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PubMed1986

By 95 days of gestation CRF increases plasma ACTH and cortisol in ovine fetuses.

Plasma adrenocorticotropin (ACTH) and cortisol (F) responses to 15-min intravenous infusions of synthetic ovine corticotropin-releasing factor (CRF) were measured by radioimmunoassay in three groups of chronically cannulated ovine fetuses. Fetuses (n = 7) in group I were 107 +/- 2 days gestation (0.72 G) and fetuses (n = 7) in group II were 126 +/- 2 days gestation (0.86 G). Group III fetuses (n = 5) were studied at 5-day intervals during the last 2 wk of gestation. Resting fetal plasma ACTH levels were not significantly different among the three experimental groups. Infusions of CRF (50 ng X kg-1 X min-1) provided similar, significant increases in fetal plasma ACTH concentrations in the three groups. In the young fetuses (group I) the ACTH responses to 500 ng X kg-1 X min-1 infusions of CRF were greater than responses to 50 ng X kg-1 X min-1 infusions P less than 0.001. In group II both doses of CRF produced equivalent increases in ACTH that were comparable with the responses to 50 ng X kg-1 X min-1 infusions in Group I. This suggests that fetal ACTH responsiveness to large doses of CRF decreases between 0.72 and 0.86 G. Resting fetal plasma F levels increased during gestation (P less than 0.01). There was an F response (P less than 0.001) to CRF in all groups with greater responses observed in the older fetuses. This suggests that fetal adrenal responsiveness to ACTH or other peptides released by CRF increases during gestation.

Adrenocorticotropic Hormone↗

PubMed1986

Role of vasopressin in stimulation of ACTH secretion by angiotensin II in conscious dogs.

Three series of experiments were performed in conscious dogs to test the possibility that the stimulation of adrenocorticotropin (ACTH) release by angiotensin II (ANG II) is mediated by arginine vasopressin (AVP). In the first protocol, the effect of ANG II on ACTH release was studied in dogs in which endogenous AVP levels had been increased by water deprivation. Water deprivation for 24 h increased plasma AVP concentration from 3.0 +/- 0.5 to 7.7 +/- 0.5 pg/ml (P less than 0.01) and increased the AVP response to the highest dose of ANG II (20 ng X kg-1 X min-1). Despite these changes, water deprivation failed to increase the ACTH response to ANG II. Next, the contribution of endogenous AVP to the stimulation of ACTH release by ANG II was examined using the V1-receptor antagonist, d(CH2)5Tyr[Met]-AVP (10 micrograms/kg iv). The ACTH response to ANG II in the presence of the AVP antagonist (66.4 +/- 3.1 to 100.1 +/- 15.9 pg/ml) was not significantly less than that in its absence (53.0 +/- 4.8 to 72.2 +/- 11.1 pg/ml). Finally, ANG II and AVP were infused in combination to determine whether there is a synergism between these two peptides in the release of ACTH. In one protocol, AVP and ANG II were infused separately and in combination. The ACTH response to ANG II and AVP in combination (48.7 +/- 6.5 to 61.5 +/- 8.5 pg/ml) was not enhanced compared with the responses to ANG II (59.8 +/- 7.3 to 71.0 +/- 10.1 pg/ml) or AVP (48.8 +/- 5.7 to 55.6 +/- 6.5 pg/ml) alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1991

Chloride channel blockers inhibit ACTH secretion from mouse pituitary tumor cells.

