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PubMedDate not supplied

Localization of multiple forms of ACTH- and beta-endorphin-related substances in the pituitary of the reptile, Anolis carolinensis.

Immunohistochemical studies on the pituitary of Anolis carolinensis detected ACTH-like, beta-endorphin-like, and 16K fragment-like immunoreactivity in distinct clusters of cells in the anterior lobe; ACTH-like, alpha MSH-like, beta-endorphin-like, and 16K fragment-like immunoreactivity was detected in all the cells of the intermediate lobe. Crude acid extracts of both lobes, when analyzed by radioimmunoassay, gave displacement curves in ACTH and beta-endorphin assays which were parallel to the appropriate synthetic standard. Only extracts of the intermediate lobe gave parallel displacement curves in an alpha MSH radioimmunoassay. Extracts of both lobes crossreacted with antiserum to 16K fragment, but the displacement curves were not parallel to that of mouse 16K fragment standard. The levels of immunoreactive ACTH and beta-endorphin in the intermediate lobe were approximately 8-fold higher than in the anterior lobe. Fractionation of anterior lobe and intermediate lobe extracts by either gel filtration on Sephadex G-75 in 10% formic acid or sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed multiple forms of ACTH-related and beta-endorphin-related substances in both lobes. In the anterior lobe the major forms of immunoreactivity were, respectively, ACTH-sized and beta-endorphin-sized. In the intermediate lobe the major forms of immunoreactivity were alpha MSH-sized, CLIP-sized, and beta-endorphin-sized. In both lobes, antisera directed against ACTH and beta-endorphin detected high molecular weight material with an apparent molecular weight slightly less than that of mouse pro-ACTH/endorphin; this material probably represents the putative common precursor for ACTH and beta-endorphin in this species.

Adrenocorticotropic Hormone↗
PubMedDate not supplied

The role of calcium in the mechanism of corticotropin releasing factor mediated ACTH release.

To investigate the role of calcium (Ca+2) in CRF stimulated ACTH release, we studied the effect of the following conditions on CRF (10 nM) mediated ACTH release in primary pituitary monolayer culture: different concentrations of Ca+2; EGTA; lanthanum (La+3) and nifedipine, blockers of calcium cell influx and penfluridol, trifluoperazine, and pimozide, inhibitors of calmodulin activation. Higher concentrations of Ca+2 in the culture medium led to greater amounts of CRF induced ACTH release. EGTA at 3 mM decreased the amount of CRF stimulated ACTH release by 60% but did not alter the spontaneous release of ACTH. At 0.5 mM and 1.0 mM La+3, ACTH release induced by CRF was inhibited by 23% and 35% respectively (p less than 0.01). Nifedipine (both 10(-5) and 10(-4) M) inhibited CRF stimulated ACTH release but only to a maximum of 30%. This inhibition was completely overcome by the addition of 12 mM calcium. Penfluridol, pimozide, and trifluoperazine blocked the release of ACTH induced by CRF by 63%, 26%, and 0% respectively. In conclusion, extracellular Ca+2, Ca+2 influx, and calmodulin play a role in the mechanism of CRF stimulated ACTH in vitro.

Adrenocorticotropic Hormone↗
PubMed1984

The hemodynamic effects of prostacyclin infusions in normotensive and ACTH induced hypertensive conscious sheep.

The aim of this study was to determine the effect of ACTH-induced hypertension on the hemodynamic dose-response curves to intravenous infusion of prostacyclin (PGI2) in conscious sheep. PGI2 was infused for 10 minutes at doses of 0.05-0.50 micrograms/kg per min and hemodynamic dose-response curves were performed before, during and after ACTH-induced hypertension. Prior to ACTH administration prostacyclin infusions produced dose dependent decreases in mean arterial pressure (MAP), calculated total peripheral resistance (CTPR) and stroke volume (SV). These changes were accompanied by an increase in cardiac rate (CR) and cardiac output (CO). After five days of ACTH treatment MAP had risen from 72 +/- 1 to 91 +/- 2 mm Hg and infusions of PGI2 produced similar effects on MAP to those seen prior to ACTH. However the effects on CTPR, CO, SV and CR were all potentiated relative to normotensive animals. Three days after ACTH administration had ceased and basal pressure had returned to normotensive levels, the responses of CR, CO and SV to PGI2 infusions were similar to those seen prior to ACTH. However the exaggerated fall in CTPR seen during ACTH treatment was still present and this resulted in a very large decrease in MAP. These studies suggest that in this model of steroid-induced hypertension the resistance vessels are more sensitive to PGI2 and that the blood pressure response to PGI2 is regulated by different mechanisms to those seen prior to ACTH.

