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PubMed1997

Arginine-vasopressin stimulates CRH and ACTH release by rat adrenal medulla, acting via the V1 receptor subtype and a protein kinase C-dependent pathway.

Arginine-vasopressin (AVP) is a hypothalamic hormone that, like CRH, stimulates the pituitary release of ACTH, thereby activating adrenal glucocorticoid secretion. Evidence indicates that rat adrenal medulla contains a CRH-ACTH system duplicating that existing at the hypothalamo-pituitary level and involved in the paracrine stimulation of the cortex secretion. Therefore, we investigated by RIA the effect of AVP on the release of CRH and ACTH immunoreactivities (IR) by rat adrenal medulla in vitro. AVP concentration-dependently enhanced the release of both CRH-IR and ACTH-IR, and the effect was blocked by a selective antagonist of the V1 subtype of AVP receptors. The CRH receptor antagonist alpha-helical-CRH partially reversed AVP-evoked rise in ACTH-IR release, without altering either CRH response or basal secretions of CRH and ACTH. The specific inhibitors of protein kinase C Ro31-8220 and calphostin C abolished both CRH and ACTH responses to AVP. In conclusion, our present findings suggest that AVP stimulates intramedullary the CRH-ACTH system, acting via V1 receptors and activating protein kinase C.

Adrenal Medulla↗
PubMed1985

ACTH and related peptides: molecular biology, biochemistry and regulation of secretion.

The precursor of ACTH and beta-LPH is a glycoprotein with a molecular weight of more than 30 000. Its gene consists of three exons with two intervening sequences and most of the protein coding sequence is in exon 3. The gene is expressed not only in the pituitary gland but also in extrapituitary tissues. The gene expression in the anterior pituitary gland is regulated by CRF and glucocorticoids, but it is regulated differently in other tissues. The processing of the ACTH/beta-LPH precursor yields several peptides, but final products vary in tissues due to differential processing. The processing is abnormal in ACTH-producing tumours, especially in ectopic ACTH-producing tumours. Some abnormalities may also occur at the transcriptional or post-transcriptional level as well. Peptides derived from the same precursor are secreted concomitantly from the pituitary gland. CRF is the major stimulating factor, but vasopressin and some other factors are also involved in stimulating ACTH release. On the other hand, glucocorticoids inhibit ACTH release by acting at the hypothalamic and pituitary levels. In the pituitary ACTH-producing adenomas of Cushing's disease, CRF, vasopressin as well as other non-physiological factors stimulate ACTH secretion. Such abnormal receptor mechanisms are also seen in ectopic ACTH-producing tumours.

Adrenocorticotropic Hormone↗
PubMed2001

Over-expression of NCS-1 in AtT-20 cells affects ACTH secretion and storage.

The effect of over-expressing neuronal calcium sensor 1 (NCS-1) upon stimulated adrenocorticotrophin (ACTH) secretion was studied in AtT-20 cells. Stably-transfected AtT-20 cell lines over-expressing NCS-1 were obtained and compared to wild type AtT-20 cells. Corticotrophin releasing factor (CRF-41)-stimulated ACTH secretion from NCS-1 over-expressing cells was significantly reduced from that obtained in wild type AtT-20 cells. The effects of other stimulants of ACTH secretion from wild type AtT-20 cells were not attenuated in NCS-1 over-expressing cells. Calcium, guanosine 5'-O-(3'-thiotriphosphate) (GTP-gamma-S) and mastoparan stimulated ACTH secretion from permeabilised wild type AtT-20 and NCS-1 over-expressing AtT-20 cells with significantly greater ACTH secretion obtained in NCS-1 over-expressing cells. This study shows that in intact cells over-expression of NCS-1 reduces exocytotic ACTH release, while in permeabilised cells increases ACTH release. NCS-1 has multiple cellular targets and that directly and indirectly via these targets acts to increase the releasable ACTH pool while inhibiting CRF-41 stimulus-secretion coupling.