The effect of several chemically related chloride channel blocking drugs was investigated on the adrenocorticotropic hormone (ACTH) secretory process in mouse clonal AtT-20 corticotrophs. When cells were simultaneously exposed to diphenylamine-2-carboxylate (DPC) or related substances (Hoechst compounds 131, 143, and 144) and the adenylate cyclase activator forskolin, ACTH secretion was inhibited by 76-95% [half-maximal inhibitory concentration (IC50) 450, 15, 84, and 32 microM, respectively]. All four compounds also blocked forskolin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) synthesis in AtT-20 cells by 51-87% (IC50 190, 29, 100, and 130 microM for DPC and compounds 131, 143, and 144, respectively). Pertussis toxin pretreatment of cells caused a partial reversal of DPC-inhibited forskolin-stimulated cAMP formation. The toxin had no effect on inhibition of forskolin-stimulated ACTH secretion by DPC. Secretion of ACTH in response to cAMP-independent stimulants such as the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate or the calcium channel agonist BAY K 8644 were blocked by compound 131 as was the secretory response to 8-bromoadenosine 3',5'-cyclic monophosphate. These results suggest that phenylanthranilic acids have adenylate cyclase inhibiting action but that the postcyclase activity is more relevant to the ability of these compounds to block ACTH secretion. DPC also blocked 125I efflux (an index of Cl- secretion) from AtT-20 cells. Because an increase in osmotic strength of the culture media reduced forskolin-stimulated ACTH secretion, these data suggest that DPC and related compounds may negatively modulate chloride-dependent osmotically driven ACTH secretion from AtT-20 cells.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1986

Interaction between CRF and angiotensin II in control of ACTH and adrenal steroids.

These experiments were designed to test for interactions between plasma angiotensin II (ANG II) and corticotropin-releasing factor (CRF) in the control of plasma adrenocorticotropin (ACTH), aldosterone, and corticosteroids, mean arterial pressure (MAP), and heart rate (HR) in conscious dogs. Five trained dogs with exteriorized carotid arteries were studied. Each dog was infused with saline and with CRF at three rates (2.5, 5, and 10 ng X kg-1 X min-1) and ANG II at three rates (5, 10, and 20 ng X kg-1 X min-1) for 60 min. The same animals were also coinfused with 10 ng X kg-1 X min-1 ANG II at each rate of CRF infusion and with 10 ng CRF X kg-1 X min-1 at each rate of ANG II infusion. Infusion of ANG II alone caused dose-related increases in aldosterone, corticosteroids, and MAP but did not alter ACTH or HR. Infusion of CRF alone increased ACTH, aldosterone, and corticosteroids but not MAP or HR. Coinfusion of CRF and ANG II caused ANG II dose-related ACTH responses but did not alter the sensitivity of the ACTH responses to CRF. Thus it appears that ANG II alone does not stimulate ACTH release but requires increased CRF concentrations to effect ACTH release.

Adrenal Cortex Hormones↗

PubMed1986

Medullary lesions eliminate ACTH responses to hypotensive hemorrhage.

The adrenocorticotropin (ACTH) response to hemorrhage (15 ml . kg-1 . 3 min-1) before and 30 min or 4 days after placement of bilateral electrolytic lesions of the nucleus tractus solitarius (NTS) were examined in anesthetized and in conscious rats. Two groups of rats were anesthetized with pentobarbital sodium (45 mg/kg). Femoral arterial and venous cannulas were placed acutely in the anesthetized group and chronically in the conscious group. Each rat received a hemorrhage 30 min before and 30 min after NTS lesions (in the anesthetized group) and 1 day before and 4 days after NTS lesions (in the conscious group). Plasma ACTH was determined before and 20 min after hemorrhage, and mean arterial blood pressure and heart rate were measured throughout. The baroreceptor reflex (bradycardia caused by a phenylephrine-induced rise in MABP) was determined 5 min before hemorrhage (in the anesthetized group) and 1 day before hemorrhage (in the conscious group) to assess the effectiveness of lesion. Hexamethonium was given to rats that developed hypertension postlesion and to sham-lesioned controls. Plasma ACTH did not increase after hemorrhage 30 min or 4 days after NTS lesions when compared with the other groups (sham, sham with hexamethonium, and missed lesion) and to prelesion controls. Also, lesions of the NTS had no effect on resting ACTH levels 4 days later. Mean arterial pressure and heart rate decreased during hemorrhage to similar extents before and after lesions in all groups. This study demonstrates that lesions of the NTS eliminate the ACTH response to hemorrhage immediately and 4 days after the lesions but have no effect on resting ACTH levels. The result suggests that the NTS is an essential part of the neural pathway for ACTH release after hemorrhage.

