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PubMed1997

Pulsatile secretion of alpha-MSH and the differential effects of dexamethasone and haloperidol on the secretion of alpha-MSH and ACTH in dogs.

This study was performed to determine whether, in the dog, there is at any time pulsatile release of alpha-MSH and whether secretion of ACTH from the pars intermedia (PI) contributes to the circulating concentrations of ACTH. The 24-h secretory profiles of alpha-MSH, ACTH, and cortisol were determined in eight dogs. Plasma samples were obtained at 10-min intervals via an indwelling jugular catheter during two 12-h periods. Pulsatile secretion of alpha-MSH was found in all dogs, with wide variations in peak height. Plasma alpha-MSH levels were usually low (mean 15 pmol/l), but brief, distinct periods of increased plasma alpha-MSH concentrations as high as 489 pmol/l were found. Analysis of pulse frequency revealed a mean of 4.75 significant alpha-MSH peaks/24 h. The highest alpha-MSH peaks were associated with definite changes in the plasma concentrations of ACTH. In separate studies, the influence of dexamethasone on the 6-h secretory profiles and on the haloperidol-stimulated secretion of alpha-MSH, ACTH, and cortisol was investigated. In these two studies, plasma ACTH was measured by a highly sensitive immunoradiometric assay. Dexamethasone pretreatment significantly suppressed the plasma concentrations of ACTH, cortisol, and alpha-MSH to 10.3%, 3.9%, and 74.6% respectively. Dexamethasone pretreatment also significantly reduced the haloperidol-stimulated secretion of ACTH and cortisol, but had no influence on the haloperidol-stimulated secretion of alpha-MSH. After the administration of haloperidol to the dexamethasone-pretreated dogs, there were small increases in the plasma concentrations of ACTH and cortisol, the latter being significant. These data demonstrate that alpha-MSH is secreted spontaneously in a pulsatile manner in the dog and suggest that the canine PI contributes to circulating ACTH concentrations.

Adrenocorticotropic Hormone↗
PubMed1999

Adrenocortical response to ACTH in Angora and Spanish goat wethers.

Angora goats do not cope well with stress compared with goats of other breeds. Our hypothesis that this involves subclinical primary hypoadrenocorticism associated with low cortisol release in response to ACTH stimulation was tested by measuring adrenocortical response (plasma cortisol) in six Spanish (37 +/- 2 kg BW) and six Angora wethers (39 +/- 3 kg BW) under simulated acute and chronic ACTH challenges. In Exp. 1 (acute ACTH challenge), wethers were dosed i.v. with high (2.5 IU/kg BW) or low (.4 IU/kg BW) quantities of ACTH. In Exp. 2 (chronic ACTH challenge), ACTH at the rate of .015 IU/(kg BW x min) or saline (.15 M NaCl) was infused i.v. at 15 mL/h for 6 h. The mean baseline plasma cortisol concentration before ACTH stimulation was similar (P > .05) between Angora and Spanish goats in Exp. 1 (averaged over days) and in Exp. 2. The cortisol concentration response area (ng/ (mL x min) x 10(-3)) above the baseline was similar (P > .05) between Angora and Spanish goats during low (7.6 +/- .5 and 9.0 +/- 1.7, respectively) and high (12.8 +/- 1.0 and 16.0 +/- 1.8, respectively) levels of acute ACTH challenge (Exp. 1) and during chronic ACTH challenge (45.1 +/- 5.9 and 41.8 +/- 7.3, respectively; Exp. 2). In conclusion, these data indicate that, under the conditions of this study, adrenocortical responsiveness to ACTH stimulation is not different between Angora and Spanish goat wethers and, thus, may not contribute to stress susceptibility in Angora goats.

Adrenal Cortex↗
PubMedDate not supplied

ACTH receptor mRNA in human adrenocortical tumors: overexpression in aldosteronomas.

