Regulation Of ACTH Secretion Research Articles

Effect of central naloxone on hormone and blood pressure responses to hemorrhage in conscious sheep

The role of the brain opioid system in the control of hypothalamic-pituitary-adrenal activity was studied in 10 conscious sheep with an indwelling cannula in a cerebral lateral ventricle. On separate days, sheep received infusions of artificial CSF (control) and the opiate antagonist, naloxone (100 μg/hr) before and during acute moderate hemorrhage (15 ml/kg over 10 min). Infusion of naloxone before hemorrhage raised plasma ACTH and resulted in a significant increase in cortisol responses to hemorrhage control infusion. In contrast, ACTH and cortisol responses to hemorrhage tended to be blunted by central naloxone infusion. The responses of vasopressin, aldosterone and the catecholamines remained unaffected by naloxone. The fall in blood pressure and the rise in heart rate accompanying hemorrhage were likewise unaltered. These results suggest that brain opioid peptides have an inhibitory effect on basal ACTH secretion but do not play a major role in modulating the hemodynamic or pituitary-adrenal responses to acute moderate hemorrhage in conscious sheep. Numerous studies have established that the brain opioid system is activated by a variety of acute stressors, including hemorrhage (1) and other forms of shock and trauma (2, 3). These same stresses are potent stimuli to ACTH secretion. Several lines of evidence indicate that enkephalins and endorphins may participate directly in the regulation of ACTH secretion. The enkephalin agonist, DAMME, inhibits ACTH in sheep (4) and humans (5), opioid peptides suppress corticotropin-releasing factor (CRF) in vitro (6), and the opiate antagonist naloxone enhances ACTH secretion (7), including the ACTH response to exogenous CRF (8). These findings suggest that the brain opioid system may act to restrain both CRF release and ACTH responsiveness during acute stress. Using conscious sheep with indwelling cannulae in a lateral ventricle, we have examined the effect of central naloxone on the ACTH and neuroendocrine response to acute moderate hemorrhage. Since cardio-depressant effects of brain opioid activation also occur during hemorrhage (2, 9) apparently contributing to the shock syndrome, the hemodynamic response to acute, moderate hemorrhage during central administration of naloxone was also studied.

Arginine vasopressin (AVP) and AVP-like immunoreactivity in peripheral tissues.

Introduction THE NONAPEPTIDE arginine vasopressin (AVP) is classically synthesized as part of a precursor hormone [AVP-neurophysin II, (AVP-NPII)] in the magnocellular neurons of the supraoptic and paraventricular nuclei of the hypothalamus. It is then transported via their axons to the posterior pituitary, where it is secreted into the circulation (1). AVP, which has both antidiuretic and pressor effects, regulates water clearance in the kidney as well as blood pressure. In addition, AVP, together with CRF, has been shown to be involved in the regulation of ACTH secretion from the anterior pituitary (2–5). Furthermore, AVP has also been implicated in learning and memory (6, 7), central cardiovascular regulation (8–11), and other central nervous system functions (7, 12–14). Recently, the presence of many neuropeptides, including AVP, has been demonstrated in a number of peripheral, mainly endocrine tissues, largely on immunochemical criteria. Thus, this review is concerned with the demonstration of immuno...

Immunoneutralization of oxytocin attenuates stress-induced corticotropin secretion in the rat

Recent studies have demonstrated that oxytocin (OT) is released during certain stresses and that OT can potentiate the activity of CRF in vitro. To better define the role of OT during stress, the effect of injections of anti-OT antiserum on stress-induced corticotropin (ACTH) secretion was studied in vivo. A dose of antiserum which completely neutralized the increase in plasma OT levels during tail-hang stress caused a 59% decrease in plasma ACTH concentrations ( P < 0.005). The data support a physiologic role for OT in the regulation of ACTH secretion.

Evidence against a short feedback in the regulation of ACTH secretion in man

Journal Article Evidence against a short feedback in the regulation of ACTH secretion in man Get access U Deuss, U Deuss Medizinische Universitätsklinik II KölnNeurochirurgische Universitätsklinik Köln Search for other works by this author on: Oxford Academic Google Scholar D Kaulen, D Kaulen Medizinische Universitätsklinik II KölnNeurochirurgische Universitätsklinik Köln Search for other works by this author on: Oxford Academic Google Scholar D Kallabis, D Kallabis Medizinische Universitätsklinik II KölnNeurochirurgische Universitätsklinik Köln Search for other works by this author on: Oxford Academic Google Scholar E Hamel E Hamel Medizinische Universitätsklinik II KölnNeurochirurgische Universitätsklinik Köln Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 110, Issue 1_Supplement_a, Apr 1979, Page S176, https://doi.org/10.1530/acta.0.109S176 Published: 01 April 1985

