart

et al. 1980

British J Pharmacology

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1Hypothalamic content of enkephalin in rats has been measured by bioassay against methionineenkephalin on field-stimulated mouse vas deferens after acid extraction and purification using Amberlite XAD-2 resin. 2 Surgical stress lowered hypothalamic enkephalin content initially but 6 days after operation the content was higher in sham-operated than in adrenalectomized animals. 3 Corticosteroid replacement therapy showed that hypothalamic enkephalin content was not related directly to circulating corticosteroid levels and that it was increased by the stress of handling and injection.4 Hypothalamic enkephalin content of rats that had undergone hypophysectomy 11 days earlier did not differ from that of intact animals but surgical stress, which lowered content in intact rats and had no effect after adrenalectomy, produced a rise in content in these hypophysectomized animals.5 The ingestion of 0.9% saline, in place of water, by sham-adrenalectomized rats altered the effect of surgical stress on hypothalamic enkephalin content without affecting the resting levels. 6 Of extracts from adrenalectomized rats, 10% contained a substance that behaved atypically on the mouse vas deferens. showing a slower onset and offset of action. The mol. wt. of the substance and sensitivity to naloxone reversal appeared to be similar to enkephalin, but it was resistant to carboxypeptidase-A and protease treatment. 7 It is concluded that the enkephalin content of the hypothalamus is affected by activity in the hypothalamus-pituitary-adrenal system but that it is not related in a simple manner to the levels of corticotrophin releasing hormone, corticotrophin or corticosteroids. IntroductionEnkephalins appear to be neurotransmitters in the brain (Hughes, 1979) and their involvement in the control of the endocrine system is suggested by the ability of morphine to affect anterior pituitary function (George, 1971). There is direct evidence that methionine-enkephalin is capable of increasing plasma concentrations of prolactin (Lien, Fenichel, Garsky, Sarantakis & Grant, 1976) and growth hormone (Dupont, Cusan, Garson, Labrie & Li, 1977) whilst it lowers those of luteinizing hormone and thyrotrophin (Bruni, Van Vugt, Marshall & Meites, 1977). That enkephalins might also be involved in the hypothalamus-pituitary-adrenal (HPA) system is suggested by the enhancement of the corticosterone response to ether stress produced by the intracerebroventricular administration of methionineenkephalin to mice (Gibson, Ginsburg, Hall & Hart, 1979b).Morphine is considered to affect the HPA system by an action in the hypothalamus (George & Way, 1959;Lotti, Kokka & George, 1969). The high content of opioid receptors (Kuhar, Pert & Snyder, 1973) and enkephalin-like immunoreactive material (Elde, Hokfelt, Johanssen & Terenius, 1976) (Table 1). Hypothalami were removed from rats at different times during the day but although the enkephalin content rose between 09 h 30 min and 16 h 00 min the change was not significant. The results in Table I show that there was no...

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The influence of corticosteroids on the secretion of corticotrophin and its hypothalamic releasing hormone

Cited by 58 publications

References 34 publications

A Role for Vasopressin in the Stress‐Induced Inhibition of Gonadotrophin Secretion: Studies in the Brattleboro Rat

A Role for Vasopressin in the Stress‐Induced Inhibition of Gonadotrophin Secretion: Studies in the Brattleboro Rat

Pharmacokinetics and pharmacodynamic modeling of direct suppression effects of methylprednisolone on serum cortisol and blood histamine in human subjects

Effects of Adrenalectomy and Hypophysectomy on Enkephalin Content of the Rat Hypothalamus

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