Adrenocorticotropic Hormone↗

PubMed1988

Evidence for rapid inhibition of ACTH by corticosteroids in dogs.

These experiments were designed to determine whether stimulated adrenocorticotropic hormone (ACTH) secretion in dogs can be rapidly inhibited by increases in plasma corticosteroid concentrations. Five dogs were injected with a 2:1 mixture of cortisol to corticosterone (corticosteroids; total doses of 22.5, 45, or 90 micrograms/kg) or vehicle simultaneously with the injection of insulin (0.5 U/kg). These dogs were also injected with corticosteroids (45 micrograms/kg) with ovine corticotropin-releasing factor (oCRF-41; 1 micrograms/kg) or with the same dose of corticosteroids alone. Plasma ACTH and corticosteroid concentrations were measured for 90 min after the injections. The inhibition of ACTH secretion was significant 10 min after injection of oCRF-41 and 40 min after injection of insulin. The first significant increase in ACTH during insulin-induced hypoglycemia does not occur until 30 min, however. Therefore, after both of these stimuli to ACTH, the ACTH response is inhibited within approximately 10 min of its onset. The results suggest that canine ACTH responses to stimuli can be rapidly inhibited and that one site of this inhibition is the pituitary.

Adrenocorticotropic Hormone↗

PubMed1988

Control of sodium excretion in NE-ACTH hypertension: role of pressure natriuresis.

The purpose of this study was to test the hypothesis that, in the presence of high circulating catecholamines, ACTH decreases renal excretory capability and that its natriuretic effects are caused by increased renal arterial pressure (RAP). In six conscious dogs, norepinephrine (NE, 0.4 micrograms.kg-1.min-1) alone for 5 days caused a small but significant rise in arterial pressure (AP) from 102 +/- 6 to 115 +/- 8 mmHg. An infusion of ACTH (600 micrograms/day) for 7 days, superimposed upon the NE, caused a further rise in AP to a plateau of 143 +/- 9 mmHg after 5 days while cumulative sodium balance fell to -149 +/- 41 meq by the 7th day. Cumulative water balance fell to -660 +/- 232 ml by the 3rd day and then increased slightly. In contrast, when ACTH infusion was repeated during NE infusion while RAP was prevented from increasing using a servo-controlled aortic occluder, cumulative sodium balance increased to 197 +/- 35 meq and AP rose from 108 +/- 5 to 168 +/- 5 mmHg after 7 days and did not plateau. Cumulative water balance rose to 2,325 +/- 445 ml. Thus, in dogs receiving a background infusion of NE, ACTH causes moderate hypertension and natriuresis. However, when RAP is not allowed to rise, ACTH is associated with sodium retention and severe systemic hypertension, suggesting that the natriuretic effects of ACTH are caused by increased RAP and that the natriuresis blunts the chronic hypertensive effects of ACTH.

Adrenocorticotropic Hormone↗

PubMed1989

Vasopressin and ANG II in the control of ACTH secretion and arterial and atrial pressures.

Hypotension stimulates the secretion of adrenocorticotropin (ACTH) and vasopressin (AVP) and increases plasma levels of angiotensin II (ANG II). Because AVP and ANG II increase ACTH secretion, the present experiments were performed to evaluate the role of these peptides in the increases in plasma ACTH and glucocorticoid concentrations produced by hypotension in conscious dogs. This was accomplished by determining whether administration of receptor antagonists to vasopressin, [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine]Arg8-vasopressin, and ANG II (saralasin), reduced the ACTH and glucocorticoid responses to infusion of four doses of the vasodilator nitroprusside. Nitroprusside (NP) infusion produced dose-dependent decreases in mean arterial pressure. Larger decreases in arterial pressure were produced in dogs pretreated with the AVP antagonist or with both saralasin and the vasopressin antagonist. Left and right atrial pressures also fell with NP infusion, and larger decreases in atrial pressures were found in dogs pretreated with the AVP antagonist. Finally, NP infusion increased plasma glucocorticoid concentration and plasma ACTH concentration. Both the glucocorticoid and the ACTH responses to hypotension were reduced in dogs given the AVP antagonist and in dogs given both saralasin and the AVP antagonist, but there was no difference in the effect of AVP blockade alone vs. the effect of combined AVP and ANG II blockade. These data suggest that AVP, but not ANG II, is required for normal glucocorticoid and ACTH responses to hypotension. They also suggest that AVP is necessary for normal maintenance of arterial blood pressure and atrial pressures during NP infusion.