Adrenocorticotropic Hormone↗
PubMed1998

Effects of ACTH administration on zonation of the guinea pig adrenal cortex.

Experiments were done to determine the actions of ACTH on the morphologic and functional characteristics of the zona fasciculata (ZF) and zona reticularis (ZR) in the guinea pig adrenal cortex. In control guinea pigs, a number of morphologic differences distinguished the ZF from the ZR, including the presence of far more lipid in the ZF than in the ZR. Treatment with ACTH decreased the lipid droplet content of the ZF cells, equalizing the amount of lipid in the two zones. Other morphologic differences between the ZF and ZR were also diminished by ACTH treatment. Immunohistochemical analyses indicated that CYP17 protein was found in both the ZF and ZR in control animals, but with greater immunostaining intensity in the ZF. The enzyme protein distribution corresponded with higher 17alpha-hydroxylase activity in the ZF than in the ZR. After ACTH treatment, the intensity of staining and enzyme activities in the two zones were similar, attributable largely to increases in the ZR. In situ hybridization-and immunohistochemistry showed that in control animals CYPD216 was highly expressed in the ZR but not in the ZF. ACTH treatment dramatically reduced the intensity of CYP2D16 mRNA and protein staining in the ZR. Bufuralol 1'-hydroxylase activity, a marker for CYP2D subfamily members, was also decreased significantly in the ZR by ACTH treatment. The data indicate that administration of ACTH to guinea pigs has opposite effects on the expression of CYP17 and CYP2D16 in the ZR, and diminishes or eliminates some of the structural and functional differences between the ZF and ZR. The results suggest a role for ACTH in establishing and maintaining adrenocortical zonation.

Adrenal Cortex↗
PubMed2001

ACTH therapy of West syndrome: Finnish views.

To provide up-to-date information on adrenocorticotropic hormone (ACTH) therapy in the treatment of West syndrome, a review of the Finnish studies was made in answer to the questions: what are (1) its efficacy: doses and comparison with vigabatrin (VGB), (2) its tolerability, (3) its mechanism of action? Why do some patients respond, but others do not? No other drugs have been shown to be more effective than ACTH. High doses were not more effective than low doses. Synthetic derivatives were associated with more frequent side effects. Individualized therapy was developed on the basis of etiology and response. With therapy consisting of ACTH 3-6IU/kg/day, all the cryptogenic and half of the symptomatic spasms could be controlled within over 2-3 weeks therapy and with minimal risk of side effects. In a Finnish study, 26% of the patients responded to VGB as the first-line drug. Some of the non-responders responded to ACTH. In tuberous sclerosis, the initial response rate to ACTH was high (73%) and did not differ from the response rate to VGB in other series. Both drugs have severe side effects. The visual field defects caused by VGB occur even in children (in 18/91 Finnish children). The patients with cryptogenic spasms, who responded well to ACTH, differed in their biochemical parameters from the patients with symptomatic spasms. The therapeutic action of ACTH may be mediated by potentiation of nerve growth promoting activity. Neurodegeneration may be due to imbalance between nerve growth factors and nitrate/nitrite in the brain. ACTH should be used as the first choice for treatment of West syndrome (at the minimal effective dose and for shortest effective time). The side effects of steroids, unlike VGB, are well known, treatable, and reversible.

Adrenocorticotropic Hormone↗
PubMed1989

Chronic ACTH treatment increases striatal dopamine D-2 receptor binding in developing rat brain.

ACTH has been reported to decrease elevated levels of dopamine metabolites in the CSF of patients with infantile spasms who respond clinically to ACTH therapy. To study the possible role of dopamine receptors in the effect of ACTH, we treated rat pups for thirty days with 40 IU/kg subcutaneously of porcine ACTH or with normal saline. Using 10 nM 3H-spiperone and sulpiride to determine nonspecific binding, specific binding of D-2 receptors increased significantly (46%) in the striata of ACTH-treated rats when compared to controls. No significant difference in specific binding was found in the nucleus accumbens. Protein concentration was significantly decreased by ACTH treatment. Saturation studies will be necessary to determine if the increase in dopamine receptor binding induced by a high dose of ACTH represents a change in receptor density or affinity. The effect of lower clinical doses of ACTH on dopamine receptors warrants study.

