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PubMed1990

Effect of ACTH suppression on adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA in 4-aminopyrazolopyrimidine-treated rats.

4-Aminopyrazolopyrimidine (4-APP) treatments to rats for 3 days induced 2-fold increase of circulating ACTH and 11-fold increase of adrenal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA compared to NaCl-treated controls. This in vivo model was used to study the effect of the suppression of ACTH secretion on the adrenal HMG-CoA reductase mRNA level. Dexamethasone (Dex) administration to 4-APP-treated rats caused a rapid and parallel decline of the levels of plasma ACTH and adrenal HMG-CoA reductase mRNA to 50% within 2.5 h, whereas the free and esterified cholesterol content was increased 5 and 9.4 times respectively. These changes could be counteracted by the co-administration of ACTH with Dex. Aminoglutethimide (AG) administration to 4-APP-treated rats, which increased the adrenal esterified cholesterol content (7.5 times), decreased the HMG-CoA reductase mRNA level (44%), despite plasma ACTH level remaining elevated. Moreover, the participation of newly synthesized protein(s) in the lowering of adrenal HMG-CoA reductase mRNA level induced by ACTH suppression is suggested by the fact that cycloheximide (Cyclo), when co-administered with AG, completely blocked the decrease of HMG-CoA reductase mRNA level, despite the plasma ACTH level decreasing by 68% and the free and esterified cholesterol content increasing 3.9 and 12.3 times, compared to 4-APP-treated rats. Furthermore, the specificity of these effects was established by the fact that the beta-actin mRNA level was not affected by the administration of either Dex, AG, Cyclo, or AG + Cyclo to 4-APP-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine↗
PubMed1991

The protein kinase C content is increased in the nuclear fraction of rat adrenal zona glomerulosa following long-term ACTH administration.

It is well known that the adrenal zona glomerulosa is transformed to zona fasciculata-reticularis in rats exposed chronically to ACTH. This model was used to study the intracellular distribution of protein kinase C, which is known to be involved in differentiation processes. Under basal conditions, in zona glomerulosa, 70, 23, and 7% of the protein kinase C was located in the cytosol, membrane and nuclear fractions, respectively. At 30 min after ACTH administration to rats, the protein kinase C content remained unchanged in the nuclear fraction, whereas that of the cytosolic fraction was decreased to 43% while in the membranes it was increased to 48%. After 2 days of ACTH treatment, we observed a significant increase, up to 25%, of protein kinase C in the nuclear fraction, a decrease to 47% in the cytosol, whereas the membrane fraction content had returned to its basal value. The intracellular distribution of inner zones was 17% in nuclear fraction, 47% in cytosol and 36% in membranes. ACTH treatments did not change these proportions. The total protein kinase C content of ACTH-treated groups was not different than that of their respective controls, in zona glomerulosa and in inner zones respectively. The cytosolic protein kinase C formed complexes with detergent-treated nuclei; this association was saturable, and could be measured by the ability of the kinase to bind [3H]PDBu ([20(n)-3H]phorbol-12,13-dibutyrate). The number of nuclear 'acceptor sites' thus measured was calculated to be 5245 fmol/mg DNA in the zona glomerulosa; this did not change significantly following a 3-day administration of ACTH. Protein kinase C prepared from the adrenal inner zones also bound zona glomerulosa detergent-treated nuclei but occupied fewer sites than the protein kinase C from the zona glomerulosa. In conclusion, the effects of chronic ACTH treatment on rat adrenal zona glomerulosa could be mediated by an increased level of protein kinase C in the nuclear fraction and possibly through its binding to specific 'acceptor sites'.

Adrenocorticotropic Hormone↗
PubMed1994

Regulation of bovine adrenal cell corticotropin receptor mRNA levels by corticotropin (ACTH) and angiotensin-II (A-II).