Adrenocorticotropic Hormone↗

PubMed1994

Lesions of hypothalamic PVN partially attenuate stimulatory action of alcohol on ACTH secretion in rats.

We have previously shown that the ability of alcohol to stimulate adrenocorticotropic hormone (ACTH) secretion was significantly blunted by immunoneutralization of endogenous corticotropin-releasing factor (CRF) and that long-term exposure to alcohol increased CRF mRNA levels in the paraventricular nucleus (PVN) of the hypothalamus. In the present study, we further investigated the participating role of the PVN by studying the effect of bilateral lesions of the PVN on alcohol-induced ACTH release. The acute injection of alcohol (1.5 g/kg ip) induced significant increases in plasma ACTH levels in sham-operated animals. Lesions of the PVN attenuated this response but did not abolish it. Indeed, lesioned rats retained significantly elevated ACTH values despite removal of secretagogues of PVN origin. Because removal of hypothalamic CRF can alter ACTH secretion in response to secretagogues, we studied possible changes in pituitary responsiveness to CRF. The results failed to indicate that hyperresponsiveness of the corticotrophs played a major role in accounting for the residual ACTH release of lesioned rats after alcohol treatment. We conclude that brain regions other than the PVN can modulate ACTH release during acute administration of alcohol.

Adrenocorticotropic Hormone↗

PubMed1996

Inhibition of stimulated and basal ACTH by cortisol during ovine pregnancy.

In pregnant ewes, as in pregnant women, plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations are increased. Inhibition of free cortisol concentrations by dexamethasone, a synthetic glucocorticoid, is reduced in pregnant women compared with nonpregnant women. These experiments were designed to test the hypothesis that basal and stimulated ACTH concentrations are less sensitive to negative feedback inhibition by cortisol in pregnant ewes than in nonpregnant ewes. Ewes were infused with vehicle and with cortisol at two different rates (1 and 2 micrograms.kg-1.min-1) for 1 h; plasma ACTH concentrations during and after the infusion and after subsequent stimulation by hypotension were measured. Basal plasma ACTH concentrations during a 2-h infusion of cortisol (2 micrograms.kg-1.min-1) were also measured in undisturbed ewes. Cortisol significantly inhibited both stimulated and basal ACTH. The degree of suppression of ACTH was not reduced in the pregnant ewes compared with the nonpregnant ewes. The results indicate that both basal and stimulated ACTH are sensitive to negative feedback inhibition by cortisol during ovine pregnancy.

Adrenocorticotropic Hormone↗

PubMed1978

In vitro regulation of ACTH release from neurointermediate lobe of rat hypophysis. I. Effect of crude hypothalamic extracts.

Using incubated glands, we showed that cerebral cortex and liver extracts (CCE and LE) stimulated ACTH release from neurointermediate lobe (NIL) of hypophysis as well as hypothalmus extract (HE) did. Moreover, the HE-induced ACTH release was much smaller for the NIL (1.9 X basal level) than for the anterior lobe (AL; 13.7 x basal level). Thus, under these conditions, HE seemed to have no specific effect on NIL ACTH release. Using superfused glands, we showed: (a) that both spontaneous and HE-induced ACTH release decreased during superfusion; (b) that using this system, a specific stimulatory effect on HE on NIL was observed. In contrast to HE, CCE and LE had only a small effect on NIL ACTH release (always less than 20% of that caused by HE) which could be considered as a nonspecific response; (c) that trypsin suppressed the stimulating effect on HE as well on NIL as on AL; and (d) that arginine antidiuretic hormone (ADH) was not responsible for the stimulating effect of HE on NIL ACTH release, because synthetic ADH had no effect and HE containing ADH (from normal rats) or HE containing no ADH (from Brattleboro rats or from immunoneutralization of ADH in normal HE) had the same effect. From these results, we can conclude that HE contain a peptidic factor different from ADH which is able to stimulate in vitro release of ACTH from the NIL.