Adrenocorticotropic Hormone↗
PubMed2001

Twenty-four-hour ACTH and cortisol pulsatility in depressed women.

Increased plasma cortisol in patients with major depression is a well documented finding, although it is present in only 25-30% of subjects with major depression. However, ACTH and cortisol are secreted in a pulsatile manner, so it is unclear if increased ACTH secretion occurs in depression and if there are changes in the pulsatile components of ACTH secretion. Ten-minute sampling for ACTH and cortisol was performed for 24 hr in 25 premenopausal depressed women, whose age and menstrual cycle day matched control women. As a group, the depressed women demonstrated a trend to increase cortisol secretion (p = 0.089). There was no difference in mean cortisol between the patient group as a whole (8.36 +/- 2.9 microg/dl) and those patients meeting criteria for atypical depression (8.38 +/- 1.9 microg/dl), but patients meeting criteria for endogenous showed increased cortisol (12.17 +/- 4 microg/dl) Mean ACTH was not significantly different between patients and controls. Pulse analyses revealed similar number of secretory events and similar amplitudes for cortisol secretory bursts in patients and controls. The baseline component area under the curve of cortisol secretion was increased at a trend level (p =.064) in depressed patients, and the baseline AUC for ACTH was significantly increased in depressed patients (p =.045). No differences were found in pulsatile components of ACTH secretion between patients and matched controls. Harmonic analyses indicated no significant differences between patients and controls on any detected rhythm for ACTH or cortisol. These data suggest that the pulsatile and circadian components of the HPA axis are normal in premenopausal depressed women and that only 24% of depressed women demonstrate hypercortisolemia.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Cyclic AMP-independent effects of ACTH on glomerulosa cells of the rat adrenal cortex.

The aim of the present paper is to point out the complexity of ACTH action in glomerulosa cells of the adrenal cortex. We demonstrate that the increase in cAMP production induced by ACTH is the result of a balance between activation of adenylyl cyclase and direct modulation of a PDE2 phosphodiestease activity, an effect mediated by inhibition of cGMP content. Moreover, Ca2+ is essential for cAMP production and aldosterone secretion, but its exact primary action is not clearly determined. We recently described that ACTH activated a chloride channel, via the Ras protein, which can be involved in steroidogenesis. ACTH also increases tyrosine phosphorylation of several proteins. These data, together with those of phospholipase C activation, indicate that ACTH action in the adrenal is complex, and most certainly not limited to cAMP production, in particular for the low concentrations of the hormone. Some years ago, cAMP was considered to be the unique second messenger of ACTH action; now it becomes more and more evident that ACTH triggers complex signaling pathways using several second messengers in a closely interacting way. The most predominant point is that these signals are observed for low concentrations of ACTH.

Adrenocorticotropic Hormone↗
PubMed1998

Modulation of adrenal cell functions by cadmium salts. 5. Cadmium acetate and sulfate effects on basal and ACTH-stimulated steroidogenesis.