Bovine adrenal fasciculata-reticularis cells (BAC) expressed at least four ACTH receptor (ACTH-R) mRNA transcripts, one major of 3.6 kb and three minor of 4.2, 1.8 and 1.3 kb. ACTH and A-II increased ACTH-R mRNA levels in a time- and dose-dependent manner. At maximal concentrations, ACTH caused a 2.7-fold increase in the level of the major transcript of 3.6 kb with an ED50 = 10(-11) M and A-II produced a 2.4-fold increase with an ED50 = 5 x 10(-8) M. Under our experimental conditions, the stimulatory effects of both hormones appeared to be due to post-transcriptional changes rather than to transcriptional regulation since the hormonal effects were also observed in actinomycin-treated cells. The results indicate that regulation of ACTH-R mRNA levels may be one mechanism by which ACTH and A-II regulate adrenocortical functions.

Adrenocorticotropic Hormone↗
PubMed1975

Effect of ascorbic acid on ACTH-induced cyclic AMP formation and steroidogenesis in isolated adrenal cells of vitamin E-deficient rats.

Isolated adrenal cells from Vitamin E-deficient and control rats were prepared by a trypsin digestion method. Cyclic adenosine 3',5'-monophosphate (cyclic AMP) formation was studied in response to adrenocorticotropin (ACTH) in the presence and absence of ascorbate by measuring the conversion of prelabeled adenosine 5'-triphosphate [14C]ATP to cyclic [14C]AMP. Ascorbate (0.5 mM) inhibited ACTH-induced cyclic [14C]AMP formation in adrenal cells isolated from Vitamin E-deficient rats but had no effect in the control cells. The inhibitory effect of ascorbate on ACTH-induced cyclic AMP formation in Vitamin E-deficient rats decreased as the concentration of ACTH increased. In Vitamin E-deficient rats ascorbate inhibited ACTH-induced cyclic [14C]AMP formation after 30 min of incubation. There was no further significant accumulation of cyclic [14C]AMP at 60 min or 120 min although in the absence of ascorbate cyclic [14C]AMP continued to be formed. The in vitro addition of alpha-tocopherol reduced the inhibition of ACTH-induced cyclic [14C]AMP formation by ascorbate in Vitamin E-deficient rats. These studies suggest that alpha-tocopherol and ascorbate may affect ACTH-induced cyclic AMP formation through interaction with the membrane-bound enzyme adenylate cyclase.

Adrenal Glands↗
PubMed1985

The relationship of endogenous ACTH levels to visual-attentional functioning in patients with congenital adrenal hyperplasia.

The within subject experimental approach of either doubling cortisone medication dose or withdrawing steroid treatment for 36 hr preceding behavioral testing was found to induce corresponding significantly elevated or suppressed plasma ACTH levels, as measured by radioimmunoassay, in six of eight adults diagnosed as having congenital adrenal hyperplasia (CAH). During the session characterized by elevated ACTH levels, the CAH patients exhibited significantly reduced median reaction times on the Sternberg Item Recognition Task. Their response pattern was suggestive of facilitated visual attentional functioning and/or overt motor response capacity rather than alteration of simple cognitive processing. Moreover, Sternberg performance was significantly correlated with endogenous ACTH levels but not with levels of plasma cortisol or cortisone replacement medication. This enhancement of performance paralleled a previous finding of improved performance on the Sternberg paradigm by normal adults following exogenous administration of ACTH 4-10 (Ward et al., 1979). Further analysis of the Sternberg performance suggests that other variables such as mineralocorticoid treatment, type of CAH impairment, and sex may act to moderate the degree of ACTH-related facilitation on this task. Performance on other visual and verbal attention and memory tasks, found earlier to be sensitive indices of exogenous administration of ACTH 4-10 and related fragments, was not significantly altered by manipulation of endogenous ACTH levels in these CAH patients.

Adolescent↗
PubMed1985

Development and regeneration of motor systems under the influence of ACTH peptides.