Adrenocorticotropic Hormone↗
PubMed1988

Relationship of increased food intake and plasma ACTH levels to 5-HT1A receptor activation in rats.

Various putative agonists of the 5-HT1A receptor subtype induce feeding in rats, probably by activating raphé somatodendritic 5-HT autoreceptors. These drugs also produce a marked increase in plasma concentrations of corticotropin (ACTH). In the present experiment we attempted to localize the site of action of 5-HT1A agonists on the secretion of ACTH and examined the relationship between 5-HT1A agonist-induced feeding and ACTH secretion. Rats were injected with either the high affinity 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (0.016-1.0 mg/kg, s.c.) or the novel anxiolytics buspirone, gepirone or ipsapirone (2.0-16.0 mg/kg, s.c.), and either had their food intake measured 2 hr post injection or were sacrificed 30-40 min post injection for measurement of plasma ACTH. Plasma ACTH also was measured in rats pretreated with the serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) for three days (150 mg/kg, i.p. per day) and subsequently injected with 8-OH-DPAT (0.3 mg/kg, s.c.). As previously reported, the 5-HT1A agonists increased both food agonists increased both food intake and plasma ACTH concentrations. After 8-OH-DPAT, ipsapirone and gepirone the amount of food consumed was positively correlated with the concentration of plasma ACTH. No such correlation was evident following buspirone. PCPA pretreatment resulted in near total depletion of brain 5-HT content but had no effect on the ACTH rise induced by 8-OH-DPAT. Therefore, in contrast to the presynaptic site previously proposed for 5-HT1A agonist-induced feeding, the present results suggest a agonist-induced feeding, the present results suggest a postsynaptic location for the 5-HT1A receptor mediating ACTH release.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Differential effects of prenatal and postnatal ACTH or nicotine exposure on 5-HT high affinity uptake in the neonatal rat brain.

These studies were designed to examine the differential effects of prenatal or postnatal administration of ACTH 1-39 and nicotine, on 5-HT high affinity uptake in brainstem and hippocampal synaptosomes. ACTH was administered prenatally (to pregnant dams) and postnatally to the neonates. Postnatal administration of ACTH significantly increased high-affinity 5-HT uptake in the hippocampus and especially the brainstem at both 7 and 21 days after birth. Prenatal ACTH, on the other hand, transiently increased 5-HT uptake in only the brainstem at 7 days, a change that was reversed at 21 days. While the effects of postnatal nicotine administration were essentially the same as those of postnatal ACTH treatment, prenatal nicotine, unlike ACTH, did not alter 5-HT uptake in 7-day-old rats but did reduce uptake in both tissues at 21 days. The observation that postnatal nicotine mimics the effects of postnatal ACTH and that nicotine stimulates ACTH release, suggests that the postnatal effects of nicotine may be exerted through ACTH.

Adrenocorticotropic Hormone↗
PubMed1989

Cortisol-induced inhibition of ACTH secretion in adult sheep.

Previous results from this laboratory have demonstrated that in preterm fetal sheep (117-131 days gestation), stimulated ACTH secretion is highly sensitive and that in term fetal sheep (129-143 days), stimulated ACTH secretion is insensitive to the negative feedback effects of cortisol. The purpose of this study was to quantitate cortisol negative feedback inhibition of stimulated ACTH secretion in adult sheep. Adult, conscious, nonpregnant ewes, chronically prepared with carotid arterial loops, were infused intravenously with vehicle or cortisol at 4 different rates (denoted Groups I, II, III, and IV) for 5 hours. These infusions increased total and unbound plasma cortisol concentrations within the range observed after stimulation of the hypothalamus-pituitary-adrenal axis. One hour after termination of the cortisol or vehicle infusions, ACTH secretion was stimulated by intravenous infusion of sodium nitroprusside for 10 min at a rate of 20 micrograms/kg.min. Cortisol infusions suppressed ACTH responses to nitroprusside in a dose-related manner. After vehicle infusion, nitroprusside increased plasma ACTH to 735 +/- 229 pg/ml. After cortisol infusions, nitroprusside increased plasma ACTH to 292 +/- 63, 101 +/- 30, 73 +/- 12, and 67 +/- 24 in Groups I, II, III, and IV, respectively. Overall, there was a significant negative exponential relationship between plateau plasma cortisol concentration during the cortisol or vehicle infusion and the peak plasma ACTH concentration during the response to nitroprusside infusion (r = -0.81). The highest rate of cortisol infusion increased total and unbound plasma cortisol concentrations to 40.1 +/- 5.7 and 19.5 +/- 5.9 ng/ml and completely suppressed the subsequent ACTH response to nitroprusside.