In vitro and in vivo cadmium toxicity studies focus almost exclusively on CdCl2 effects. Only a few studies have used adrenocortical cells and tissue to determine cadmium salt effects during stress of adrenocorticotropin stimulation. Because several biologically relevant water-soluble cadmium salts exist, this study extended work with CdCl2 to evaluate the acute adrenocortical cell steroid secretory responses to non-lethal cadmium acetate (CdAc2) and CdSO4 concentrations. Control or ACTH-stimulated cultured Y-1 mouse adrenal tumor cells (ATCC) which secrete 20alpha-dihydroprogesterone (20-DHP) were incubated for 0.5 h in serum-free medium (FMEM) with or without 0.5, 1.0, 5.0, 10.0, 50.0, 100.0, 500.0 and 1000.0 microg CdAc2 or CdSO4/ml FMEM (1.9, 3.8, 19.0, 38.0, 190.0, 380.0 and 1900.0 micromol/L, respectively). For each salt, cell viability was measured at the end of the incubation using live cell trypan blue exclusion. In addition, cumulative CdAc2 effects during 4 h incubations and effect reversibility were determined for control and stimulated cells. After each experimental incubation, the 20-DHP secreted into the medium was determined by radioimmunoassay. Over 80% of all control or ACTH-stimulated cells were viable after incubation in the presence or absence of various CdAc2 or CdSO4 concentrations. Cadmium acetate and sulfate inhibited basal and ACTH-stimulated steroid secretion in a dose-dependent manner. For basal steroid secretion the CdAc2 concentration that first significantly inhibited was 0.5 microg/ml medium (1.9 micromol/L); stimulated secretion was significantly inhibited beginning at 5.0 microg/ml (19.0 micromol/L) and the concentration reducing stimulated 20-DHP secretion by 50% (IC50) was 5.6 microg/ml (21.3 micromol/L). Similarly, the first CdSO4 concentration to significantly inhibit basal and ACTH-stimulated steroid secretion was 10.0 microg/ml medium (39.0 micromol/L); the IC50 was 7.8 microg/ml (29.8 micromol/L). Except that basally secreting Cd2+-treated cells almost doubled 20-DHP secretion after Cd2+ removal and subsequent incubation with ACTH, all basal and ACTH-stimulated steroid secretion was irreversibly inhibited by every CdAc2 concentration. All CdAc2 concentrations initiated and maintained cumulative inhibitory effects on basal and ACTH-stimulated steroid secretion over a 4 h period. Reversibility and cumulative CdSO4 treatment studies were not conducted. Based on the results from the present studies, both CdAc2 and CdSO4 appeared to incrementally inhibit control and ACTH-stimulated steroidogenesis without affecting cell viability and to be more potent inhibitors of adrenocortical cell steroid secretion than CdCl2. Finally, CdAc2 effects on control and stimulated cells were cumulative and irreversible.

20-alpha-Dihydroprogesterone↗
PubMed1985

Administration of dexamethasone prior to training blocks ACTH-induced recovery of an extinguished avoidance response.

Pretest administration of ACTH has been shown to produce recovery of an extinguished avoidance response. Presumably this effect is found because endogenous ACTH is a component of the original training memory. However, another possible explanation of this finding is that administration of the peptide acts as a novel stimulus that "disinhibits" the extinguished response. In order to test this "disinhibitory" hypothesis of ACTH-induced recovery of an extinguished avoidance response, some subjects were given dexamethasone 2 hr prior to training and extinction. This synthetic glucocorticoid is effective in blocking endogenous release of ACTH. Thus, ACTH should not be a component of the training memory in subjects given dexamethasone prior to training and extinction but would be a relatively novel stimulus condition at testing. Pretest administration of ACTH was found to be effective in alleviating performance deficits induced by extinction only for subjects given saline prior to training and extinction. Administration of ACTH had no effect on the avoidance responding of subjects given dexamethasone. These findings suggest that pretest administration of ACTH affects retrieval processes rather than acts as a disinhibitor.

Adrenocorticotropic Hormone↗
PubMed1978

ACTH and ACTH4-10 modification of neophobia and taste aversion responses in the rat.

