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PubMed1982

[The changes of human plasma ACTH and immunoreactive beta-endorphin during spontaneous or oxytocics induced/maintained labor and delivery (author's transl)].

To evaluate the effects of oxytocics on ACTH and Immunoreactive (IR)-beta-endorphin release, concentrations of these hormones in the plasma of 22 women during spontaneous labor, 22 women in labor who had received oxytocin and 19 women in labor who had received PG.F2 alpha at the time of vaginal delivery, were measured. Maternal ACTH and IR-beta-endorphin concentrations were elevated during spontaneous or oxytocics induced/maintained labor and peaked immediately after delivery and decreased two hours later. There were significant correlations between ACTH and IR-beta-endorphin concentrations during spontaneous labor and delivery (r = 0.921, p less than 0.0001), as well as in oxytocin or PG.F2 alpha induced/maintained labor and delivery (r = 0.833, r = 0.916, p less than 0.0001, respectively). The concentrations of ACTH and IR-beta-endorphin during PG-F2 alpha infusion were slightly higher than those seen in the other two types of labor. However, there was no significant difference in the levels of ACTH and IR-beta-endorphin among the three types of labor. Simultaneous maternal and umbilical cord plasma samples were obtained in 25 cases at delivery. However, there was no significant correlation between ACTH or IR-beta-endorphin concentrations in paired samples. These results suggest that 1) IR-beta-endorphin is secreted in parallel with ACTH, into the peripheral blood by the maternal pituitary gland in response to the stress of labor during all types of labor and delivery; 2) there is no significant difference in the response of ACTH and IR-beta-endorphin between spontaneous and oxytocics induced/maintained labor and delivery: 3) ACTH and IR-beta-endorphin in cord blood are not of maternal origin.

Adrenocorticotropic Hormone↗
PubMed1983

Use of a low dose synthetic ACTH challenge test in normal and prednisone-treated dogs.

The utility of a low dose (1 microgram/kg) synthetic ACTH challenge test in detecting moderate reductions in adrenocortical sensitivity in dogs was examined. First, the adrenocortical responses to an intravenous bolus of either 1 microgram/kg or 0.25 mg per dog of synthetic ACTH were compared in two groups of normal dogs. While plasma cortisol concentrations were similar in both groups 60 minutes after ACTH injection, dogs given 0.25 mg ACTH showed continued elevations in plasma cortisol concentrations at 90 and 120 minutes after ACTH injection. Later, the dogs previously tested with the 1 microgram/kg ACTH challenge were given a single intramuscular dose of prednisone (2.2 mg/kg) and retested with 1 microgram/kg of ACTH one week later. Plasma cortisol levels were significantly reduced after ACTH injection in dogs previously given prednisone demonstrating that a single intramuscular prednisone dose causes detectable adrenocortical suppression one week after administration. The 1 microgram/kg synthetic ACTH challenge test provides a sensitive means for evaluating adrenocortical suppression in dogs.

Adrenal Cortex↗
PubMed1994

Evidence that ACTH secretion is regulated by serotonin2A/2C (5-HT2A/2C) receptors.

The present study characterized the serotonin (5-HT) receptor subtypes mediating adrenal corticotropic hormone (ACTH) and corticosterone responses to 5-HT agonists in conscious rats. The 5-HT2A/5-HT2C agonist (+/-(-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HC1 (DOI) increased plasma ACTH and corticosterone in a dose-dependent manner. The 5-HT2A/5-HT2C antagonist ritanserin (0.01 and 0.1 mg/kg sc) inhibited the DOI-induced increase in plasma ACTH, but not corticosterone. Low doses of spiperone (0.01 and 0.1 mg/kg sc) significantly reduced the ACTH response to DOI. Because spiperone has a higher affinity for 5-HT2A than 5-HT2C receptors, these data suggest that DOI stimulates ACTH secretion through 5-HT2A receptors. 5-methoxy-3-[1,2,3,4-tetrahydro-4-pyridinyl]-1H-indole (RU 24969) is a potent 5-HT1A/1B and moderate 5-HT2C agonist that also has been suggested to release 5-HT. However, p-chlorophenylalanine (PCPA) did not reduce the effect of RU 24969 on plasma ACTH, suggesting that RU 24969 only acts as a direct agonist. 6-methyl-1-[1-methylethyl]ergoline-8-carboxylic acid (LY53857) injected into the lateral cerebral ventricles (i.c.v.) inhibited the ACTH, but not corticosterone response to peripheral injection of RU 24969, suggesting that central 5-HT2A/2C receptors mediate the ACTH response. LY53857 injection (i.c.v.) also inhibited the effect of p-chloroamphetamine (i.c.v.) on plasma ACTH. However, the corticosterone response was not inhibited by LY53857, suggesting a distinct location of 5-HT receptors regulating corticosterone secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed2005

An extra-adrenal abdominal pheochromocytoma causing ectopic ACTH syndrome.