ACTH peptides exert quantitative and qualitative influences on the formation and maturation of motor units in developing and regenerating neuromuscular systems. ACTH 4-10, administered daily (10 micrograms/kg. s.c.) from the day of birth, accelerated the rate at which muscle strength developed in the immature rat, the effect of this peptide being most marked in animals 11-15 days old. A similar increase in grasping time occurred in ACTH 4-10 treated animals, indicating that the peptide affects neuronal maturation at a time in development when organization and maturation of the neuromuscular system is most active. The synthetic analogue of ACTH 4-9 (Org 2766), administered in the same dosage, had little effect on these parameters, indicating a differential sensitivity to these similar peptides. Elevated circulating titers of ACTH, whether exogenous (0.2 U ACTH 1-39 IP daily), or endogenous (adrenalectomy), stimulated the formation of more functional motor units, as indicated by increased amplitude of muscle action potentials and tetanic tension following nerve stimulation. ACTH appears to favor the recovery of high threshold, small-size motor units. Fine control of muscle function in peptide-treated animals is partially restored, as indicated by the return of stepwise recruitment to an extent not seen in the reinnervated, saline-treated controls.

Adrenocorticotropic Hormone↗
PubMed1988

Mode of ACTH antipyretic action.

The method of intestinal cooling was used to analyze the effect of centrally administered ACTH in microgram quantities on hypothalamic centers regulating activity of thermoregulatory outputs (cold thermogenesis--CT, peripheral vasomotor tone--PVMT, respiratory evaporative heat loss--REHL). ACTH, when injected into the supraoptic area of the anterior hypothalamus of normal rabbits, had no significant effect on body temperature control. Intrahypothalamic administration of ACTH during the early phase of the fever, induced by intravenous injection of exogenous pyrogen, evoked dissociation of temperature thresholds for cold and warm defence, shifting the threshold for induction of cold thermogenesis to lower central temperatures. The thermosensitivity of centers controlling cold thermogenesis was lowered and the maximal values of cold thermogenesis were depressed to about 30% of those in control rabbits. Central administration of ACTH in the late phase of the fever (120 min after IV injection of endotoxin) induced a smaller effect than in the early phase of the fever--the downward shift of the temperature threshold for cold thermogenesis was less evident and the thermosensitivity of the controller remained unchanged. The changes in activity of thermoregulatory centers that occurred after ACTH in febrile rabbits correspond to those observed in the late phase of the fever in ACTH-untreated rabbits. It is suggested therefore, that the presumed increase in ACTH production during fever might represent a negative feed-back mechanism contributing to the termination of the febrile state.

Adrenocorticotropic Hormone↗
PubMed1990

Role of calcium in the expression of ACTH-induced stretching, yawning and penile erection.

The effect of omega-conotoxin GVIA, a potent and selective inhibitor of N-type calcium channels and of the organic calcium channel inhibitors nimodipine, verapamil and flunarizine, on stretching, yawning and penile erection induced by ACTH 1-24 was studied in male rats. omega-Conotoxin (1-10 ng ICV 15 min before ACTH, 10 micrograms ICV), but not carboxymethylated omega-conotoxin, induced a dose-dependent prevention of all ACTH effects. In contrast, organic calcium channel inhibitors (20 mg/kg IP 30-60 min before ACTH) failed to modify ACTH-induced stretching and yawning but induced a 25% decrease in the number of penile erection episodes induced by the peptide, and prevented, like ICV omega-conotoxin, oxytocin- and apomorphine-induced yawning and penile erection. When injected in the paraventricular nucleus of the hypothalamus, omega-conotoxin prevented the above behavioral responses induced by apomorphine and oxytocin but not by ACTH 1-24. The present results suggest that ACTH induces stretching, yawning and penile erection by mobilizing calcium through central omega-conotoxin-sensitive calcium channels in brain sites different from those sensitive to oxytocin and apomorphine.

Animals↗
PubMed1993

Longitudinal study of plasma ACTH and cortisol in very low birth weight infants in the first 8 weeks of life.

