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PubMed1990

Effect of ACTH on VIP and galanin release from the pituitary.

The effect of adrenocorticotropin (ACTH) on the release of four regulatory peptides from the anterior pituitary of male rats has been studied using an in vitro perfusion system. Quartered anterior pituitaries from male adult Wistar rats were perfused with buffer containing different concentrations of ACTH and, subsequently, 56 mM KCl. Fractions of 1.5 ml were collected at 3 min intervals and analyzed for vasoactive intestinal peptide (VIP), galanin, 7B2, and substance P, using specific radioimmunoassays. Concentrations of 0.02, 0.1, 0.2, and 0.4 microM ACTH produced increases of 117 +/- 50%, 155 +/- 90%, 163 +/- 14%, and 161 +/- 3% (mean + SE), respectively, of basal release of VIP (P less than 0.001). However, concentrations of 1 microM and 2 microM ACTH suppressed VIP release to 74 +/- 6% and 47 +/- 4%, respectively, compared to basal release (P less than 0.001). Results for galanin release were similar: concentrations of 0.02, 0.1, 0.2, and 0.4 microM ACTH increased galanin release to 129 +/- 4%, 136 +/- 8%, 143 +/- 9%, and 133 +/- 9% of basal release (P less than 0.001) and 1 and 2 microM ACTH provoked a suppression of 52 +/- 7% and 50 +/- 13%, respectively, compared with basal release (P less than 0.001). Doses of ACTH that altered the secretion of VIP and galanin had no effect on 7B2 and substance P release. These results demonstrate that ACTH causes a release of pituitary VIP and galanin in vitro and, moreover, that this is a biphasic phenomenon.

Adrenocorticotropic Hormone↗
PubMed1975

The role of ACTH and adrenal glucocorticoids in the salt appetite of wild rabbits (Oryctolagus cuniculus (L)).

The selective appetites of wild rabbits for 500 mEq/1 solutions of NaC1, KC1, MgC1(2), and CaC1(2) were studied in intact and adrenalectomized rabbits during daily treatment with either 4 IU long acting ACTH, 1.0 or 2.5 mg cortisol acetate, or 2.5 mg corticosterone. The animals were individually caged and external sodium balances performed. In intact rabbits, cortisol or corticosterone produced a significant stimulation of NaC1 appetite. The response to concurrent dosage of cortisol and corticosterone was less than half of that obtained with ACTH which produced a comparable alteration of blood glucocorticoid levels but a 10-fold increase in NaC1 intake. CaC1(2) intake was increased in intact rabbits by cortisol treatment but not by corticosterone or ACTH. Adrenalectomized rabbits maintained on daily steroid replacement therapy of 0.1 mg deoxycorticosterone acetate and 0.75 mg cortisone acetate showed a normal pattern of electolyte, food, and water intake. Under these conditions ACTH produced a 4-fold increase in NaC1 intake. Further addition of cortisol and corticosterone to steroid replacement therapy produced an increase in NaC1 intake comparable to their effect on normal rabbits. Thereupon supplementation with ACTH resulted in an increase to a level at least as great as that found in ACTH treated, normal rabbits. The effects of ACTH and glucocorticoids on NaC1 appetite were synergistic. Sodium balance showed that increases in NaC1 intake were not the result of the treatment initially producing a body sodium deficit, which was then corrected by increased intake. The results provide further evidence for the hypothesis that NaC1 appetite may be hormonally regulated, and demonstrate that ACTH is capable of stimulating NaC1 intake by a previously unsuspected non-adrenal pathway.

Adrenalectomy↗
PubMed1998

A regulatory loop between the hypothalamo-pituitary-adrenal (HPA) axis and circulating leptin: a physiological role of ACTH.