Adrenocorticotropic Hormone↗

PubMed1981

Vasopressin and CRF-ACTH in adrenalectomized and dexamethasone-treated rats.

Median eminence corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) and pituitary and peripheral plasma adrenocorticotropin (ACTH) and AVP were measured in male Wistar rats 1 and 2 weeks after bilateral adrenalectomy (ADX), sham operation (SHAM) or dexamethasone-treatment (DEX). Median eminence AVP content was unchanged 1 week after ADX but was significantly elevated 2 weeks after ADX, whereas CRF activity was reduced at 1 week after ADX and returned to control range at 2 weeks. Anterior pituitary ACTH content was elevated but posterior pituitary AVP content was reduced at 1 and 2 weeks after ADX. Plasma ACTH was greatly elevated in ADX rats and reduced in DEX rats, whereas plasma AVP did not differ significantly between these two groups or the control group. When ADX and SHAM rats were laparotomized under ether, plasma ACTH increased greatly, but this elevation was prevented by DEX treatment. The plasma AVP level was elevated in all three groups 2.5 min after onset of stress but returned to the basal range at 20 min. Median eminence CRF and AVP and pituitary ACTH and AVP were not significantly changed after onset of stress. These results indicate that the vasopressin and CRF-ACTH responses were not consistent in the median eminence, pituitary and peripheral plasma and suggest that vasopression is not involved in the feedback and acute stress mechanism of CRF-ACTH secretion. However, we have to measure CRF activity and AVP concentration in the hypophysial portal blood to confirm this conclusion.

Adrenalectomy↗

PubMed1985

ACTH and corticosterone secretion in rats following removal of the neurointermediate lobe of the pituitary gland.

Surgical removal of the neurointermediate lobe of the pituitary gland (NIL-X) in the rat resulted in two abnormalities in ACTH secretion: (1) plasma ACTH and corticosterone levels were elevated in the morning and over a 24-hour period compared with levels in control (NIL-C) rats, and (2) although NIL-X and NIL-C rats had acute increases in plasma ACTH and corticosterone of equal magnitude after interoceptive stimuli (hemorrhage, surgery), NIL-X rats demonstrated markedly smaller elevations in plasma levels of these hormones after neurotropic stimuli (noise, novel environment). This subnormal adrenocortical response of NIL-X rats was not due to an impairment in perception of a neurotropic stimulus; these rats had normal latencies to paw licking and to jumping off a heated surface, yet smaller increases in plasma corticosterone after the stimulus. The impairment in ACTH response was not related to stimulus intensity, as NIL-X and NIL-C rats had equal ACTH and corticosterone secretion during both low and high levels of insulin-induced hypoglycemia. NIL-X rats demonstrated a significant elevation in daily water intake, although hematocrit, plasma Na+, K+, osmolality and protein were normal. Significant diurnal rhythms in plasma corticosterone levels and in water intake were maintained as well. The elevated morning plasma ACTH levels, the blunted hormone increases after noise, and the increase in water intake persisted in NIL-X rats 2 months after surgery. These data indicate that removal of the NIL results in (1) chronic elevations in basal ACTH and corticosterone secretion, and (2) chronic impairment in adrenocortical responses to neurotropic stimuli, but not to interoceptive stimuli. The deficit is not due to impaired perceptual capacity nor to the intensity of the stimulus.

Adrenocorticotropic Hormone↗

PubMed1985

Calmodulin inhibitors decrease the CRF-and AVP-induced ACTH release in vitro: interaction of calcium-calmodulin and the cyclic AMP system.