Implication of the serotoninergic system in the decreased ACTH response to stress after lesion of the amygdaloid central nucleus

1. The present study was designed to ascertain the possible implication of the serotoninergic system and the central amygdaloid nucleus in the control of ACTH secretion in response to immobilization stress. 2. The response to immobilization stress of intact and lesioned animals was studied by monitoring the plasma and pituitary ACTH concentration and the activity of the serotoninergic system within specific hypothalamic and amygdaloid nuclei. 3. Bilateral lesions of the central nucleus of the amygdala significantly decreased the secretion of ACTH in response to immobilization. Moreover, the serotoninergic activity in most of the hypothalamic and in all the amygdaloid nuclei studied was greatly increased. A 60-min immobilization stress prevented this increase in the hypothalamic nuclei but not in the amygdala. 4. These results indicate that the central nucleus of the amygdala participates in the regulation of ACTH secretion in response to immobilization stress. Furthermore, they substantiate the hypothesis of a participation of the serotoninergic system in limbic areas, particularly in nuclei which contain neurons possessing glucocorticoid receptors such as the medial, basomedial and cortical amygdaloid nuclei.

Corticotropin-Releasing Activity of the Renin-Angiotensin System Peptides in Rat and in Man

In this study we investigated in the rat the binding and corticotropin-releasing factor (CRF) activity of various constituents of the renin-angiotensin system and the possible angiotensin II receptor changes following procedures known to alter plasma renin activity. We investigated also the CRF activity of angiotensin II in vitro and in vivo in humans. The CRF activity of peptides was studied by their ability to stimulate ACTH release from pituitary cells. Deleting amino acids from the N-terminus of angiotensin II resulted in decreased CRF activity; while the ED50 for angiotensin II was 2 nM, it increased to about 10 nM for the (2-8)-heptapeptide. Angiotensin I had a weak CRF activity, whereas the substrate angiotensinogen had no stimulatory effect even at a concentration of 100 nM. There was a strong correlation between the activation and binding properties of all peptides tested. Dietary salt load or depletion as well as dexamethasone treatment did not affect the number nor the affinity of pituitary angiotensin II receptors. Angiotensin II had a CRF activity on human pituitary cells in vitro. However, peripherally injected agiotensin II at a pressive dose of 7 ng/kg/min did not produce any ACTH release in normal male volunteers. These data suggest that angiotensin II may play a modulatory role in the physiological regulation of ACTH secretion, but this role might be attributed to the endogenous brain angiotensin II as it is not closely dependent on the angiotensin II plasma levels.

Clinical and experimental studies in the role of GABA in the regulation of ACTH secretion

Experimental studies in animals and man suggest that there is tonic inhibitory GABA-ergic control of corticotrophin (ACTH) secretion. Treatment with sodium valproate (which potentiates the action of GABA postsynaptically) reduces the gross hypersecretion of ACTH seen in patients suffering from Nelson's syndrome, whilst having no direct effect on pituitary tumour tissue incubated in vitro . It is likely that the drug exerts its effects at the hypothalamic level as treatment of rats with sodium valproate impairs the secretion of corticotrophin-releasing factor (CRF). It is possible that Nelson's syndrome is a neuroendocrine disease caused by a deficiency in the hypothalamic GABA-ergic system.

Oxytocin potentiates the ACTH-releasing activity of CRF(41) but not vasopressin

The effects of CRF(41), oxytocin (OT), and arginine vasopressin (AVP) on ACTH secretion were studied alone and in combination in an in vitro system of superfused rat hemipituitaries. CRF(41) (10 −9M) and AVP (10 −8M) alone produced a significant increase in ACTH secretion while OT (10 −8M) alone had no effect. However the same concentration of OT markedly potentiated the ACTH response to CRF(41) while having no effect on the ACTH response to AVP. The data support a physiologic role for OT in the regulation of ACTH secretion.

Clinical and experimental studies on the role of GABA in the regulation of acth secretion: a review

Clinical and experimental studies on the role of GABA in the regulation of acth secretion: a review

Intravenous injections of nicotine induce very rapid and discrete reductions of hypothalamic catecholamine levels associated with increases of ACTH, vasopressin and prolactin secretion.

The present findings show that nicotine given i.v. can within minutes induce increases of ACTH, vasopressin and prolactin secretion in the male rat, giving further evidence for the existence of nicotine-like cholinergic receptors involved in the regulation of these hormones. These changes were associated with rapid reductions of NA levels in the subependymal layer of the median eminence, in the nuc, dorsomedialis hypothalami and in the anterior and posterior periventricular hypothalamic area as revealed by quantitative microfluorimetrical measurements of CA fluorescence. Intraindividual correlations indicate the involvement of an inhibitory noradrenergic mechanism in the subependymal layer of the median eminence in the regulation of ACTH secretion, the involvement of noradrenergic mechanisms in the posterior periventricular area in the regulation of prolactin secretion and the involvement of dopaminergic mechanisms in the medial palisade zone of the median eminence in the regulation of prolactin secretion. A rapid rise of prolactin secretion seems to be associated mainly with a reduction of NA levels in the posterior periventricular area indicating the existence of a possible facilitatory noradrenergic mechanism in this region regulating prolactin secretion.