The product of the ob/ob gene, leptin, is known to be able to exert a modulator, role on HPA axis function. The aim of the present study was to determine whether endogenous ACTH and glucocorticoids exert any regulatory effect on leptin secretion. For this purpose bilaterally adrenalectomized (ADX) or sham operated (Sham) adult male rats were implanted with an indwelling i.v. catheter. A subgroup of ADX animals received, at the same time of surgery, a s.c. corticosterone (B) pellet (75 mg) (ADX+B). All animals were subjected to experimental designs 7 days after surgery. Our results indicate, as expected, that 7-day ADX animals have several fold increased basal ACTH plasma levels and non detectable circulating B, whereas ADX+B rats showed basal plasma ACTH levels in the range of Sham values and plasma B concentrations of about 5 microg/dl. Interestingly, basal plasma leptin levels were significantly (P < 0.05) decreased by 7 days post ADX, and B replacement therapy (ADX+B) restored circulating leptin to Sham levels. Acute dexamethasone (Dxmn, 30 microg/kg body weight, i.v.) treatment induced a very rapid decrease in plasma ACTH concentrations in both Sham and ADX rats, as well as a decrease in plasma B levels in Sham rats. Interestingly, Dxm test had no effect on plasma leptin levels in Sham animals; however, in ADX rats, the synthetic glucocorticoid increased plasma leptin concentrations, restoring the levels observed in Sham rats. This effect occurred at the same time when plasma ACTH levels were decreasing toward basal Sham values. These results clearly indicate that, beside the known effects of leptin on HPA axis function, circulating ACTH and glucocorticoid are able to modulate leptin secretion in plasma. The lack of circulating glucocorticoid and/or increased plasma ACTH concentrations, are responsible for decreasing leptin output, whereas decreased plasma ACTH concentrations allow an increase of leptin secretion in blood. Our data strongly support the existence of a closed, bi-directional, circuit between HPA axis function and adipose tissue metabolism. They further indicate the physiological relevance of different types of stress associated with many phenotypes of obesity.

Adrenalectomy↗
PubMed1975

Inhibition of ACTH response to oral and intravenous metyrapone by antiserotoninergic treatment in man.

Plasma ACTH levels after oral and iv metyrapone administration were studied in 7 and 5 healthy women respectively both under basal conditions and after a 4-day treatment with metergoline, a specific antiserotoninergic agent. In 3 additional women, the effects of methysergide, another antiserotoninergic drug, on the plasma ACTH rise induced by oral metyrapone, were evaluated. A significant lowering of the plasma ACTH levels attained after either oral or iv metyrapone was observed following metergoline administration: 149+/-64.3 vs 239+/-49.1 pg/ml (mean peak values), P less than 0.05 in the oral test and 331+/-19.7 vs 221+/-19.5 pg/ml, P less than 0.02 in the iv test. The fall of plasma cortisol caused by metyrapone was comparable before and after the antiserotoninergic treatment. An interference of metergoline in the ACTH radioimmunoassay was also excluded. After metergoline administration, a slight reduction in the baseline plasma ACTH values was noted: 79+/-7.7 vs 67+/-7.7 pg/ml (NS). A decrease, however not statistically significant, of the metyrapone-induced plasma ACTH elevation occured after methysergide administration: 421+/-150.7 vs 344+/-135.1 pg/ml. These results can be interpreted as indicating that antiserotoninergic treatment caused an inhibition of hypophysial ACTH release in response to metyrapone. Caution is recommended, however, before concluding, on the basis of these findings, that serotonin as such plays a physiological stimulating role on ACTH secretion.

Administration, Oral↗
PubMed1976

The effect of administered ACTH on aldosterone metabolism and secretion.

To determine better the overall regulation of aldosterone by ACTH, the effect of administered ACTH on the aldosterone metabolic clearance rate (MCR), the excretion rates of tetrahydroaldosterone (THAldo), and the acid-labile conjugate (ALC) of aldosterone were studied in healthy male volunteers on a sodium intake in excess of 200 mEq/day. In 7 subjects, the aldosterone MCR increased significantly on the third day of ACTH treatment, as did the excretion of THAldo, but there was a decrease in the excretion of the ALC. One subject receiving ACTH for 6 days showed a steady increase in the aldosterone MCR on days 3 and 6 of treatment. In 2 of 3 subjects receiving ACTH treatment for 3-4 days, plasma aldosterone levels and plasma renin activity showed little change, whereas in 1 subject, both plasma aldosterone and plasma renin activity became suppressed. During ACTH administration there was a sustained increase in the excretion of THAldo, a metabolite formed in the liver, (in contrast to a decreasing excretion of the ALC which is made principally in the kidneys) which suggests that the increased aldosterone metabolism in response to ACTH occurred in the liver. Measurements made of the excretion of THAldo show that the ACTH stimulatory effect on aldosterone secretion may not be as transient as previously reported.