We report a 55-year-old woman with ectopic adrenocorticotropin (ACTH) secretion caused by extra-adrenal pheochromocytoma. The patient presented with a 6-month history of hypertension and diabetes mellitus. Her serum and urinary cortisol levels were extremely high and dexamethasone failed to suppress the cortisol secretion. Her plasma ACTH levels were also elevated (>300 pg/mL) and irresponsive to corticotropin-releasing hormone (CRH) or metyrapone administration. Gel filtration analysis of the patient's plasma detected the existence of large molecular weight ACTH being eluted with a major peak of authentic 1-39 ACTH. Abdominal computed tomographic scan and magnetic resonance imaging revealed a 5-cm paraganglioma located underneath the left kidney, in which (123)I-MIBG tracer specifically accumulated. Bilateral adrenal glands were diffusely enlarged. After surgical removal of the paraganglioma, the patient's clinical symptoms improved and biochemistry normalized including plasma ACTH, urinary free cortisol, and urinary catecholamines. Subsequent histologic evaluation of the transected paranglioma tissue revealed ACTH, synaptin, and chromogranin-A histologically immunostaining. Culture of primary cells collected from the resected paraganglioma demonstrated of in vitro production of ACTH, noradrenaline, and adrenaline. This is the first report of ectopic ACTH syndrome induced by an extra-adrenal abdominal paraganglioma.

ACTH Syndrome, Ectopic↗
PubMed1998

Effect of hypercortisolism and ACTH on the metabolism of cortisol.

The effects of hypercortisolemia and ACTH on the metabolism of cortisol in congenital adrenal hyperplasia, Cushing's syndrome, and exogenous ACTH and cortisol administration were investigated by analysis of the respective urinary tetrahydro-metabolites of cortisol (THF and aTHF) and cortisone (THE) by capillary gas chromatography. The results for the patients with congenital adrenal hyperplasia establish that ACTH hypersecretion in the absence of an associated marked elevation of plasma cortisol does not cause inhibition of the 11beta-OHSD enzyme. In contrast elevated plasma cortisol levels (adrenal adenoma or intravenous cortisol administration) in the presence of suppressed ACTH secretion leads to significant inhibition of the peripheral conversion of cortisol to cortisone. The latter results are equivalent to the mode of cortisol metabolism noted during clinical states of ACTH hypersecretion and hypercortisolemia (Cushing's disease, ectopic ACTH syndrome and ACTH administration). The overall findings provide convincing evidence that ACTH hypersecretion is not associated with specific in vivo inhibition of 11beta-OHSD enzyme activity.

ACTH Syndrome, Ectopic↗
PubMedDate not supplied

Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion.

Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation.

ACTH Syndrome, Ectopic↗
PubMed1983

Pro-opiocortin related peptides in human pituitary and ectopic ACTH secreting tumours.

Basal and stimulated secretion of N-terminal pro-opiocortin (Pro-gamma-MSH), ACTH and LPH from seven pituitary and three ectopic ACTH secreting tumours have been studied in vitro using a perfused isolated cell system. The peptides were shown to be released concomitantly and in equimolar amounts. The pituitary tumours responded to stimulation with rat stalk median eminence extracts (SME) and synthetic AVP. However, peptide release from the ectopic tumours, although pulsatile, remained autonomous. Prior to surgery, gel-chromatographic profiles of plasma immunoreactive ACTH showed only one peak, which eluted in the position of 1-39 ACTH, in patients with the pituitary tumours, but there was a second peak of large molecular weight ACTH present in the plasma from those with the ectopic ACTH syndrome. This second form of ACTH could not be detected in any of the tumour cell column effluents. An eighth pituitary tumour was atypical, in its unusually large size, clinically aggressive nature and spectrum of peptide release. Although peptide release in response to stimulation with SME was similar to that observed with the other pituitary tumours, the chromatography of the plasma ACTH resembled the ectopic plasma pattern, showing two peaks of immunoreactivity.