A series of experiments assessed the effects of ACTH and the ACTH analogue ACTH4-10 on drinking in conditioned taste aversion and neophobic situations. Both substances delayed the extinction of a conditioned taste aversion established by a single pairing of lithium chloride with milk (Experiment 1). However, in this situation, the ACTH parent peptide was more potent behaviorally. Administration of ACTH suppressed milk consumption in animals with no toxicosis experience (Experiment 2). This effect was apparently not due to the conditioning of a taste aversion (Experiment 3) with ACTH serving as a weak aversive unconditioned stimulus. Administration of exogenous ACTH (Experiment 4) or ACTH4-10 (Experiment 5) did not enhance neophobia; however, repeated injections of ACTH suppressed drinking. This ACTH suppression was related to the familiarity/novelty of the subtance being consumed. The neophobic response to milk eas no accompanied by pituitary-adrenal activation (Experiment 6). Both neophobic and conditioned taste aversion situation appear to be useful for assessing peptide effects on consummatory behavior.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

The vasopressin receptor antagonist dPTyr (Me) AVP does not prevent stress-induced ACTH and corticosterone release.

Most of the experimental evidence for a role of arginine-vasopressin (AVP) in adrenocorticotropic hormone (ACTH) release comes from in vitro studies. The multimolecular nature of the hypothalamic factor responsible for corticotropin (CRF) release has long been recognized, but the importance of AVP as a cofactor is controversial. The recently characterized 41-residue peptide fulfills the criteria for a physiological role in ACTH release and it is potentiated in vitro by AVP. In vivo, AVP is able to stimulate ACTH secretion, and Brattleboro rats, deficient in AVP, show a reduced activity of the hypothalamo-hypophysial-adrenocortical system (HHCS) (see ref. 13 for references). Direct evidence for involvement of AVP in the physiological release of ACTH is, however, still lacking. The recent development of AVP receptor antagonists provides the opportunity to test this hypothesis directly. I report here that pretreatment by 1-deaminopenicillamine, 2-(O-methyl)tyrosine arginine-vasopressin (dPTyr(Me)AVP), a potent antagonist of the vasopressor, behavioural and ACTH-releasing properties of AVP, does not modify the ACTH and corticosterone secretion induced by exposure to a novel environment, but totally inhibits the increase of ACTH and corticosterone levels induced by AVP. The results do not support the hypothesis for a physiological involvement of AVP in ACTH release.

Adrenocorticotropic Hormone↗
PubMed1997

Different cardiovascular profiles of three melanocortins in conscious rats; evidence for antagonism between gamma 2-MSH and ACTH-(1-24).

1. We investigated the effects of [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH), adrenocorticotropin-(1-24) (ACTH-(1-24)) and gamma 2-MSH, three melanocortins with different agonist selectivity for the five cloned melanocortin receptors, on blood pressure and heart rate in conscious, freely moving rats following intravenous administration. 2. As was previously found by other investigators as well as by us gamma 2-MSH, a peptide suggested to be an agonist with selectivity for the melanocortin MC3 receptor, caused a dose-dependent, short lasting pressor response in combination with a tachycardia. Despite the fact that NDP-MSH is a potent agonist of various melanocortin receptor subtypes, among which the melanocortin MC1 receptor, it did not affect blood pressure or heart rate, when administered i.v. in doses of up to 1000 nmol kg-1. 3. ACTH-(1-24) caused a dose-dependent decrease in blood pressure in combination with a dose-dependent increase in heart rate in a dose-range from 15 to 500 nmol kg-1. The cardiovascular effects of ACTH-(1-24) were independent of the presence of the adrenals. 4. Pretreatment with ACTH-(1-24) caused a pronounced, dose-dependent parallel shift to the right of the dose-response curve for the pressor and tachycardiac effects of gamma 2-MSH. The antagonistic effect of ACTH-(1-24) was already apparent following a dose of this peptide as low as 10 nmol kg-1, which when given alone had no intrinsic hypotensive activity. 5. These results form further support for the notion that it is not via activation of one of the as yet cloned melanocortin receptors that gamma-MSH-like peptides increase blood pressure and heart rate. The cardiovascular effects of ACTH-(1-24) seem not to be mediated by the adrenal melanocortin MC3 receptors, for which ACTH-(1-24) is a selective agonist, or by adrenal catecholamines. 6. There appears to be a functional antagonism between ACTH-(1-24) and gamma 2-MSH, two melanocortins derived from a common precursor, with respect to their effect on blood pressure and heart rate. Whether this antagonism plays a (patho)physiological role remains to be shown.