Adrenocorticotropic Hormone↗
PubMed1977

Plasma ACTH and cortisol responses to TRF, vasopressin or hypoglycemia in cushing's disease and nelson's syndrome.

The response of plasma ACTH and/or cortisol concentrations to thyrotropin-releasing-factor (TRF), vasopressin, and insulin administration was determined in 5 patients with Nelson's syndrome and 12 patients with untreated Cushing's disease. TRF administration was associated with a mean increment of 267 pg/ml in plasma ACTH concentrations in patients with Nelson's syndrome, and of 42 pg/ml in patients with Cushing's disease. The increment in plasma cortisol concentrations in the latter group was 12 mug%. No ACTH or cortisol response was observed in normal subjects. Patients with Cushing's disease or Nelson's syndrome exhibited significantly greater increments in plasma ACTH concentrations in response to vasopressin administration (P less than .05, P less than .02 respectively) than did normal subjects; the increment in cortisol concentration was also greater, (P less than .05), in patients with Cushing's disease than in normal subjects. No significant difference was present between patients with Cushing's disease and Nelson's syndrome with regard to the magnitude of the ACTH response to vasopressin administration. In contrast, the increment in plasma cortisol and plasma ACTH concentrations following insulin induced hypoglycemia was significantly less in patients with Cushing's disease than seen in normal subjects, (P less than .001, P less than .05 respectively); while this stimulus was associated with a significantly greater increment in plasma ACTH concentrations in patients with Nelson's syndrome as compared to that seen in normal subjects, (P less than .01) and in patients with Cushing's disease (P less than .01). These findings indicate that pituitary function in patients with Nelson's syndrome is not autonomous and suggest the possibility that altered central nervous regulatory mechanism might play a role in the etiology of the pituitary tumors which are frequently associated with this syndrome. The TRF induced rise in plasm cortisol and ACTH concentrations in patients with Cushing's disease and Nelson's syndrome suggests the possibility of altered hypothalamic or pituitary receptors in such patients.

Adolescent↗
PubMed2001

Increases in plasma ACTH and cortisol after hypertonic saline infusion in patients with central diabetes insipidus.

To clarify the mechanism for the potentiation of CRH-induced ACTH response by the infusion of hypertonic saline, we investigated changes in plasma ACTH concentration after infusion of 5% hypertonic saline in five patients with untreated central diabetes insipidus (DI). Basal levels of plasma ACTH and cortisol in the DI group were not significantly different from those in normal control subjects. The infusion of hypertonic saline produced an increase in plasma arginine vasopressin (AVP) in controls, but did not elevate ACTH. However, in patients with DI, the plasma AVP concentration did not change, but circulating ACTH increased 3.6-fold (7.7 +/- 1.5 to 23.0 +/- 2.7 pmol/liter; P < 0.01), and plasma cortisol also increased significantly (298 +/- 99 to 538 +/- 124 nmol/liter; P < 0.05). Moreover, a positive correlation was observed between plasma ACTH and osmolality (r = 0.72; P < 0.005). These results indicate that ACTH secretion in DI patients is regulated by a mechanism distinct from that in healthy subjects. It seems possible that the increase in plasma osmolality promotes ACTH secretion in DI patients through AVP and/or urocortin via the hypophyseal portal system, independent of the AVP secretion from magnocellular neurons.

Adrenocorticotropic Hormone↗
PubMed2002

Variable ACTH-stimulated 17-hydroxyprogesterone values in 21-hydroxylase deficiency carriers are not related to the different CYP21 gene mutations.