Evidence of Vasopressin in Adenohypophysis: Research into Its Role in Corticotrope Activity

The presence of vasopressin (VP) in pars distalis of rats and pigs was investigated. Using radioimmunoassay and bioassay of VP, a substance with immunological and biological properties of this hormone was found. This substance was not detected in the adenohypophysis of rats with diabetes insipidus. A partial purification of the VP-like peptide showed that it had the chromatographic and electrophoretic properties of VP. It could be identified with arginine vasopressin (AVP) in the case of the rat and lysine-vasopressin (LVP) in the case of the pig. In the Wistar strain, adrenalectomy induced progressively increasing concentrations of adenohypophysial VP. This increase was significant 15 days after surgery. It could be prevented by treatment with dexamethasone. These results indicate that the presence of VP in the anterior pituitary is related to the regulation of ACTH secretion.

INHIBITION AND FACILITATION OF FEEDBACK INFLUENCES OF DEXAMETHASONE ON ADRENOCORTICAL RESPONSES TO ETHER STRESS IN RATS WITH HYPOTHALAMIC DEAFFERENTATIONS AND BRAIN LESIONS

In order to elucidate the mechanisms and the sites of action of the negative feedback of corticoids in the regulation of ACTH secretion, the effects of systemically administered dexamethasone on adrenocortical responses to ether stress were studied in intact rats and in 11 experimental groups. These included animals with partial anterior, anterolateral, posterolateral, posterior and small posterior deafferentations as well as bilateral lesions in the medial forebrain bundle (MFB), fasciculus longitudinalis dorsalis (FLD), medial and lateral midbrain reticular formation (MRF) and in the ventrolateral pons. In rats with posterior hypothalamic deafferentation the degree of the inhibitory effect of dexamethasone was much smaller than that in intact animals. In animals with lesions in the FLD and MRF, dexamethasone also produced a reduction in the suppression of the response, though the difference was not significant. Bilateral lesions in the MFB and MP have on the other hand very significantly enhanced the effect of the negative feedback of dexamethasone when compared to intact rats. These data would indicate that hypothalamic deafferentations and brain lesions may change the sensitivity of the hypothalamus for the feedback control of corticoids and that there exist two antagonistic systems, an inhibitory and a facilitatory, in the brain which mediate this effect.

Feedback effects of dexamethasone on adrenocortical responses in rats with fornix section.

To investigate the sites of the negative feedback of corticoids in the regulation of ACTH secretion, the effect of 10 mug of dexamethasone on adrenocortical responses to ether stress was studied in intact and fornix-sectioned rats. Dexamethasone pretreatment in both groups depressed significantly both the basal and stress plasma corticosterone levels. However, in rats with fornix section the amount of depression of the adrenocortical response was much smaller than in intact animals, when compared to the non-treated group. These data would inicate that extrahypothalamic regions play a role in the action of glucocorticoids in the feedback control of pituitary-adrenal function and that the hippocampus participates in this mechaism.

Effect of cortisol on the excitability of limbic structures of the brain in freely moving rats

The effects of cortisol on the excitability of the dorsal hippocampus, septum, hypothalamus and the pontine reticular formation in unrestrained, unanesthetized rats with permanently-implanted electrodes were investigated. The hormone produced a slowing in the spontaneous activity in these regions. The stimulation of the septum, hypothalamus and reticular formation had no appreciable influence on the local or propagated electrical activity of the brain after cortisol injection; however in 14 out of 29 experiments hippocampal stimulation with the same voltages as before cortisol administration, induced generalized convulsive activity. The attacks consisted of high-voltage spikes and slow-wave activity and were followed by a post-seizure exhaustion in the hippocampus. In half of the rats behavioral convulsions also appeared. The convulsive effects of cortisol on the brain are briefly reviewed and the specificity of hippocampal involvement in the present experiments is emphasized. The possible significance of the present findings in relation to the feedback of glucocorticoids on the brain, in the regulation of ACTH secretion, is discussed. The experiments described may also contribute to our understanding of the mechanisms of the convulsive effects of cortisol on the brain.