There are few published data on plasma ACTH and cortisol in very low birth weight (VLBW) infants beyond the first week of life. We therefore measured plasma ACTH and cortisol longitudinally in 25 infants (mean birth weight 1025 g, mean gestational age 28 weeks) at 1, 2, 4 and 8 postnatal weeks to document normative values for infants not receiving dexamethasone. We also examined the influence of clinical state and dexamethasone treatment on plasma ACTH and cortisol levels. Median plasma ACTH increased significantly with advancing postnatal age from 1 week to 8 weeks (21.0 vs. 40.0 ng/l; P = 0.01) but did not correlate with postconceptional age. Median plasma cortisol decreased significantly with advancing postnatal age from 1 week to 8 weeks (216 vs. 50 nmol/l; P = 0.001) and correlated inversely with postconceptional age (P = 0.004). At 8 weeks infants who were clinically well (n = 6) had lower plasma ACTH values compared with sick (n = 6) infants (median: 37.0 vs. 63.5 ng/l; P = 0.033). Plasma ACTH did not correlate with clinical state at 1, 2 and 4 weeks. At none of the postnatal ages studied was plasma cortisol influenced by the degree of sickness. Five infants received dexamethasone to assist weaning from mechanical ventilation. Their median plasma ACTH level, at 8 weeks, was significantly lower than that of the 12 infants who did not receive dexamethasone (11.0 vs. 40.0 ng/l; P = 0.0006). Plasma cortisol was not significantly influenced by dexamethasone treatment (P = 0.27). These data provide further information on the evolution of adrenocortical function in VLBW infants in the first months of life.

Adrenocorticotropic Hormone↗
PubMed1996

Mifepristone modulation of ACTH and CRH regulation of bovine adrenocorticosteroidogenesis in vitro.

Mifepristone (RU486), bovine corticotropin-releasing hormone (CRH), arginine vasopressin (VP), adrenocorticotropin (ACTH1-24), and protein kinase activators (forskolin, [FSK]; phorbol 12-myristate 13-acetate [PMA]) were used in vitro to investigate their direct effect on adrenocorticosteroidogenesis. Bovine adrenocortical fasciculata/reticularis cells (2 x 10(5) viable cells/well) were cultured for 3 d in medium supplemented with 10% fetal calf serum. After incubation for an additional 24 hr in serum-free medium, cells were treated with serum-free medium alone (Control) or various concentrations of ACTH, CRH, VP, FSK, PMA, RU486, and/or various concentrations for 1, 2, 4, or 24 hr. Medium content of cortisol and progesterone were determined by radioimmunoassays. ACTH, CRH, FSK, and PMA each stimulated (P < 0.05) secretion of cortisol in time- and dose-related manners. Although these agents stimulated (P < 0.05) secretion of progesterone in a dose-related manner, medium content of progesterone declined (P < 0.05) over time. The minimal effective doses of ACTH and CRH required to stimulate (P < 0.05) secretion of cortisol relative to the Control over a 4-hr culture period were 0.01 nM and 3 nM, respectively. Relative to observations at 1 hr posttreatment, 24-hr treatment with ACTH or CRH increased the medium content of cortisol by an additional 19.8- and 48-fold, respectively (whereas content of progesterone declined over that time period). VP-stimulated secretion of cortisol was time- (P < 0.05) but not dose-related. Specifically, by 24-hr posttreatment, the medium content of cortisol was increased (P < 0.05) 4.6-fold relative to the quantity of cortisol secreted by 1-hr postaddition of VP (0.01 to 1 microM). Co-treatment with RU486 (1 microM) decreased (p < 0.05) FSK-, ACTH- and CRH-stimulated secretion of cortisol by 77, 27, and 56%, respectively. Similarly, the stimulatory effects of ACTH and CRH on progesterone secretion were reduced (P < 0.05) by 40 and 22%, respectively, by co-addition of RU486. The inhibitory action of RU486 on production of cortisol was no longer apparent by 24 hr after treatment. These observations indicate that RU486 can act as a steroid agonist and as well as an antagonist. These data characterize time- and dose-related direct actions of ACTH, CRH, and RU486 on adrenocorticosteroidogenesis. This information will assist efforts to clarify complex intra-adrenal interactions of neurohormones, growth factors, and endogenous steroids.

Adrenal Cortex↗
PubMed1994

Cloning of ACTH-regulated genes in the adrenal cortex.