The currently used cutoff level for ACTH-stimulated 17- hydroxyprogesterone (17OHP) for the diagnosis of the nonclassical (NC) form of 21-hydroxylase deficiency (21OHD), established before molecular studies, is based on the mean + 2 SD of 17OHP levels of obligate heterozygotes. However, carriers of CYP21 mutations present variable ACTH-stimulated 17OHP levels, ranging from normal values up to 30 nmol/liter. The aim of this study was to determine whether ACTH-stimulated 17OHP levels in obligate carriers for 21OHD would be correlated with the impairment of the enzyme activity caused by these mutations, which would affect the 17OHP cutoff level for the diagnosis of the NC form. Fifty-nine parents of patients with the classical and NC forms of 21OHD had their DNA screened for the mutations found in the index case and were divided into three mutation groups according to the impairment of enzyme activity (A = 0%, B = 3%, and C > 20%). All parents carried mutations in one allele (29 of group A, 9 of group B, and 21 of group C). Blood samples were collected at baseline condition and 60 min after ACTH (250 microg i.v.) to measure 17OHP levels. The levels among groups A, B, and C were compared using the Kruskall Wallis test. ACTH-stimulated 17OHP levels identified 39% of the carriers (9 in group A, 2 in group B and 12 in group C). The mean +/- SD basal 17OHP levels in groups A, B, and C were: 2.94 +/- 1.89, 1.77 +/- 0.81 and 3.90 +/- 2.43 nmol/liter, respectively (P > 0.05) and for ACTH-stimulated levels were 12.6 +/- 7.2, 13.2 +/- 12.9 and 16.8 +/- 7.8 nmol/liter, respectively (P > 0.05). Two carriers presented ACTH-stimulated 17OHP levels between 30 and 45 nmol/liter and their entire CYP21 sequencing revealed only one mutation in heterozygous state indicating that the current cutoff level might overestimate the diagnosis of the NC form. We conclude that the variable ACTH-stimulated 17-OHP levels in carriers are not related to CYP21 gene mutations with different impairment of enzyme activity.

17-alpha-Hydroxyprogesterone↗
PubMed2002

Identification of two novel ACTH-responsive genes encoding manganese-dependent superoxide dismutase (SOD2) and the zinc finger protein TIS11b [tetradecanoyl phorbol acetate (TPA)-inducible sequence 11b].

ACTH is the major trophic factor regulating and maintaining adrenocortical function, affecting such diverse processes as steroidogenesis, cell proliferation, cell migration, and cell survival. We used differential display RT-PCR to identify genes that are rapidly induced by ACTH in the bovine adrenal cortex. Of 42 PCR products differentially amplified from primary cultures of bovine adrenocortical cells treated with 10 nM ACTH, six identified mRNAs that were confirmed by Northern blot analysis to be induced by ACTH. Four of these amplicons encoded noninformative repetitive sequences. Of the other two sequenced amplicons, one encoded a partial sequence for mitochondrial manganese-dependent superoxide dismutase (SOD2), an enzyme that is likely to protect adrenocortical cells from the cytotoxic effects of radical oxygen species generated during steroid biosynthesis. The second was identified as TIS11b (phorbol-12-myristate-13-acetate-inducible sequence 11b)/ERF-1/cMG, a member of the CCCH double-zinc finger protein family. SOD2 induction by ACTH was independent of extracellular steroid concentration or oxidative stress. SOD2 and TIS11b mRNA expressions were rapidly induced by ACTH, reaching a maximal level after 8 h and 3 h of treatment, respectively. These ACTH effects were mimicked by forskolin but appeared independent of cortisol secretion. Upon ACTH treatment, induction of TIS11b expression closely followed the previously characterized peak of vascular endothelial growth factor (VEGF) expression. Transfection of a TIS11b expression plasmid into 3T3 fibroblasts induced a decrease in the expression of a reporter gene placed upstream of the VEGF 3'-untranslated region, indicating that TIS11b may be an important regulator of VEGF expression through interaction with its 3'-untranslated region.

Adrenal Cortex↗
PubMed1986

Activities of ACTH-potentiating substances isolated from rat serum on steroidogenesis in isolated rat adrenal cells.

Peptides that potentiate the response of adrenal cells to ACTH1-24 were isolated from rat serum. ACTH-potentiating activity was found in fractions of 9,000-40,000 in molecular weight (APS-Fr) and of smaller molecular weight (SM-Fr) on Sephadex G-100 gel filtration of the serum extract. The peptides were isolated from APS-Fr by preparative acid polyacrylamide gel electrophoresis and named d1, d, d2, e, f and g. Their molecular weights, estimated by Sephadex G-75 gel filtration, were 41,000, 33,000, 24,000, 17,500, 17,500 and 16,000, respectively. All of these peptides were glycopeptides. The isoelectric point of peptide d was 8.45 and some of the others, such as f and g, were more basic. Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis revealed that these peptides were decomposed into various fragments. ACTH-potentiating activity was highest in peptide d1 and lowest in peptide e. The maximum activity of peptide d was observed at 3 X 10(-8) M when steroidogenesis was induced by 9 X 10(-12) M ACTH1-24. While these peptides did not show any ACTH-like activity at any stage of isolation, the fractions of these peptides eluted from a Sephadex G-75 column showed more or less ACTH-like activity. These peptides therefore seemed to possess latent ACTH-like activity. The molecular weight of SM-Fr was smaller than ACTH1-24. The ACTH-potentiating activity of SM-Fr was low, and SM-Fr did not show any ACTH-like activity. SM-Fr therefore seems to be the smallest structure which has ACTH-potentiating activity. The similarity of these peptides to proopiomelanocortin-related substances was discussed.