The effect of N-(6-aminohexyl)-5-chloro-naphthalene-1-sulfomide (W-7) and trifluoperazine (TFP) was examined on ACTH release from cultured rat anterior pituitary cells and pituitary halves. These drugs significantly inhibited the ACTH release induced by synthetic ovine corticotropin-releasing factor (CRF) in a dose-related manner. In pituitary halves, arginine vasopressin (AVP) at 10 and 100 ng/ml showed almost the same ACTH-releasing activity as CRF at the same concentrations. W-7 and TFP inhibited the CRF-and AVP-induced ACTH release from pituitary halves. The cyclic AMP levels in the pituitary halves were significantly increased by CRF, but not AVP. Although W-7 inhibited CRF-induced ACTH release, it did not have an effect in cyclic AMP accumulation. These results suggest that CRF exerts ACTH-releasing activity through both the calcium-calmodulin system and cyclic AMP system and that AVP stimulates ACTH release mainly through the calcium-calmodulin system.

Adrenocorticotropic Hormone↗

PubMed1993

Factors from the paraventricular nucleus mediate inhibitory effect of alpha-2-adrenergic drugs on ACTH secretion.

The controversy about putative stimulatory and inhibitory functions of catecholamines in regulation of ACTH secretion has been recently shifted towards a consensus that during stress catecholamines stimulate corticotropin-releasing factor (CRF-41) containing neurons through alpha 1-adrenoreceptors, while inhibiting their own secretion acting on presynaptic alpha 2-receptors. In this study the effect of the alpha 2-agonist clonidine and the antagonist CH-38083 was studied on exogenous CRF-41/AVP-induced ACTH secretion in rats with/without paraventricular nucleus lesion. Clonidine (30 micrograms/kg) attenuated CRF-41/AVP (1 pmol/10 pmol)-induced ACTH secretion in sham-operated rats, but was ineffective in reducing CRF-41/AVP-induced ACTH secretion in rats with paraventricular nucleus lesion. In sham-operated rats, alpha 2-receptor antagonist CH-38083 slightly elevated the basal, and significantly potentiated the CRF-41/AVP-induced ACTH secretion, while it had no effect on the hypophyseotropic cocktail-induced ACTH response in paraventricular-lesioned rats. Neither the agonist nor the antagonist affected CRF-41/AVP-induced ACTH release from pituitary fragments in vitro. These results suggest that in response to activation of alpha 2-adrenoreceptors a corticotropin release-inhibiting substance is released from the paraventricular nucleus.

Adrenocorticotropic Hormone↗

PubMed1993

Effects of the glucocorticoid antagonist RU 486 on pituitary-adrenal function in patients with anorexia nervosa and healthy volunteers: enhancement of plasma ACTH and cortisol secretion in underweight patients.

To further explore whether the hypercortisolism of anorexia nervosa reflects an alteration in the set point for corticotropin-releasing hormone (CRH) secretion or is a manifestation of glucocorticoid resistance, we examined plasma ACTH and cortisol responses to the competitive glucocorticoid antagonist RU 486 (10 mg/kg, p.o. at 8.00 h) versus placebo (PBO) in 7 healthy female volunteers and 8 patients with DSM-III-R anorexia nervosa, all of whom were studied while underweight [64.3 +/- 2.1% average body weight (ABW), mean +/- SE] and 5 of whom were restudied longitudinally following refeeding (> or = 85% ABW, mean 87.4 +/- 0.4% ABW). Blood samples were obtained from 16.00 to 16.30 h and from 4.00 to 8.00 h following dosing. Underweight anorexics were significantly hypercortisolemic by 24 h urinary free cortisol excretion compared with controls (239 +/- 37 vs. 119 +/- 12 nmol/day, p < 0.01). Both controls and underweight anorexics had robust early morning (4.00-8.00 h) plasma cortisol responses to RU 486 (465 +/- 61 and 719 +/- 49 nmol/l) compared with PBO (370 +/- 52 and 451 +/- 31 nmol/l; p < 0.02 and p < 0.01, respectively). The underweight anorexics showed a significant mean early morning plasma ACTH response to RU compared with placebo (3.28 +/- 0.63 vs. 2.01 +/- 0.24 pmol/l, p < 0.05), while the controls showed a trend toward an increase in mean plasma ACTH after RU (3.11 +/- 0.36 pmol/l) compared with PBO (2.31 +/- 0.41 pmol/l, p < 0.13); plasma ACTH means were greater on the RU day than the placebo day at 20 of 25 sampling points (p < 0.001). However, the increment in ACTH on the RU day compared to the placebo day was greater in the underweight anorexics at the first 20 of 25 consecutive time points of the early morning sampling period (p < 0.001). Moreover, underweight anorexics showed a significant plasma ACTH and cortisol response to RU 486 at 16.00-16.30 h (8-8.5 h following administration), while the controls showed no significant response of plasma ACTH or cortisol at this time. When restudied following weight recovery, anorexic patients showed reductions in 24-hour urinary free cortisol excretion (to 191 +/- 40 nmol/day) which were no longer significantly elevated compared with control values.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗

PubMed1994

Systemically administered histamine H1 and H2 receptor antagonists do not block the ACTH response to bacterial lipopolysaccharide and interleukin-1.

The administration of lipopolysaccharide (LPS) results in the activation of the hypothalamic-pituitary-adrenal axis (HPAA). We recently reported that the participation and interaction of LPS-induced proinflammatory cytokines were obligatory for the stimulation of adrenocorticotropic hormone (ACTH) release by LPS. LPS and LPS-derived cytokines also stimulate the release of histamine (HA). HA is a known hypothalamic neurotransmitter and activates the HPAA. Therefore, to elucidate the role of HA in LPS- and cytokine-induced ACTH release, we evaluated the effects of several HA H1 and H2 receptor antagonists on the ACTH response to LPS, recombinant human interleukin-1 alpha (rhIL-1 alpha) and HA in mice. Although all 3 of the H1 receptor antagonists administered (mepyramine (MEP), diphenhydramine (DPH) or promethazine (PMZ) were able to block the 10-min ACTH response to HA, only PMZ (a less selective H1 receptor antagonist than MEP) was able to reduce the LPS- or rhIL-1 alpha-induced ACTH responses. Ranitidine, a powerful and selective H2 receptor antagonist, had little effect on the LPS- and rhIL-1 alpha-induced ACTH responses, while metiamide (MET), a much less potent first-generation H2 receptor antagonist, substantially diminished ACTH release. The greater effectiveness of PMZ, in contrast to MEP or DPH, probably relates to the ability of phenothiazine derivatives to inhibit non-HA-dependent pathways involved in the stimulation of the HPAA by cytokines; the same may be true of MET.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1986

Adrenocortical responsiveness to graded ACTH infusions in normal young and elderly human subjects.

The responses of plasma cortisol, aldosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) to graded ACTH infusions (from 50 mU/h to 1,000 mU/h) in elderly subjects were compared with those in young subjects. There were no significant differences between young and elderly subjects in terms of the levels of plasma cortisol during ACTH infusion. The increment in median serum cortisol increase observed in elderly subjects was also equal to that found in young subjects. Plasma aldosterone concentration showed a gradual increase in response to ACTH infusion in both young and elderly individuals. There was no significant difference between the response of young and aged subjects. Significant increases in serum DHEA in response to ACTH infusion were observed in both young and aged individuals, however, the median increase of serum DHEA (delta DHEA) in the elderly subjects was markedly lower than that in the young ones. Serum DHEA-S concentrations prior to ACTH infusion were significantly lower in the elderly subjects. With graded infusions of ACTH, plasma DHEA-S concentrations in young subjects tended to increase gradually, whereas there was no significant increase in plasma DHEA-S concentrations in the elderly. These results are indicative that the responses of adrenal androgens in elderly subjects to small, graded doses of ACTH infusion are preferentially impaired; however, the responses of cortisol and aldosterone are well maintained.

Adrenal Cortex Hormones↗