We previously reported that ACTH receptor (ACTH-R) mRNA is expressed in cortisol-secreting adrenal tumors, with significant differences between adenomas and carcinomas. In order to complete the study we have now evaluated 11 aldosteronomas (APA), 14 non-hypersecreting adenomas, 2 androgen-secreting adenomas and 8 normal adrenal glands. The level of ACTH-R mRNA was evaluated by competitive RT-PCR using a non-homologous competitor. ACTH-R gene was expressed in all tissues. All APA showed highest ACTH-R mRNA levels. Despite signs of individual heterogeneity, the level of ACTH-R transcripts was reduced in carcinomas. Furthermore, no significant differences were observed among cortisol-secreting adenomas, non hypersecreting adenomas and controls. The results show that ACTH-R mRNA is expressed in all adrenocortical tumors. The overexpression of ACTH-R in APA supports the role of ACTH on aldosterone secretion in these tumors, as also suggested by the presence of a diurnal rhythm, the lack of response to Angiotensin II, upright posture and captopril administration. The low abundance of ACTH-R in carcinomas might be a useful molecular marker of malignancy even if some overlap between carcinomas and adenomas does exist.

Adenoma↗
PubMedDate not supplied

Glucose-induced secretion of ACTH-like products by rat pancreatic islets.

This work was performed to study the release of proopiomelanocortin (POMC)-derived peptides from isolated pancreatic islets and the effect of ACTH--a member of that peptide family--on insulin secretion. Islets were incubated with 3,3 and 16.6 mM glucose and insulin and ACTH-like products (ACTH-LP) were measured by radioimmunoassay. Glucose stimulated the simultaneous release of insulin and ACTH-LP, the ACTH-LP concentration being higher when assayed with an antibody reacting with the N-terminus of ACTH. However, the increment in this release in the presence of the higher glucose concentration was larger when measured with an antibody against the ACTH mid-portion. Thus, although the islets would release more of a smaller ACTH-LP, 16.6 mM glucose would selectively increase the release of peptides of larger molecular size. Islets incubated with different concentrations of synthetic ACTH (50-500 pg/ml) increased the release of insulin in a dose-dependent manner. These results suggest that the release of endogenous ACTH-LP could contribute to the paracrine regulation of insulin secretion.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

ACTH receptor distribution and modulation among murine mononuclear leukocyte populations.

Murine mononuclear leukocytes express adrenocorticotropin (ACTH) receptors that were recognized by a monospecific antiserum to the ACTH receptor on Y-1 adrenal cells. The antiserum was utilized in an immunofluorescence (IF) assay to characterize the distribution of ACTH receptors on resting murine mononuclear leukocyte populations. Forty-seven percent of spleen cells, 32% of lymph node cells, and 1% of thymocytes constitutively expressed ACTH receptors. Separation of lymphocytes into purified B cell and T cell populations, followed by IF analysis revealed that 47% of B cells and 23% of T cells possessed ACTH receptors. Helper T cells (CD4+ T cells) constituted the majority of ACTH receptor-positive T lymphocytes. Furthermore, 47% of resident peritoneal macrophages, purified by adherence to plastic, expressed ACTH receptors. The T-lymphocyte mitogen, concanavalin A, interferon gamma, and ACTH enhanced ACTH receptor expression. The differential distribution of ACTH receptor-positive cells among specific leukocyte populations explains in part why differential cellular responses are observed and implies important regulatory functions for these receptors in the generation or regulation of immune responses.

Adrenocorticotropic Hormone↗
PubMed2003

Selective venous sampling in diagnosing ACTH-dependent hypercortisolism.

PURPOSE: To evaluate the sensitivity of selective sampling from the inferior petrosal sinuses in the differential diagnosis of ACTH-dependent hypercortisolism with non-diagnostic pituitary imaging. MATERIALS AND METHODS: Between 1987 and 2001, 17 patients (14 women and 3 men, aged 18-63 years) with ACTH-dependent hypercortisolism and negative X-ray of the sellar region, underwent simultaneous bilateral sampling from the inferior petrosal sinuses with ACTH measurement, at baseline and after stimulation with CRH (100 micro i.v.). Baseline samplings were also carried out at the level of the infrarenal and suprarenal inferior vena cava, of the adrenal and suprahepatic veins, of the superior vena cava, of the jugular veins, and of a peripheral vein. A central/peripheral gradient >2 at baseline and/or one >3 after stimulation with CRH was considered indicative of the pituitary origin of ACTH. Bilateral femoral venous catheterization was performed in an angiographic room using 5-French introducers after local anaesthesia. Selective catheterization of the inferior petrosal sinuses was achieved with 100 cm-long, steam-bent (45 degrees) 5-French catheters, without lateral holes. RESULTS: Twelve patients exhibited ACTH central/ peripheral gradients indicating the pituitary origin of the hormonal hyperincretion; this was confirmed by surgical exploration of the hypophysis in 10 patients, whereas 2 refused surgery and were therefore "lost". Of the five patients without ACTH central/peripheral gradients, one had an adrenal metastasis from ACTH-secreting lung neoplasia (with ACTH gradient in the blood flowing back from the adrenal gland), one had a hepatic CRHoma (with high levels of CRH in the suprahepatic veins), whereas the origin of the hyperincretion remained indeterminate in three. CONCLUSIONS: Bilateral simultaneous selective sampling from the inferior petrosal sinuses for ACTH measurements proved to be highly sensitive and free of complications in the differential diagnosis of ACTH-dependent forms of hypercortisolism.