Adrenal Cortex Hormones↗
PubMed1999

Effects of peripheral blood polymorphonuclear leukocyte function and blood components in Japanese black steers administered ACTH in a cold environment.

An examination of the effects of artificial stress induced by adrenocorticotropin (ACTH) on total and differential leukocyte counts, plasma cortisol levels, metabolic profiles and peripheral blood polymorphonuclear leukocyte (PMN) function was performed on Japanese Black steers kept in a cold environment, with the following regimes; 1) -5 degrees C x ACTH (100 IU/day for 3 days), 2) 0 degrees C x ACTH, 3) 15 degrees C x ACTH and 4) 15 degrees C x PBS. Blood samples were collected before and at 1, 2, 24, 48, 72 and 96 hr prior to the application of the stressor. The plasma cortisol level was found to greatly increase at one hr after the first treatment of ACTH, particularly so in animals exposed to -5 degrees C. Total leukocytes (-5 degrees C and 0 degrees C experiments, respectively), the monocytes (-5 degrees C), neutrophils and eosinophils (-5 degrees C, 0 degrees C and 15 degrees C, respectively) obviously increased just after the first administration, although lymphocyte counts at -5 degrees C were inversely related to those described above. All of these tendencies were augmented by the cold environment except for eosinophils. The chemiluminescent (CL) response of PMN decreased in the ACTH-administered steers at an early stage of post-administration, however, it tended to recover from the lower-than-base value in the cold-affected steers. ACTH administration resulted in higher plasma glucose (Glu) compared to a control, although only steers housed at -5 degrees C evidently showed lower plasma inorganic phosphorus (IP). No abnormal serum acute phase protein, or immunosuppressor, was noted. ACTH thus appears not only to promote physiological reactions but also to temporarily suppress PMN cellular immune function in Japanese Black steers. Although, a cold environment rapidly restored the CL activity to over the pre-administrational value, suggesting that a vital response was activated by crymo-stimuli.

Adrenocorticotropic Hormone↗
PubMed1987

[Diurnal variation and responses of corticoids to dexamethasone and ACTH before and after adrenal surgery in primary aldosteronism].

We studied diurnal variation and the responses of plasma corticoids to dexamethasone and ACTH before and after adrenal surgery in 11 patients with primary aldosteronism. Diurnal variation of plasma corticoids was examined in all cases. Before adrenal surgery, plasma aldosterone (Ald) was higher at all times, deoxycorticosterone (DOC) was high value at 5:00 and then normal value, 11-deoxycortisol (S) was high value at 5:00 and 9:00, thereafter normal value, while corticosterone (B) and cortisol (F) were almost normal value at all times. The circadian rhythm was observed in these corticoids. Dexamethasone (2 mg/day) was administered to 8 patients for 10 days. Plasma Ald and DOC were significantly suppressed only at 5:00, while B, S and F almost suppressed at all times. After dexa suppression, the circadian rhythm of Ald still observed, while the diurnal variation of the other corticoids was even. ACTH (1 microgram) was injected intravenously to 9 patients. Responses of DOC, B and Ald were higher, and of S and F were almost normal. Diurnal variation of plasma corticoids was observed after 1 month of adrenal surgery. Ald was lower, the other corticoids were normal values. ACTH (1 microgram) was injected to the same case before surgery. Responses of these corticoids to ACTH were slightly lower. Contents of Ald in adenoma tissues were higher than those in adjacent and normal adrenal tissues, and the contents of the other corticoids in adenoma tissue were almost normal value. As these results showed, before surgery these corticoids were secreted from adenoma without ACTH, although these were responsible to ACTH, and the presence of regulative factor of circadian rhythm except ACTH was suggested. After surgery, not only the responses to ACTH of mineralocorticoids but these of glucocorticoids decreased.