ACTH Syndrome, Ectopic↗
PubMed1989

Central and peripheral ACTH and cortisol levels in anorexia nervosa and bulimia.

To explore the relationship of central and peripheral adrenocorticotropic hormone (ACTH, or corticotropin) levels to hypothalamo-pituitary-adrenal axis dysfunction in patients with eating disorders, levels of cerebrospinal fluid (CSF) and plasma ACTH, cortisol, and 24-hour urinary free cortisol were measured in 16 patients with anorexia nervosa (60% +/- 1.1% of ideal body weight), 14 patients with bulimia (93.2% +/- 4.6% of ideal body weight), and 11 healthy age-matched women volunteers. The CSF, plasma, and urinary free cortisol levels were elevated in underweight anorexic patients and showed declines following weight recovery. Cortisol-binding globulin levels were similar in anorexics and controls. In contrast, underweight anorexics showed low CSF ACTH levels that returned to normal following weight recovery, and their plasma ACTH levels were normal. On hospital admission, bulimic patients demonstrated normal ACTH and cortisol levels. After their abstinence from binge-purge episodes, the CSF ACTH levels decreased significantly. Positive relationships were found among CSF, plasma, and urinary cortisol levels, and inverse relationships were seen between cortisol measures and CSF ACTH levels in patients with eating disorders. Secretion of ACTH into the CSF may respond to feedback by cortisol or, alternatively, may be suppressed by the hypersecretion of corticotropin-releasing hormone, leading to the depletion of the pro-opiomelanocortin molecule.

Adolescent↗
PubMed1999

Tissue inhibitor of metalloproteinase-2 (TIMP-2) expression is strongly induced by ACTH in adrenocortical cells.

Besides its acute and chronic effects on corticosteroid synthesis, the pituitary adrenocorticotropic hormone (ACTH) regulates diverse adrenocortical biological functions including the synthesis of a number of mitochondrial, cytoplasmic, and secreted proteins. ACTH-induced secreted proteins are candidates to act as local extracellular relays of the hormone in either an autocrine or a paracrine manner. In the present study, we report that stimulation of primary cultures of bovine adrenocortical (BAC) fasciculata cells with 10 nM ACTH for 24 h results in a mean 8 +/- 4-fold induction of the synthesis of a secreted protein presenting an apparent Mr of 21 kDa. Peptide microsequencing and Western blotting allowed us to identify this 21-kDa ACTH-induced protein as the tissue inhibitor of metalloproteinase-2 (TIMP-2). The induction of TIMP-2 by ACTH required transcription, was mimicked by 8-bromo cyclic 3'-5' adenosine monophosphate, but was not observed in response to angiotensin II, IGF-1, fibroblast growth factor-2, transforming growth factor-beta1, or cortisol treatments. ACTH stimulated TIMP-2 mRNA levels by a factor 4, whereas TIMP-1 mRNA levels were not affected and TIMP-3 mRNA remained undetectable. The biological activity of TIMP-2 varied accordingly, as we observed that the conditioned medium of ACTH-treated BAC cells was four times more potent at inhibiting gelatinolytic activity than was the conditioned medium of control cells. Because the proteolytic activity of both progelatinase-B and progelatinase-A secreted by BAC cells remained latent, whether in the presence or in the absence of ACTH, a paracrine rather than autocrine role is proposed for TIMP-2 in the adrenal cortex.

Adrenal Cortex↗
PubMed1976

A comparative morphometric analysis of the effects of thyroxine and ACTH on the zona fasciculata of rat adrenal cortex.

The effects of thyroxine and ACTH on the ultrastructure of cells of the adrenal zona fasciculata were studied by morphometric analysis and compared by two-way analysis of variance. The results indicate that the effects of thyroxine and ACTH are different and independent. The statistically significant differences in effect of thyroxine and ACTH are: thyroxine causes an increase in the volume fraction of mitochondria and a decrease in the volume fraction of endoplasmic reticulum independent of ACTH; thyroxine causes a decrease in surface density of mitochondria and endoplasmic reticulum in the absence of ACTH, but in the presence of ACTH this effect is moderated by an interaction of throxine and ACTH. There were no statistically significant effects of either thyroxine or ACTH on volume fraction or surface density of liposomes.