Adolescent↗
PubMed1991

ACTH-induced inhibition of the action of angiotensin II in bovine zona glomerulosa cells. A modulatory effect of cyclic AMP on the angiotensin II receptor.

Both angiotensin II and adrenocorticotropic hormone (ACTH) are well known to play a crucial role on the regulation of aldosterone production in adrenal glomerulosa cells. Recent observations suggest that the steroidogenic action of ACTH is mediated via the cAMP messenger system, whereas angiotensin II acts mainly through the phosphoinositide pathway. However, there have been no reports concerning the interaction between the cAMP messenger system activated by ACTH and the Ca2+ messenger system induced by angiotensin II. Both ACTH and angiotensin II simultaneously act on adrenal cells for regulating steroidogenesis under physiological conditions. Thus the present experiments were performed to examine the effect of ACTH on the action of angiotensin II by measuring angiotensin II receptor activity, cytosolic Ca2+ movement, and aldosterone production. The major findings of the present study are that short-term exposure to a high dose of ACTH (10(-7) M) inhibited 125I-angiotensin II binding to bovine adrenal glomerulosa cells, decreased the initial spike phase of [Ca2+]i induced by angiotensin II, and inhibition of angiotensin II-induced aldosterone production. Low dose of ACTH (10(-10) M), which did not increase cAMP formation, did not affect angiotensin II receptor activity. These studies have shown that angiotensin II receptors of bovine adrenal glomerulosa cells can be down-regulated by 1 mM dibutyryl cyclic AMP, as well as by effectors which are able to activate cAMP formation (10(-7) M ACTH and 10(-5) M forskolin). The rapid decrease in angiotensin II receptors induced by 10(-7)M ACTH was associated with a decreased steroidogenic responsiveness and a decreased rise in the [Ca2+]i response induced by angiotensin II. These studies show that the cAMP-dependent processes activated by ACTH have the capacity to interfere with signal transduction mechanisms initiated by receptors for angiotensin II.

Adrenocorticotropic Hormone↗
PubMed1990

Sex differences in adrenocortical structure and function. XXVIII. ACTH and corticosterone in intact, gonadectomised and gonadal hormone replaced rats.

Plasma ACTH and corticosterone (B) concentration, ACTH content in the anterior pituitary gland and B content in the adrenals were measured in intact, gonadectomised and testosterone or estradiol replaced rats. Plasma ACTH and B levels and adrenal B content were higher in female than male rats. Neither orchiectomy nor testosterone replacement had an effect on plasma ACTH and B concentration. Orchiectomy did not affect adrenal B content and decreased pituitary ACTH while testosterone significantly lowered ACTH and B content in studied glands. On the other hand ovariectomy did not change pituitary ACTH and adrenal B content and notably lowered concentrations of these hormones in the blood. Estradiol replacement resulted in an increase in plasma ACTH and B concentrations, an effect accompanied by a marked drop in pituitary ACTH and an increase in adrenal B. These findings indicate the distinct sex differences in basal plasma ACTH and B concentrations with higher values in female rats, an effect dependent on the stimulatory action of estradiol on pituitary-adrenocortical axis.

Adrenal Cortex↗
PubMed1982

Plasma cortisol response to exogenous ACTH in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia.