Adrenal Cortex Hormones↗
PubMed1990

[Prostaglandin D2-endogenous regulator of physiological sleep-inhibited CRF-induced ACTH secretion from rat anterior pituitary cells].

Delta sleep-inducing peptide (DSIP) is described as being an endogenous sleep factor. This DSIP inhibits ACTH release induced by CRF from rat anterior pituitary tissue. Prostaglandin D2 (PGD2) is regarded as another endogenous sleep factor. However, little information has been accumulated concerning the involvement of PGD2 in the regulation of hormone secretion from the anterior pituitary. It was, therefore, interesting to observe the effect of PGD2 on ACTH release from rat anterior pituitary cells. Rat anterior pituitary cells were obtained by enzymatic digestion of the pituitary gland of male Wister rats. The cell pellet was suspended in Hank's balanced salt solution containing 0.1% BSA and distributed in a 800 microliter aliquot to 12 x 75mm glass tubes. The samples were preincubated for 90 min. in a 37 degrees C waterbath under 5% CO2/95% O2. After preincubation, aliquots of various concentrations of CRF, PGD2 and PGE2 were added in a 100 microliter volume and incubated for 4 hr. ACTH in the incubation medium was determined by radioimmunoassay. 0.01-1.0nM CRF significantly increased the ACTH release from rat anterior pituitary cells in a dose dependent manner. Each concentration of 0.1, 1, 2nM PGD2 or PGE2 had no effect on basal ACTH levels. 2nM PGD2 showed a significant inhibition of the CRF-induced ACTH secretion from rat anterior pituitary cells. Similarly, 2nM PGE2 significantly inhibited the CRF-induced ACTH release from rat anterior pituitary cells. The magnitude of the inhibitory effect of PGE2 was slightly higher than that of PGD2. From these results, we concluded that PGD2 inhibited CRF-induced ACTH secretion at the level of pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

[A case of unilateral primary adrenal nodular hyperplasia with elevated plasma adrenocorticotropin (ACTH)].

A 57-year-old woman was admitted to our hospital with occipital headache and nausea. She had severe hypertension (192/122mmHg), hypokalemia (2.8mEq/l) and fasting hyperglycemia (127 mg/dl). Further examination revealed elevated plasma ACTH (124pg/ml) and cortisol (26.5 mu g/dl) with a lack of diurnal rhythm. Plasma ACTH or cortisol did not increase by injection of corticotropin releasing hormone (CRH). Rapid ACTH test resulted in an exaggerated response of plasma cortisol. Abdominal MRI scan showed a left adrenal tumor. Since the bilateral adrenal venous blood sampling revealed a significant increase of cortisol on the left, left adrenalectomy was performed. Histological examination of the resected adrenal gland revealed marked cortical hyperplasia. Postoperative investigations revealed that despite a small dose of steroid replacement for only 20 days, plasma ACTH level was decreased for a period of 6 months. Both plasma ACTH and cortisol increased by a CRH injection 38 days after surgery. CRH test during bilateral inferior petrosal sinus sampling indicated that this patient had no functioning pituitary tumor. Although the exact mechanism of high plasma ACTH level in this case was unknown, these findings suggest that any substance secreted from primary adrenal nodular hyperplasia adrenal nodular hyperplasia may stimulate pituitary ACTH production. This is a very rare case of Cushing's syndrome due to unilateral primary adrenal nodular hyperplasia with elevated plasma ACTH.

Adrenal Glands↗
PubMed2002

Comparison of ACTH secretion in Cushing's adenoma and clinically silent corticotroph adenoma by cell immunoblot assay.

Immunocytochemical staining and cell immunoblot assay (CIBA) were performed in adenoma tissue from five patients with Cushing's disease and three patients with clinically silent corticotroph adenomas. All five patients with Cushing's disease showed hypersecretion of ACTH (130, 190, 331, 120, and 130 pg/ml), high levels of serum cortisol (26.6-44.0 micrograms/dl), and symptoms of Cushing's disease. All three patients with silent corticotroph adenoma showed hypersecretion of ACTH (110, 140, and 160 pg/ml) and normal levels of serum cortisol (11.4-26.8 micrograms/dl). The size of the pituitary adenoma on magnetic resonance imaging was smaller in patients with Cushing's disease (mean 8.2 mm) than in patients with silent corticotroph adenoma (mean 26.7 mm) (p = 0.001). Transsphenoidal surgery was performed to totally resect the adenoma tissue. Immunostaining for ACTH showed diffuse ACTH-immunopositive cells in all eight adenomas. CIBA technique showed a good correlation between percentage of ACTH-immunopositive cells and level of plasma ACTH in patients with Cushing's disease but no correlation between the two parameters in patients with silent corticotroph adenoma. The percentage of ACTH-secreting cells and the amount of hormone secreted by a single cell are too low in silent corticotroph adenomas to cause an increase in plasma ACTH level corresponding to the large tumor size.