Inhibition of firing is the primary effect of microelectrophoresis phoresis of cortisol to units in th rat tuberal hypothalamus

The effects of microelectrophoresis of cortisol on the firing of single cells in the tuberal hypothalamus of the rat were studied with the aid of multibarrel microelectrodes. It should be noted that the electrodes used were particularly fine (1–2 μm overall diameter) allowing close approach to cells without damaging them, as well as permitting the use of small driving currents to obtain the reported effects. Both spontaneously active and ‘silent’ units activated by glutamate were investigated. Approximately half of the units reacted to the application of the hormone, and more than 80% of the responsive cells showed reduction in the rate of firing. Units with slower spontaneous firing rates were more liable to respond to cortisol than those with faster rates and were more liable to show an inhibitory response. ‘Fast’ cells were more dorsally located than ‘silent’ cells and non-responsive slow cells were more dorsally located than either cortisol-inhibited or -accelerated slow cells. The direction of the response did not depend on the glutamate adjusted background rate of firing. These results were not dependent on the presence of glutamate in the microelectrode nor did the application of chloride or succinate ions mimic the effects of cortisol. The literature dealing with the effects of glucocorticoids on single cell activity in the hypothalamus is summarized and it is suggested that the demonstrated electrophysiological findings may be related to the negative feedback at the hypothalamic level exerted by the glucocorticoids in the regulation of ACTH secretion.

Changes in Plasma Corticosterone and Hypothalamic CRF Levels Following Intraventricular Injection or Drug-induced Changes of Brain Biogenic Amines in the Rat

In order to study the role of brain biogenicamines in the regulation of ACTH secretion under basal and stress conditions, we examined changes in plasma corticosterone and hypothalamic CRF levels in ma

Effect of dexamethasone on adrenocortical responses in intact and hypothalamic deafferented rats.

ABSTRACT The effects of systemically administered dexamethasone on adrenocortical responses to ether stress were studied in intact and in hypothalamic deafferented rats, in which a hypothalamic island was produced. The inhibitory effect of dexamethasone was twice as marked in the intact animals than in the rats with hypothalamic islands. However, direct implantation of dexamethasone into the mediobasal hypothalamus depressed the adrenocortical responses to the same extent in the intact and the deafferented rats. These results would indicate that the negative feedback of dexamethasone in the regulation of ACTH secretion is exerted at hypothalamic levels and that other extra-hypothalamic structures also participate in this mechanism.

Circulating Adrenocorticotropin (ACTH) as a Controlled Variable in the Regulation of ACTH Secretion

Rats received 21 daily injections of hydrocortisone acetate, beginning 5 days after bilateral adrenalectomy. Immediately following cessation of hydrocortisone administration, adenohypo-physial adrenocorticotropin (ACTH) concentration was reduced to about 40% of intact, control levels and remained at this low level for 16 days. There followed a gradual increase to intact control levels by 32 days, to 150% of control by 48 days, and to 170% of control by 64 days. The daily administration of a long-acting ACTH preparation following the cessation of hydrocortisone administration altered this response. Adenohypophysial ACTH levels remained lower than in the animals not receiving ACTH, reaching only 50% of control at 32 days and 93% of control at 48 days. At 64 days, ACTH concentration was actually higher in the ACTH-treated group, reaching over 300% of control values. These findings demonstrate (a) that the circulating level of ACTH can, in itself, alter adenohypophysial ACTH concentration, and (b) the importance of timed studies, since, depending on the time chosen, ACTH administration will depress, augment, or indeed produce no change in adenohypophysial ACTH concentration. We conclude that the circulating levels of ACTH can alter ACTH secretion.

Effects of cortisol on unit activity in the hypothalamus of the rat

The effects of cortisol on the spontaneous activity of single cells and their responsiveness to sensory stimuli were studied in the anterior-tuberal and posterior hypothalamus in rats under urethane anesthesia and compared to nontreated animals. It was found that the hormone increased the average rate of spontaneous firing both in the anterior-tuberal and posterior hypothalamus. While in the nontreated rats the sensory stimuli caused a predominant increase in cell firing in the anterior-tuberal hypothalamus, in the cortisol-treated rats there was an average decrease in unit discharge. On the other hand in the posterior hypothalamus in treated animals the sensory stimuli produced an increase in the average rate of firing. When the effects of the hormone were evaluated in the total population of cells by determining changes in the coefficient of variation and the proportion of the time intervals within the main mode in the time-interval histogram, it was found that the hormone modified the spontaneous activity and the responsiveness of anterior but not of the posterior hypothalamic neurones when compared to nontreated animals. The possible relations of these electrophysiological findings to the negative feedback exerted by the adrenocortical hormones at hypothalamic levels, in the regulation of ACTH secretion, are discussed.

Effects of alpha methyl tyrosine and p-chlorophenylalanine on the regulation of ACTH secretion.

The effect of α-methyl tyrosine or p-chlorophenylalanine pre-treatment of rats was tested on the ability to respond to anacute stress, a chronic stress, and to reserpine-induced ACTH hypersecretion. This pretreatment had no effect on any of these pituitary responses or on the depletion of CRF that accompanies the administration of reserpine.