The plasma cortisol response to exogenous ACTH (ACTH stimulation test) was evaluated in 22 dogs with hyperadrenocorticism caused by adrenocortical neoplasia. The mean basal cortisol concentration (6.3 microgram/dl) was high, but 7 dogs had basal cortisol concentrations that were within normal range. Administration of exogenous ACTH increased the plasma cortisol concentrations in each dog. Normal post-ACTH cortisol concentrations were found in 9 (41%) of the 22 dogs; 13 (59%) had an exaggerated increase in cortisol concentrations after ACTH administration. In 9 of 13 dogs with carcinoma and in 4 of 9 with adenoma, the cortisol response was exaggerated. The mean post-ACTH cortisol concentration in the dogs with carcinoma was approximately 4 times that of the dogs with adenoma; the 7 dogs with the highest concentrations had carcinoma. Repeat studies were performed in 6 dogs 2 to 8 weeks after initial testing. In 5 of the 6 dogs, repeat testing yielded data of similar diagnostic significance. One dog, however, had an abnormally high post-ACTH cortisol concentration at initial evaluation, but had only a minimal response to ACTH administration, with a normal post-ACTH cortisol concentration, at time of resting. Although ACTH stimulation testing is useful in diagnosing hyperadrenocorticism, it can not reliably separate dogs with hyperfunction adrenocortical tumors from clinically normal dogs or from dogs with pituitary-dependent hyperadrenocorticism (bilateral adrenocortical hyperplasia).

Adenoma↗
PubMed1981

Concentrations of corticosteroids, leukocytes, and immunoglobulins in blood and milk after administration of ACTH to lactating dairy cattle: effects on phagocytosis of Staphylococcus aureus by polymorphonuclear leukocytes.

A study was conducted to determine relationships among plasma and milk corticosteroids, milk immunoglobulins, and phagocytosis of Staphylococcus aureus by polymorphonuclear leukocytes (PMN) isolated from milk of cows given injections of 0 (saline solution only), 100, and 200 IU of ACTH. Also determined were the effects of ACTH on mobilization of PMN into milk from the mammary gland irritated by infusion of 100 ml of saline solution containing 0.1% oyster glycogen. Cows (n = 10) were injected 6 times within a 48-hour period with 0, 100, or 200 IU of ACTH. Immediately before cows were given the 5th injection, 2 mammary quarters were infused with the saline-glycogen solution. Five hours after the 6th injection, milk from infused quarters was collected, and PMN were isolated, washed, and resuspended in autologous skimmed milk collected 5 hours after the 4th injection and before the udder was infused. Isolated PMN were incubated with S aureus and percentage of phagocytosis was determined. Concentrations of total corticosteroids in plasma and milk increased after cows were given injections of 100 and 200 IU of ACTH. The concentrations of IgA, IgG1, IgG2, IgM, and bovine serum albumin in milk after 4 injections of 0, 100, and 200 IU of ACTH were similar to preinjection (base line) concentrations. Injections of 100 and 200 IU of ACTH significantly increased the concentrations of total circulating leukocytes. Concentrations of leukocytes in milk tended to increased with increasing doses of ACTH, but the differences were not significant. Injection of 100 and 200 IU of ACTH reduced phagocytosis of S aureus by PMN. After 60 minutes of incubation, phagocytosis averaged 57% and 54%, respectively, for the ACTH treatments and 70% for controls (saline only). Results indicate that injections of ACTH that result in physiologic and pharmacologic plasma concentrations of corticosteroids inhibit phagocytosis. Impairment of phagocytosis appeared to be a direct effect of corticosteroid concentration o PMN and was not due to reduced concentrations of immunolobulins. These data indicate that reduced phagocytosis by PMN could be important in increased susceptibility to disease during stress in lactating dairy cows.

Adrenal Cortex Hormones↗
PubMedDate not supplied

[Molecular forms of pituitary and plasma ACTH in physiology and pathology].

Immunoreactive ACTH has been found in human pituitary and plasma under different molecular forms: Big ACTH, intermediate ACTH, ACTH 1-39 and fragments of ACTH. In the literature, there are some controversies especially regarding to the importance of Big ACTH in plasma and tissue. Big ACTH is absent or present in only low amounts in plasma and pituitary extracts from normal subjects. However, the proportion of Big ACTH is very high in tumor extracts and plasma obtained from patients with ectopic ACTH syndrome High concentrations of small ACTH fragments are also present in this syndrome.

Addison Disease↗
PubMed1993

[Clinical value of the various methods of ACTH determination].