Adrenal Cortex↗
PubMed1986

Effects of ACTH on seizure susceptibility in the developing brain.

Adrenocorticotropic hormone (ACTH) has been frequently used as an anticonvulsant drug in some childhood seizure disorders. Despite its widespread use, few studies have evaluated the effects of ACTH on seizure susceptibility in the developing animal or the long-term consequences of ACTH treatment on brain development. In this study, ACTH was given either for 2 days or 14 days prior to kindling in 15-, 22-, and 30-day-old rats. Morphological changes in the brain were studied using routine light microscopy and dendrite branch counting following Golgi staining. Both acute and chronic ACTH treatment inhibited the rate of kindling in all three age groups. There were no differences in brain morphology between the controls and the ACTH-treated rats killed shortly after kindling. Rats treated with ACTH and killed as adults, however, had significantly more dendrite branches than did controls. In the immature brain, ACTH treatment reduces seizure susceptibility and has no long-term deleterious effects on neuronal growth.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Plasma cortisol following injection of 1-39 or 1-18 ACTH.

Forty units of 1-39 ACTH of animal origin or 0.4 mg of synthetic 1-18 ACTH administered at 8 A.M. via either the intramuscular route to 10 subjects with intact adrenocortical function produced comparable increases in plasma cortisol at 1, 2, and 6 hours. The increase in plasma cortisol lasted at least 6 hours but less than 12 hours after intravenous crystalline 1-39 ACTH and at least 16 hours but less than 24 hours after the same dose of 1-39 ACTH administered as a depot gel via the intramuscular route. However, neither intravenous nor the intramuscular injection of 1-39 ACTH produced increases that were still evident at 24 hours. Following either the intramuscular or intravenous injection of 0.4 mg of the synthetic 1-18 ACTH, the plasma cortisol increase was still evident at the 24th hour. Our findings indicate that the plasma cortisol responses to either 40 units of exogenous 1-39 ACTH of animal origin or to 0.4 mg of a synthetic 1-18 ACTH are most consistent in the first 6 hours following either intravenous or intramuscular injection.

Adrenocorticotropic Hormone↗
PubMed2004

Release of aldosterone and catecholamines from the interrenal gland of Triturus carnifex in response to adrenocorticotropic hormone (ACTH) administration.

The influence of adrenocorticotropic hormone (ACTH) on the interrenal gland of Triturus carnifex was investigated by in vivo administration of synthetic ACTH. The effects were evaluated by examination of the ultrastructural morphological and morphometrical features of the tissues as well as the circulating serum levels of aldosterone, noradrenaline (NA), and adrenaline (A). In June and November, ACTH administration increased aldosterone release (from 281.50 +/- 1.60 pg/ml in carrier-injected newts to 597.02 +/- 3.35 pg/ml in June; from 187.45 +/- 1.34 pg/ml in carrier-injected animals to 651.00 +/- 3.61 pg/ml in November). The steroidogenic cells showed clear signs of stimulation, together with a reduction of lipid content in June and an increase of lipid content in November. Moreover, ACTH administration decreased the mean total number of secretory vesicles in the chromaffin cells in June (from 7.73 +/- 0.60 granules/microm2 in carrier-injected animals to 5.91 +/- 0.40 granules/microm2) and November (from 7.78 +/- 0.75 granules/microm2 in carrier-injected newts to 4.87 +/- 0.40 granules/microm2). In June, however, when T. carnifex chromaffin cells contain almost exclusively NA granules (NA: 7.42 +/- 0.86 granules/microm2; A: 0.32 +/- 0.13 granules/microm2), ACTH decreased NA content (5.52 +/- 0.32 granules/microm2) increasing NA release (from 639.82 +/- 3.30 pg/ml in carrier-injected to 880.55 +/- 4.52 pg/ml). In November, when both catecholamines, NA (3.92 +/- 0.34 granules/microm2) and A (3.84 +/- 0.33 granules/microm2), are present in the chromaffin cells, ACTH administration reduced A content (1.02 +/- 0.20 granules/microm2), enhancing adrenaline secretion (from 681.30 +/- 3.62 pg/ml in carrier-injected newts to 1,335.73 +/- 9.03 pg/ml). The results of this study indicate that ACTH influences the steroidogenic tissue, eliciting aldosterone release. The effects on the chromaffin tissue, increase of NA or A secretion, according to the period of chromaffin cell functional cycle, may be direct and/or mediated through the increase of aldosterone release. Finally, the lack of an increase of A content in the chromaffin cells, or A serum level, following ACTH administration in June might suggest an independence of PNMT enzyme on corticosteroids.