To search for genes that are induced by ACTH in adrenocortical cells, we screened adrenal cortex cDNA libraries by a differential hybridization method using cDNA probes representing mRNAs from cells with or without ACTH stimulation. Forty clones were identified as ACTH induced (yielding a frequency of about 1/2500 plaques screened), and two clones as ACTH repressed. The cDNAs isolated and sequenced include nuclear genes for microsomal steroidogenic enzymes and novel proteins of yet unidentified functions, and mitochondrial genes encoding subunits of oxidative phosphorylation enzymes. Northern blot analysis of RNA from cells stimulated with ACTH confirmed the induction of these genes by ACTH, yet revealed important differences in the relative responses of the respective mRNAs. The time courses showed the major increase in the initial 6 h; and a decline after 24-36 h. The enhancement of the levels of the mRNAs could be ascribed to transcriptional activation. Since the mitochondrial genome is transcribed as a single polycistronic unit, to account for the > 20-fold differences in the levels of the mitochondrial mRNAs it is necessary to invoke differential stabilities of these mRNAs. The synchronous increase in the expression of both the steroidogenic enzymes and the mitochondrial oxidative phosphorylation system subunits, provides evidence for coregulation of steroidogenic and energy producing capacities of adrenal cells to meet the metabolic needs of steroid hormone production. Suppression of beta-actin gene expression may be related to changes in actin polymerization during ACTH-dependent cytoskeletal reorganization.

Adrenal Cortex↗
PubMed2004

ACTH-producing cells of 21-day-old rat fetuses after maternal dexamethasone exposure.

Adrenocorticotrophic hormone (ACTH) is essential for developmental maturation of numerous organ systems during the fetal period and for adaptation to environmental challenges. Immunocytochemical and stereological methods were used in the present study to examine the effects of dexamethasone (Dx) administration during pregnancy on fetal rat pituitary ACTH-producing cells. Doses of 0.5, 0.5 and 1.0 mg Dx/kg body weight/day were given to the dams on 3 consecutive days starting on day 16 of gestation. Morphometric analysis of the ACTH-producing cells of fetuses at 21 days of gestation revealed significant inhibition by 24% and 27%, respectively, of cell volume and cell number after maternal Dx administration, whereas the volume of cell nuclei and volume density of ACTH-stained cells were insignificantly decreased. Immunocytochemical analysis showed reduced numbers, sizes and immunopositivity of ACTH cells of 21-day-old fetuses from Dx-treated dams as compared with the control group. Maternal Dx treatment in the period of intense differentiation of the hypothalamo-hypophyseal-adrenal system had an inhibitory effect on fetal function and proliferative activity of ACTH-producing cells at 21 days of gestation. Thus, inhibition of activity of fetal ACTH-producing cells may lead to adrenal suppression, modified activity of the hypothalamo-pituitary-adrenal axis and reduced body weight possibly causing lasting functional abnormalities.

Adrenocorticotropic Hormone↗
PubMed2006

Effect of ACTH (tetracosactide) on steroid hormone levels in the mare. Part A: effect in intact normal mares and mares with possible estrous related behavioral abnormalities.

Ovariectomized mares and mares with inactive ovaries may show signs of estrus. The reason behind this phenomenon is not clear; however, steroid hormones of adrenal origin have been suggested. Moreover, aberrant adrenal hormone production has been implied as a reason why some intact mares may change behavior. In the present study, the effect of ACTH on plasma levels of cortisol, progesterone, androstenedione and testosterone was investigated in intact mares with normal estrous behavior ('controls', n=5) and intact mares that according to their owners showed deviant estrous behavior ('problem' mares, n=7). Blood samples were collected hourly from 12:00 h until 14:00 h the following day (half-hourly between 14:00 and 17:00 h) on two occasions (at two estruses), with saline or ACTH treatment (tetracosactide) at 14:00 h (saline treatment day or ACTH treatment day). ACTH treatment caused a significant increase in plasma levels of cortisol, progesterone, androstenedione and testosterone in all mares (P<0.05). An overall significant difference in cortisol response to ACTH was found (P<0.05), with 'problem' mares showing a significantly lower increase in cortisol levels 30 min to 3h post ACTH treatment (P<0.001). The 'problem' mares also showed a significantly higher increase than controls in progesterone levels in the same time period (P<0.05). The reason for the reduced adreno-cortical reactivity, with a low cortisol response to the ACTH treatment, in the 'problem' mares is unknown, but may indicate a difference in adrenal function as compared to control mares.