We determined 293 plasma-ACTH levels out of 49 patients. In 12 patients with various pituitary diseases 168 samples were collected during a standardized pituitary stimulation test. For this purpose we used the following kits: the DYNOtest ACTH and LUMItest ACTH and Allegro HS-ACTH test. Additionally, morning ACTH levels were analyzed from 49 patients using Allegro HS ACTH test and DYNOtest ACTH. Regarding ACTH concentrations during pituitary stimulation the clinical usefulness of the 3 named tests were comparable. Pair differences of morning ACTH levels were not statistically significant. In a setting of a wide range of ACTH levels all 3 trials proved appropriate for making a diagnosis. Practicability of all 3 tests was similar. For all 3 methods incubation can be done overnight which saves time. Reagents can be reused when frozen immediately after reconstitution.

Adrenocorticotropic Hormone↗
PubMed1997

Effect of blood sampling and administration of ACTH on cortisol and progesterone levels in ovariectomized zebu cows (Bos indicus).

Four zebu cows were bilaterally ovariectomized through lateral laparotomy. Three months after ovariectomy, blood samples were collected by jugular venipuncture daily for 5 consecutive days prior to a single injection of ACTH to establish baseline concentrations of cortisol and progesterone. Baseline concentrations of cortisol and progesterone were 31 +/- 5 nmol/L and 0.3 +/- 0.01 nmol/L, respectively. On the day of ACTH treatment the cows were allowed to rest for 2 h to reduce the stress of cannulation before the sampling period started. Blood samples were collected every 30 min from 2 h before until 2 h after the injection of 6 micrograms ACTH and hourly between 2-6 h after ACTH injection. A significant increase was observed in cortisol secretion from 90 min before until 120 min after ACTH injection. No significant increase was observed in progesterone secretion before ACTH injection. After ACTH injection progesterone was significantly elevated for 120 min. Four weeks after the ACTH treatment the cows were cannulated again and blood samples were collected following the same bleeding schedule used during the ACTH experiment. Instead of ACTH a saline injection was given via the catheter. A significant increase in cortisol concentration was recorded 90 min before saline injection. This increase was not accompanied by an elevation in progesterone concentration. No significant changes were observed in cortisol and progesterone levels after saline injection. When cortisol was added to a plasma pool having a progesterone concentration of 0.3 nmol/L and a cortisol concentration of 25.4 nmol/L and assayed for progesterone in 2 different assays no increase in progesterone concentration was observed. We conclude that the adrenal glands can be an extra-ovarian source of progesterone during stress in Zebu cows.

Adrenocorticotropic Hormone↗
PubMed2003

The corticotrophin-releasing hormone test is the most reliable noninvasive method to differentiate pituitary from ectopic ACTH secretion in Cushing's syndrome.