Adrenal Medulla↗
PubMed1996

Failure of the short ACTH test to unequivocally diagnose long-standing symptomatic secondary hypoadrenalism.

Recent guidelines propose that secondary hypoadrenalism can be reliably diagnosed, in the absence of acute ACTH deficiency or glucocorticoid use, by means of the short ACTH test (Synacthen). We report a patient who maintained a normal response to exogenous ACTH stimulation despite symptomatic chronic ACTH deficiency proven by the insulin tolerance and overnight metyrapone tests. It is suggested that partial ACTH deficiency may prevent involution of the adrenal cortex and preserve the cortisol response to ACTH stimulation. A normal cortisol response in the short ACTH test does not therefore exclude the possibility of clinically relevant ACTH deficiency.

Adrenal Cortex Function Tests↗
PubMed1999

ACTH and cortisol release following intravenous desmopressin: a dose-response study.

OBJECTIVE: Desmopressin (DDAVP) is a synthetic analogue of AVP, the companion regulator of corticotrophin-releasing hormone (CRH) in the control of ACTH synthesis and release from the pituitary corticotrophs. The body of evidence from human studies suggests that DDAVP alone, unlike AVP, does not bring about ACTH release, although recent evidence suggests idiosyncracies of response in healthy subjects. We examined whether DDAVP exerted any consistent effect on ACTH and cortisol release, and also if this occurred in a dose-dependant manner. DESIGN AND SUBJECTS: A total of 18 subjects participated in the study. Saline, 5 microg, 10 microg and 15 microg DDAVP were administered as an intravenous bolus at 1300 h; 5, 7, 18 and 8 subjects, respectively, participated in each arm of the study. Plasma ACTH and cortisol responses were measured over a 120-minutes period. RESULTS: Significant between group comparisons were demonstrated for both ACTH (P < 0.05) and cortisol responses (P < 0. 005) measured as maximum increment from baseline. The ACTH response to 5, 10 and 15 microg DDAVP was significantly greater than saline at all three doses, whilst maximal responses were seen at 10 microg. The cortisol responses to 10 and 15 microg DDAVP doses, but not 5 microg, were significantly greater than following saline. 11/18 subjects were deemed 'responders' following 10microg DDAVP on the basis of both ACTH and cortisol output. CONCLUSIONS: This data suggests that DDAVP is capable of stimulating ACTH and cortisol release when administered alone as a bolus in over 50% of healthy subjects. This is in contrast to much of the extant literature. The mode of administration may be pertinent to this effect. This finding has implications for the recent focus on DDAVP as a diagnostic tool in disorders such as Cushing's Disease.

Adrenocorticotropic Hormone↗
PubMed2000

Low-dose (1 microgram) adrenocorticotrophin (ACTH) stimulation as a screening test for impaired hypothalamo-pituitary-adrenal axis function: sensitivity, specificity and accuracy in comparison with the high-dose (250 microgram) test.