Androstenedione↗
PubMed2005

Extremely low-dose ACTH step-up protocol for West syndrome: maximum therapeutic effect with minimal side effects.

We studied the effectiveness of our new ACTH treatment strategy for West syndrome (WS), which was based on the results of our previous extremely low-dose ACTH study. The subjects were 31 infants with WS (cryptogenic WS in nine; symptomatic WS in 22). Synthetic ACTH-Z in a dose of 0.005 mg (= 0.2 IU)/kg/day was injected once every morning for at least 2 weeks, up to a maximum of 3 weeks. When this first treatment course achieved full seizure and EEG control, ACTH was tapered to zero over the subsequent 1 or 2 weeks. In the absence of a documented response, the dosage was increased to 0.025 mg (= 1.0 IU)/kg/day for the next 2 weeks (second treatment course). We analyzed the short-term as well as long-term effects, and the incidence of side effects. The first treatment course successfully controlled both spasms and hypsarrhythmia in 17 patients (55%), only spasms in one, and hypsarrhythmia in two. The second treatment course was then introduced in eight of the remaining 14 patients, providing complete suppression of WS in an additional two patients. Regarding the long-term effects, 13 patients (48%), with excellent short-term results and a longer than 1-year follow-up, remained seizure-free. Side effects of a mild degree were seen in 13 patients during ACTH treatment. Our new ACTH step-up method brought 61 and 48% of the patients into short-term and long-term remission, respectively, without significant side effects. The dose of ACTH required to control WS appears to be unexpectedly smaller than the dose we previously used.

Adrenocorticotropic Hormone↗
PubMed2006

Sex differences in the ACTH response to 24H metyrapone in depression.

Increased hypothalamic-pituitary-adrenal (HPA) axis activation has been observed in major depression. Increased corticotropin-releasing hormone (CRH) is hypothesized to drive corticotropin (ACTH) secretion leading to increased ACTH and cortisol secretion throughout 24H. Contradicting data exist as to whether the increased drive is present throughout the day or is restricted to the late afternoon and evening. To determine if increased HPA axis activation occurs during a specific circadian phase or is found throughout the 24H, we studied 26 healthy drug-free depressed patients and 26 healthy age- and sex-matched control subjects under metyrapone inhibition of cortisol synthesis for 24H beginning at 4 PM. Blood was drawn every 10 min for 24H and assayed for ACTH and cortisol. Gender differences in response to metyrapone were seen in both patients and controls. Depressed women demonstrated increased ACTH concentrations between 4 PM and 10 PM compared to control women. Maximal ACTH response over time was identical between depressed and control women. Depressed men demonstrated significantly decreased ACTH secretion between 4 and 10 PM as well as decreased maximal ACTH response compared to control men or depressed women. These data support an increased evening CRH drive in depressed women, but overall decreased CRH drive in depressed men.

Adrenal Cortex↗
PubMed2004

Molecular mimicry of ACTH in SARS - implications for corticosteroid treatment and prophylaxis.

For a virus to survive and replicate in an organism, it must employ strategies to evade and misdirect the host's immune response. There is compelling evidence that the primary immunoevasive strategy utilized by the SARS virus, like influenza, is to inhibit its host's corticosteroid stress response. This is accomplished by viral expression of amino acid sequences that are molecular mimics of the host's adrenocorticotropin hormone (ACTH). When the host produces antibodies against these viral antigens, the antibodies also bind to the host's own ACTH, which limits the host's stress response by interfering with ACTH's ability to stimulate the secretion of corticosteroids. This inadequate corticosteroid response provokes symptoms as a result of a relative adrenocortical insufficiency. Treatment with corticosteroids can relieve the patient's symptoms of adrenocortical insufficiency and give them the corticosteroid levels needed to fight their infection. Similarly, by taking moderate daily doses of corticosteroids as a prophylactic, it may be possible to avoid clinical infection with SARS. If SARS's ACTH mimic strategy never has an opportunity to get started, SARS's ability to evade its host's immune system while its viral load is low will be significantly impaired. In this article, amino acid sequences from the SARS and influenza viruses representing likely homology to human ACTH are identified. Evidence demonstrating that ACTH autoantibodies are produced during influenza infection is also presented. Early treatment with corticosteroids should lower the dose necessary to counteract SARS's ACTH autoantibody mechanism. If corticosteroid treatment is delayed until inflammatory cytokine levels are causing serious injury, only high doses of corticosteroids are likely to be effective.