OBJECTIVE: It has been reported previously that the paired interpretation of the corticotrophin-releasing hormone (CRH) test and the 8-mg dexamethasone suppression test (HDDST) could have higher diagnostic power than any single test in the differential diagnosis of ACTH-dependent Cushing's syndrome. This finding has not been confirmed thereafter in large series. The aim of the present study has been to assess the operating characteristics of either the CRH test or the overnight HDDST and also to evaluate the potential utility of combining the interpretation of both tests in the differential diagnosis of ACTH-dependent Cushing's syndrome. DESIGN AND PATIENTS: We have reviewed the medical records of 59 consecutive cases with ACTH-dependent Cushing's syndrome: 49 patients with proven Cushing's disease (CD) and 10 patients with proven ectopic ACTH syndrome (EAS). Univariate curves of the receiver operating characteristics (ROC) have been performed to define the best cut-off values, the sensitivity and the specificity for CRH and overnight HDDST. A comparison between the areas under the ROC curves has also been performed. RESULTS: For the CRH test, the point on the ROC curve closest to 1 corresponded to a value of ACTH percentage increment of 50%[sensitivity 86% (72.6-94.8) and specificity 90% (55.5-98.3)]. The best threshold for cortisol percentage (30%) increment gave inferior results [sensitivity 61% (45.5-75.6) and specificity 70% (34.8-93.0)]. For the HDDST, the point on the ROC curve closest to 1 corresponded to a value of cortisol decrease from the baseline of 50%[sensitivity 77% (62.7-88.5), specificity 60% (26.4-87.6)]. The area under the ROC curve of the ACTH percentage increment after CRH was significantly greater than the area under the diagonal [0.9 (0.7-1.0), P= 0.0001]. Conversely, the area under the cortisol percentage decrement after dexamethasone was not different from that obtained by chance [0.7 (0.5-0.9), P= ns]. The area under the ROC curve of CRH is significantly greater than that of overnight HDDST (P = 0.03). A correct diagnosis has been achieved by the CRH test in 86.5% of cases and by the HDDST in 73% (P = 0.06). The combination of both tests has given a correct diagnosis in a significantly lower percentage of cases than the CRH test alone (69%, P= 0.04). The bilateral inferior petrosal sinus sampling (BIPSS) has been performed in 29 patients (24 CD, five EAS) who had negative imaging and/or discordant results of the noninvasive tests. Considering the criterion of a central to peripheral ACTH ratio > 3 after CRH stimulation, a correct diagnosis was achieved in all cases. CONCLUSIONS: The present data suggest that the CRH is likely to be the most reliable noninvasive diagnostic procedure for the differential diagnosis of the ACTH-dependent Cushing's syndrome. The criterion for a diagnosis of EAS is an ACTH percentage increment lower than 50%. The use of a combination of tests is not recommended because it does not add valuable information and may even impair the outcome of the CRH test. Cases with discordant results in pituitary imaging and CRH test should undergo BIPSS. The validity of this approach, which is straightforward and easily applicable in clinical practice, should be verified in larger series.

ACTH Syndrome, Ectopic↗
PubMed1992

Mineralocorticoid excess and inhibition of 11 beta-hydroxysteroid dehydrogenase in patients with ectopic ACTH syndrome.

OBJECTIVE: 11 beta-Hydroxysteroid dehydrogenase protects renal mineralocorticoid receptors from cortisol by converting cortisol to inactive cortisone. We hypothesize that 11 beta-dehydrogenase is inhibited by ACTH, providing a mechanism whereby cortisol induces hypokalaemic alkalosis in ectopic ACTH syndrome. DESIGN/MEASUREMENTS: The principal sources of plasma cortisone were assessed by selective venous catheterization with measurement of cortisol and cortisone by radioimmunoassays. The effect of ACTH on peripheral plasma cortisol/cortisone ratio was assessed in healthy volunteers during circadian rhythm, insulin induced hypoglycaemia, and infusions with exogenous ACTH or cortisol. In patients with Cushing's syndrome plasma cortisol/cortisone ratios were related to plasma potassium, corticosterone, and 11-deoxycorticosterone concentrations. PATIENTS: Catheterization was performed in 24 patients with valvular or ischaemic heart disease. Cushing's syndrome patients included: 15 with pituitary adenoma; two with adrenal adenoma; and nine with ectopic ACTH secretion. RESULTS: Plasma cortisol/cortisone ratios were low in renal vein and high in hepatic vein. In healthy volunteers plasma cortisone increased during cortisol infusion but did not change with increases in endogenous or exogenous ACTH. Plasma cortisol/cortisone ratios were higher in ectopic ACTH syndrome than in other forms of Cushing's syndrome. However, the cortisol/cortisone ratio was no better a predictor of hypokalaemia than the levels of 11-deoxycorticosterone or corticosterone. CONCLUSIONS: Peripheral conversion of cortisol to cortisone occurs mainly in the kidney and is inhibited by ACTH. In ectopic ACTH syndrome the characteristic mineralocorticoid excess can be accounted for by a combination of increased secretion of cortisol, corticosterone and of 11-deoxycorticosterone and decreased inactivation of cortisol and corticosterone by 11 beta-dehydrogenase.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

The pituitary V3 vasopressin receptor and the corticotroph phenotype in ectopic ACTH syndrome.