Adenoma↗
PubMed1979

Comparative study of cyclic AMP-generation system, steroid biosynthesis and lipid metabolism in vitro in ACTH responsive and unresponsive adrenal tumors.

The responses of the cyclic AMP-generation system and corticosteroids biosynthesis to ACTH and angiotensin II and cholesterol and other lipid contents in adrenal tissues were estimated in the in vitro experiments in 3 cases of Cushing's syndrome due to ACTH-responsive and unresponsive adenomas, one case of Cushing's disease (diffuse hyperplasia), one case of primary aldosteronism and one normal subject. The responses of cAMP accumulation and corticosteroids production to ACTH in in vitro studies were quite in good agreement with the in vivo responses of plasma cortisol by ACTH infusion test. The adenylate cyclase activity decreased and the phosphodiesterase activity increased in the case of hyperplasia and in one case of ACTH-responsive adenoma, whereas the basal cyclic AMP content was slightly more in ACTH-responsive adenoma and maximal in hyperplasia compared with that of the normal adrenal tissue. The characteristic features observed in ACTH-unresponsive adenoma were the largest amount of the basal corticosteroids production and esterified cholesterol content, and the lowest content cAMP. These results indicate that there was not always the consistent correlation between the cAMP-generation system, corticosteroids and aldosterone production, and conversion of cholesterol to pregnenolone by the stimulation of ACTH and angiotensin II in adrenal tumors.

Adenoma↗
PubMed1984

Effects of bromocriptine and cyproheptadine on basal and corticotropin-releasing factor (CRF)-induced ACTH release in a patient with Nelson's syndrome.

The effects of bromocriptine, a dopamine agonist, and cyproheptadine, a serotonin antagonist, on basal and corticotropin-releasing factor (CRF)-stimulated ACTH release were investigated in a 40-year-old female patient with Nelson's syndrome. Oral administration of either bromocriptine (2.5 mg) or cyproheptadine (8 mg) caused a marked drop in plasma ACTH levels. Intravenous administration of synthetic ovine (o) CRF (50 micrograms) produced an exaggerated response of plasma ACTH. Short-term (3-week) treatment with either bromocriptine (7.5 mg/day) or cyproheptadine (12 mg/day) resulted in a marked suppression of basal ACTH release. Furthermore, a blunted response of plasma ACTH to oCRF was observed after short-treatment with either drug. However, after a longer period of treatment with cyproheptadine (18-week), plasma ACTH levels rose again and hyperresponsiveness to oCRF was restored to the pretreatment levels. These data indicate that synthetic oCRF is a potent secretagogue for ACTH release in a patient with Nelson's syndrome. It is suggested that bromocriptine and cyproheptadine are effective drugs in reducing basal and CRF-stimulated ACTH release, possibly acting at the pituitary level in this case. However, the apparent refractoriness after chronic treatment with cyproheptadine may limit its therapeutic use in the present case.

Adrenocorticotropic Hormone↗
PubMed1981

Effect of meclastine, an H1-antihistamine, on plasma ACTH in adrenal insufficiency.

In order to evaluate the possible role of endogenous histamine in ACTH secretion we investigated the effect of the H1 antagonist meclastine on plasma ACTH in patients with ACTH hypersecretion. Seven patients with primary adrenal insufficiency (group 1) and 5 patients with ACTH dependent Cushing's syndrome (group 2) were given an iv infusion of meclastine (4.8 mg/90 min). In patients of group 2 plasma ACTH was unaffected by meclastine infusion. However, in patients of group 1 with intact steroid feedback meclastine was followed by a significant drop in plasma ACTH as compared with ACTH levels after saline infusion (46.0 +/- 4.6% vs 85.0 +/- 7.0%, P less than 0.01). These results suggest that histamine is involved in the control of ACTH secretion, possibly by stimulation of CRF release.

Addison Disease↗