Adrenocorticotropic Hormone↗
PubMed1993

The biologic activity of ACTH and related peptides on peripheral blood mononuclear cells is altered by the presence of dexamethasone.

We wished to determine whether the glucocorticoid hormone dexamethasone (dex), a potent modular of both pituitary-adrenal and immunologic activity, altered the effect of adrenocorticotropin-related peptides on activated peripheral blood mononuclear cells (PBMCs) and T-cells. PBMCs preactivated with Concanavalin A (Con A) and T-cells preactivated with phorbol 12,13 dibutyrate (PDB) plus phytohemagglutinin (PHA) were exposed to dex, ACTH, and related peptide sequences. Proliferation of cells was measured as was IL-2 in conditioned media. It was found that in the absence of dex only the peptide ACTH(18-39) altered proliferation of PBMCs while there was no effect of peptide on T-cells activated via protein kinase C-mediated pathways. Significant reversal of the inhibitory effect of dex on proliferation of PBMCs exposed to Con A was achieved with addition of ACTH(1-39) and ACTH(11-24), while IL-2 levels were unaffected by the addition of peptide. ACTH(18-39) and ACTH(11-24) enhanced the inhibitory effect of dex on T-cells activated with PDB plus PHA. These findings suggest that the biologic activity of ACTH on immune cells is altered when dexamethasone is present and under certain circumstances ACTH may protect the immunologic response from the inhibitory effects of elevated ambient glucocorticoids.

Adrenocorticotropic Hormone↗
PubMed1998

Characteristics of the proopiomelanocortin system in the outdoor-bred domestic gander. I. ACTH and beta-endorphin levels in the brain, pituitary, and plasma.

Immunoreactive (ir-) adrenocorticotropic hormone (ACTH) and beta-endorphin (beta E) levels were determined in seven brain regions, in the three pituitary lobes, and in the plasma of the domestic gander by specific radioimmunoassays. In the brain regions studied the relative concentrations of ir-ACTH and ir-beta E were the highest in the mediobasal hypothalamus and in the paraventricular nucleus. There were lower levels of these peptides in the supraoptic nucleus, in the septum, and in the dorsal thalamus. Very low ir-ACTH and -beta E contents were found in the archistriatum and in the lobus parolfactorius. In the pars distalis of the pituitary gland the cephalic lobe contained about 10 times more ir-ACTH (3596 pmol/lobe) and 4 times more ir-beta E (867 pmol/ lobe) than the caudal lobe (383 pmol/lobe and 189 pmol/lobe, respectively). Sephadex G-50 chromatography of pooled cephalic and caudal lobe extracts resulted in two distinct ir-beta E peaks, with elution volumes corresponding to the mammalian beta-lipotropin and beta E, and three ir-ACTH peaks, the second one coeluting with mammalian ACTH. In the neural lobe the ir-ACTH/-beta E concentrations were similar to those in the hypothalamus. Resting plasma ir-ACTH (12.8 +/- 1.47 pmol/ml) but not ir-beta E (31.4 +/- 1.22 pmol/ml) levels were significantly increased following castration (to 41.4 +/- 1.11 pmol/ml). Serial blood sampling indicated pulsatile ir-beta E secretion (mean, coefficients of variation, and minimum-maximum range: 17.5, 62.78, and 2.9-49.7, respectively, for gander 1 and 23.3, 62.85, and 5.00-61.5, respectively, for gander 2).

Adrenocorticotropic Hormone↗
PubMed1988

Molecular transduction mechanisms in ACTH-induced grooming.