Ectopic ACTH secretion occurs in highly differentiated and rather indolent tumors like bronchial carcinoids or, in contrast, in various types of aggressive and poorly differentiated neuroendocrine tumors. We explored this phenomenon using the recently cloned human pituitary V3 vasopressin receptor as an alternate molecular marker of the corticotroph phenotype. Expression of V3 receptor, corticotrophin releasing hormone (CRH) receptor, and proopiomelanocortin (POMC) genes was examined in tumors of pituitary and nonpituitary origin. A comparative RT-PCR approach revealed signals for both V3 receptor and CHR receptor mRNAs in 17 of 18 ACTH-secreting pituitary adenomas, and 6 of 6 normal pituitaries; in six growth hormone- or prolactin-secreting adenomas, a very faint V3 receptor signal was observed in three cases, and CRH receptor signal was undetected in all. Six of eight bronchial carcinoids responsible for the ectopic ACTH syndrome had both POMC and V3 receptor signals as high as those in ACTH-secreting pituitary adenomas; in contrast, no POMC signal and only a very faint V3 receptor signal were detected in six of eight nonsecreting bronchial carcinoids. Northern blot analysis showed V3 receptor mRNA of identical size in ACTH-secreting bronchial carcinoids and pituitary tumors. Other types of nonpituitary tumors responsible for ectopic ACTH syndrome presented much lower levels of both POMC and V3 receptor gene expression than those found in ACTH-secreting bronchial carcinoids. In contrast with the V3 receptor, CRH receptor mRNA was detected in the majority of neuroendocrine tumors irrespective of their POMC status. These results show that expression of the V3 receptor gene participates in the corticotroph phenotype. Its striking association with ACTH-secreting bronchial carcinoids defines a subset of nonpituitary tumors in which ectopic POMC gene expression is but one aspect of a wider process of corticotroph cell differentiation, and opens new possibilities of pharmacological investigations and even manipulations of this peculiar ACTH hypersecretory syndrome.

ACTH Syndrome, Ectopic↗
PubMed2004

An aberrant ACTH-producing ectopic pituitary adenoma in the sphenoid sinus.

A 32-year-old woman with an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma (EAPA) is presented. She had rapidly gained weight and suffered recurrent facial acne for a few years but lacked the typical Cushingoid features. Endocrine examinations revealed that her plasma ACTH was markedly high (196 to 280 pg/ml) without showing normal circadian rhythm and failed to respond to corticotropin-releasing hormone stimulation. Her cortisol levels ranged from 22 to 30 microg/dl throughout observation but low doses (1 and 2 mg) of dexamethasone failed to suppress either ACTH or cortisol level. Magnetic resonance imaging study revealed a 3-cm mass occupying the sphenoidal sinus with partial enhancement by gadolinium, which was separated from the normal pituitary in the sella region. The tumor resected by transsphenoidal surgery was histologically diagnosed as an ACTH-producing pituitary adenoma. After surgery her weight gain and acne remitted in accordance with decreases in plasma ACTH. Analysis of patient plasma by gel filtration method revealed the existence of big ACTH molecules eluted with a peak of authentic 1-39 ACTH, suggesting that this biologically less-active ACTH might be the reason why overt features of Cushing's syndrome failed to develop in this case. Although EAPA is clinically rare in parasellar disorders, the presence of ectopic pituitary adenoma should be considered in such cases showing ACTH hypersecretion without typical Cushingoid features.

ACTH Syndrome, Ectopic↗
PubMed1996

Interactions of ACTH and TGF beta on monocyte proliferation: implications for trauma and burn patients.

The purpose of this study was to try to elucidate a possible biobehavioral mechanism associated with decreased immune function in trauma patients by determining whether there is an interaction between the effects of ACTH, a stress hormone, and TGF beta, a cytokine, on peripheral blood lymphocyte proliferation. Peripheral mononuclear lymphocytes (PMLs) from healthy donors were preincubated with varying concentrations of ACTH for 24 hr, stimulated with concanavalin A and increasing concentrations of TGF beta, and incubated for 72 hr. Proliferation was assayed by tritiated thymidine incorporation. A parallel aliquot of PMLs were incubated in the presence of ACTH to determine the direct effect of ACTH on mononuclear cell TGF beta production. While harvested supernatant from cells incubated in the presence of ACTH did not contain any detectable TGF beta, ACTH as well as TGF beta were found to significantly decrease cellular proliferation independent of one another. An even greater decrease in cellular proliferation was found when both ACTH and TGF beta were used, compared to either ACTH or TGF beta alone. These results suggest a biobehavioral interaction between ACTH and TGF beta at the cellular level and that interactions to relieve stress may assist in improving function and recovery from trauma.

Adrenocorticotropic Hormone↗