Adrenal Cortex Hormones↗
PubMed2005

Male patients with paranoid schizophrenia have greater ACTH and cortisol secretion in response to metoclopramide-induced AVP release.

Dynamic testing of the hypothalamic-pituitary-adrenal axis in schizophrenia has yielded conflicting results, which may be related to patient selection and previous exposure to psychotropic medication. The objective of this study was to determine the pattern of corticotropin (ACTH) and cortisol release in response to metoclopramide (a dopamine antagonist), which appears to be unique in its ability to release vasopressin (AVP), in drug naive patients with schizophrenia experiencing their first episode of psychosis. In this study, we examined AVP, ACTH and cortisol release in response to metoclopramide in 10 drug-naive, first-episode male patients with a DSM IV diagnosis of paranoid schizophrenia and compared them to healthy control subjects matched for age, sex and smoking status. Patients, as compared to controls had higher levels of baseline plasma cortisol (375.5+/-47.4/l vs. 273.8+/-42.2 nmol/l, respectively; t=2.48, df=9, p< 0.02) and plasma ACTH (14.9+/-0.85 vs. 11.3+/-0.57 pg/ml, respectively; t=4.29, df=9, p<0.001). AVP levels were lower in patients though this did not reach statistical significance (0.89+/-0.09 vs. 1.3+/-0.08 pmol/l, respectively; t=1.97, df=9, p<0.07). A repeated measures 2-way ANOVA to compare responses to metoclopramide over time between the two groups yielded a significant group by time interaction for cortisol (F=11.3, df=6, 108, p<0.001) and ACTH (F=15.65, df=6, 108, p<0.002). Post hoc Tukey's test revealed significant differences between the two groups at +30, +45, +60, +90 and +120 min for cortisol (p<0.01) and at +30, +45, +60 and +90 min for ACTH (p<0.01). The group by time interactions continued to remain significant when cortisol (F=10.9, df=6, 107, p<0.001) and ACTH (F=13.04, df=6, 108, p<0.002) were entered as co-variates. There was a significant positive correlation between AVP and cortisol responses in patients (r=0.65, df=8, p<0.01). Male patients with paranoid schizophrenia release greater amounts of ACTH and cortisol in responses to metoclopramide-induced AVP secretion than control subjects.

Adrenocorticotropic Hormone↗
PubMed2005

Use of ACTH and prednisolone in infantile spasms: experience from a developing country.

BACKGROUND: Adrenocorticotrophic hormone (ACTH) and prednisone are both used to treat infantile spasms (IS) in West syndrome. In many countries, ACTH is expensive and difficult to obtain whereas, prednisone or prednisolone are cheap, given orally and easily available. AIMS: The purpose of this retrospective data analysis was to compare the efficacy and cost of ACTH and prednisolone in the treatment of IS from the perspective of a developing country. METHODS: Patients admitted with West syndrome in Children's Hospital, Islamabad, between January 1995 and December 2001 were included in the analysis. The diagnosis was made after eliciting a history of characteristic seizures and detecting hypsarrhythmia on the EEG. Parents were offered the use of either ACTH administered by intramuscular injection or prednisolone given orally. ACTH was expensive and difficult to obtain whereas prednisolone was cheap and easily available. RESULTS: One hundred and five children were included in the study. Sixty-three were boys and their age ranged from 2 months to 3 years with a mean of 11 months. Thirty-three children received ACTH injections; 27 showed improvement and 11 remained spasms free after discontinuation of injections. Seventy-two patients were given oral prednisolone, 51 responded and 17 remained spasms free after oral steroids were stopped. Overall outcome was similar in both groups. The cost of ACTH injection was more than 100 times the cost of oral prednisolone. CONCLUSION: No significant difference was seen in the final outcome in both treatment groups. Since prednisolone is inexpensive, easily available and given orally, it is the preferred mode of therapy.

Adrenocorticotropic Hormone↗