Intraventricular administration of ACTH1-24 induces excessive grooming in the rat. Ethogram analysis shows that the peptide does not alter grooming behavior seen in a novel box, but that it prolongs the duration of the grooming bout. Extensive structure-activity studies have been performed which suggest that the active site lies in a region (5-13) of the ACTH molecule. Interestingly, the (1-24) sequence is fully active, whereas (1-10) and (11-24) alone or in combination are inactive, pointing to a specific stereoconformation necessary to induce grooming. However, despite the fact that there are ACTH-and/or alpha-MSH-containing peptidergic neurons, no conclusive evidence is available demonstrating stereospecific, saturable binding sites for these peptides in brain. The analysis of the neural substrate underlying ACTH-induced excessive grooming has been performed by means of electrolytic lesions of specific brain regions and by neuropharmacological manipulations. The data suggest that the periaqueductal gray is the primary target for ACTH and that the activity of neostriatum and accumbens, via a nigro-colliculus-periaqueductal gray pathway, modulates the display of excessive grooming. An important feature of the neural substrate is that it displays single-dose tolerance to the peptide during the first hours after the first peptide injection. It is suggested that the tolerance is a feature of an opioid receptor-containing component of the neural substrate. The molecular mechanism of action of ACTH is complex and may involve different transmembrane signal transduction systems. The peptide decreases the degree of phosphorylation of a neuron-specific, synaptic phosphoprotein B-50 by inhibition of protein kinase C. It is concluded that changes in the degree of phosphorylation of B-50 regulate the activity of the lipid kinase phosphatidylinositol 4-phosphate kinase. Therefore, the B-50 protein seems to be part of a negative feedback loop in the receptor-activated hydrolysis of phosphatidylinositol 4,5-bis-phosphate (PIP2). There is increasing evidence that the molecular mechanism by which ACTH brings about the grooming response involves a change in phosphorylation of B-50. Firstly, the structure-activity relationship of ACTH-induced excessive grooming is nearly identical to that obtained for ACTH-induced inhibition of protein kinase C.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

Adenosine regulates the release of adrenocorticotropic hormone (ACTH) from cultured anterior pituitary cells.

We have recently shown the presence of adenosine receptors coupled to adenylate cyclase in anterior pituitary and in the present studies we have investigated the effects of adenosine on ACTH release. The 'R'-site specific analogs of adenosine such as N-Ethylcarboxamide adenosine (NECA), L-N6-phenylisopropyl adenosine (PIA), 2-chloro-adenosine (2-Cl-Ado) all stimulated ACTH release in a dose-dependent manner. NECA was the most potent analog and stimulated ACTH release by about 170% with an apparent Ka of 0.1 microM, whereas PIA and 2-Cl-Ado were less potent and stimulated the release by about 110% and 125% with an apparent Ka of 0.2 and 0.4 microM respectively. The stimulation of ACTH release by NECA was inhibited by 3-isobutyl-1-methylxanthine (IBMX). On the other hand, adenosine deaminase (ADA) treatment of the cells also stimulated ACTH release as well as adenylate cyclase activity by about 2-fold, suggesting that endogenous adenosine plays an inhibitory role in the release of ACTH. Other agents, such as corticotropin-releasing factor (CRF), vasoactive intestinal peptide (VIP) and forskolin (FSK) also stimulated ACTH release from these cells. In addition, the stimulation by an optimal concentration of NECA was almost additive with maximal stimulation caused by VIP and FSK. These data suggest that adenosine modulates ACTH release from anterior pituitary through its interaction with adenosine receptors coupled to adenylate cyclase.

Adenosine↗
PubMed1986

Differential subcellular localization of ACTH and alpha-MSH in corticotropes of the rat anterior pituitary.

Specific antisera to alpha-melanotropin (alpha-MSH) and corticotropin (ACTH 1-39) were used to obtain immunocytochemical evidence for the differential localization of alpha-MSH and ACTH in the secretory granules of corticotropes of rat anterior pituitary. The specificity of the antisera was established by binding 131I-labeled alpha-MSH and ACTH 1-39 to their respective antisera. Double-labeling immunocytochemistry (for alpha-MSH, ferritin; for ACTH, colloidal gold) was performed. Some secretory granules were labeled with ferritin particles (alpha-MSH), whereas others contained gold particles (ACTH). Only a few granules showed both ACTH and alpha-MSH. In typical corticotropes (stellate in form with a small number of secretory granules aligned along the cell periphery) only some of the secretory granules that were labeled with anti-ACTH serum were also immunoreactive to anti-alpha-MSH. In atypical corticotropes (polygonal in shape and containing a large number of secretory granules) almost all of the immunoreactive ACTH secretory granules were also positive to anti-alpha-MSH serum. An intermediate type of corticotrope was observed containing a small number of secretory granules, almost all of which were labeled with anti-alpha-MSH. Thus, rat anterior pituitary corticotropes may be classified into three types according to the distribution and content of alpha-MSH. The light-microscopic immunocytochemistry provided similar results.

Adrenocorticotropic Hormone↗