OBJECTIVE: We have shown previously that in contrast to the standard high-dose 250-microgram ACTH test, a low-dose 1-microgram ACTH stimulation test correctly identified all patients with pituitary disease who had impaired hypothalamo-pituitary-adrenal (HPA) function. In this study we further compared the performances of these two tests as screening procedures for possible HPA impairment. DESIGN: A comparison of the 1-microgram and the 250-microgram ACTH stimulation tests in healthy controls and in patients with pituitary disease whose HPA axis status was characterized formally by a gold standard test. SUBJECTS: A total of 89 subjects were investigated: 27 healthy normal controls, 43 patients with pituitary disease and normal HPA function, and 19 patients with various pituitary diseases and impaired HPA function. MEASURES: All 89 subjects underwent stimulation with 1 microgram ACTH; 80 also underwent the high-dose 250-microgram ACTH test. A receiver operating characteristic analysis (ROC) was performed to compare the tests. RESULTS: Using a stimulated cortisol > 500 nmol/l as the criterion for a normal response, the 1-microgram ACTH stimulation identified 18 of the 19 subjects with impaired HPA function (94.7% sensitivity with a likelihood ratio of 0.0588 for a negative test). In contrast, 15/16 passed the high-dose test (a 6.2% sensitivity with a likelihood ratio of 0.875 for a negative test). All normal controls, and 36/43 patients with preserved HPA function, passed the 1-microgram ACTH test (90% specificity). This degree of accuracy was unrivalled by the high dose test at all the cut-off levels considered. CONCLUSIONS: More sensitive and accurate, the low-dose 1-microgram ACTH test is as simple and safe as the standard 250-microgram test. We suggest it should replace it in screening for adrenal insufficiency.

Adrenal Insufficiency↗
PubMed1999

Beneficial effects of ACTH on the serum lipoprotein profile and glomerular function in patients with membranous nephropathy.

BACKGROUND: Previous studies have shown that short-term treatment with adrenocorticotrophic hormone (ACTH) has a strong and rapid lipid-lowering effect. In this long-term study of nephrotic patients with idiopathic membranous nephropathy, the influence of ACTH on the serum lipoprotein profile and glomerular function as well as the dose-effect relationship was investigated. METHODS: Fourteen patients received ACTH intramuscularly at increasing doses during 56 days. Serum concentrations of lipids, lipoproteins, and apolipoproteins as well as variables of glomerular function were analyzed, and the side-effects were recorded. ACTH treatment, in the estimated optimal dosage, was then continued in five patients with severe steroid-resistant nephrotic syndrome. In these five patients, the total treatment period was 12 months, and the follow-up time after discontinuing treatment was 18 months. RESULTS: Taking both the statistically significant therapeutic effects and the modest side-effects into consideration, the optimal dosage of ACTH was estimated to be 1 mg twice per week. At that dose, reductions by 30 to 60% in the serum concentrations of cholesterol, triglycerides, apolipoprotein B, and lipoprotein(a) were observed, whereas the serum concentrations of high-density lipoprotein cholesterol and apolipoprotein AI rose by 30 to 40%. In addition, the urinary albumin excretion decreased by 90%, and the glomerular filtration rate increased by 25%. Deterioration was observed in all cases when ACTH was discontinued after a treatment duration of 56 days. However, the five patients in whom ACTH therapy was resumed were still in remission 18 months after discontinuance of treatment. CONCLUSIONS: In nephrotic patients with idiopathic membranous nephropathy, treatment with ACTH 1 mg twice per week was associated with significant long-term improvements in serum lipoprotein pattern and glomerular function.

Adrenocorticotropic Hormone↗
PubMed1985

Effects of continuous alpha (1-24) ACTH infusion in the dog.

Dogs chronically infused with alpha (1-24) ACTH for 2 weeks showed continuous elevations in plasma ACTH, cortisol, and progesterone levels. Haematologic changes included immediate increases in numbers of mature neutrophils and monocytes and reduced numbers of eosinophils and lymphocytes. Haematocrits were also reduced with ACTH infusion. Whereas serum potassium levels fell in association with ACTH, serum sodium was unchanged. Activities of two serum enzymes of probable liver origin, alkaline phosphatase and alanine aminotransferase, increased gradually with ACTH treatment. Histologic examination of liver tissue revealed prominent hepatocellular vacuolisation. The trophic action of ACTH infusion was manifested by an increased adrenal gland weight and an enhanced cortisol response to a bolus ACTH injection given 1 day after the infusion ceased. Long-term infusion of ACTH resulted in haematologic, biochemical and morphologic changes resembling those observed in dogs with spontaneous pituitary-dependent hyperadrenocorticism.

Adrenocorticotropic Hormone↗