Adrenocorticotropic Hormone↗
PubMed1991

Effects of insulin-like growth factor I (IGF-I) on enzymatic activity in human adrenocortical cells. Interactions with ACTH.

Cells obtained from 6 adult human adrenals or adrenal fragments were cultured in serum-free synthetic medium (McCoy's) in order to study the isolated effects of IGF-I on steroidogenesis and its interactions with ACTH. After addition of peptide, changes in the activities of steroidogenic enzymes were assessed by measuring certain steroids in the spent medium. These included pregnenolone, 17-hydroxypregnenolone (17-OH-Preg), dehydroepiandrosterone (DHA), 17-hydroxyprogesterone (17-OH-P), androstenedione (AD), 11-deoxycortisol and glucocorticoids (chiefly cortisol and its immediate precursors, 11-deoxycortisol and 17-OH-P) and cortisol itself. The steroid responses obtained with repeated doses of IGF-I (40 ng/ml approximately 10(-9) M), added at 0, 48 and 72 h, over 4 days' culture were quite different from those obtained with repeated doses of ACTH (0.25 ng/ml approximately 10(-10) M). All the steroids measured increased with time of culture under the influence of ACTH and, apart from pregnenolone which peaked, tended to reach a plateau. With IGF-I, by contrast, DHA, AD, 11-deoxycortisol and glucocorticoid production increased initially, then decreased progressively, whereas pregnenolone, 17-OH-Preg and 17-OH-P production was either absent or negative. Cumulative steroid production over 4 days reached similar levels in response to a single dose of IGF-I and/or ACTH, with two major exceptions: pregnenolone dropped significantly with IGF-I [46% +/- 6 (SEM) as opposed to 93% +/- 11 with ACTH, P less than 0.005, n = 5], as did 17-OH-P (48% +/- 11 vs 113% +/- 8 with ACTH, P less than 0.001, n = 6). Increased formation of down-stream metabolites (DHA, AD, 11-deoxycortisol and glucocorticoids) would suggest that IGF-I induced stimulation of the 17 alpha-, 21- and 11 beta-hydroxylases. The responses to ACTH stimulation of cells which 4 days previously had been pre-treated with an initial and single dose of IGF-I and/or ACTH emphasized the impact of IGF-I on the 3-hydroxylation steps in cortisol biosynthesis. Compared with ACTH pre-treatment, the effects of which faded in the long term, pre-treatment with IGF-I resulted in a significantly increased steroidogenic response (P between less than 0.05 and less than 0.01). With the single exception of pregnenolone (43% +/- 4.7), production of all the metabolites was amplified: 17-OH-Preg: 348% +/- 88; DHA: 643% +/- 127; 17-OH-P: 193% +/- 36; AD: 725% +/- 200; 11-deoxycortisol: 573% +/- 110; cortisol: 1000%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗
PubMed1983

Action of peptidases in brain synaptic membranes on the NH2-terminus of adrenocorticotropin using ACTH-(1-16)-NH2 as a model substrate.

The action of brain peptidases on NH2-terminal sequences of adrenocorticotropin was studied by incubation of ACTH-(1-16)-NH2 under different pH conditions. Profiles of metabolites and time course of product formation were obtained by HPLC analysis of the digests. Fragments of ACTH-(1-16)-NH2 were isolated and characterized by their amino acid composition and NH2-terminal groups. Both at pH 7.4 and pH 8.5 the following fragments were found: ACTH-(3-16)-NH2, ACTH-(4-16)-NH2, ACTH-(5-16)-NH2, and ACTH-(7-16)-NH2. At pH 7.4 the major products were ACTH-(4-16)-NH2 and ACTH-(7-16)-NH2, while the peptide ACTH-(3-16)-NH2 was the main metabolite at pH 8.5. The nature of identified peptides and the time course of their formation demonstrates that aminopeptidase activities predominate in the conversion of the NH2-terminus of adreno-corticotropin and related peptides by brain synaptic membranes.

Adrenocorticotropic Hormone↗
PubMed2002

Loss of ACTH expression in cultured human corticotroph macroadenoma cells is consistent with loss of the POMC gene signal sequence.

The proopiomelanocortin (POMC) gene is highly expressed in the pituitary gland where the resulting mRNA of 1200 base pairs (bp) gives rise to a full-length protein sequence. In peripheral tissues however both shorter and longer POMC variants have been described, these include for example placental tissue which contain 800 (truncated at the 5' end) and 1500 as well as the 1200 bp transcripts. The importance of the 800 bp transcript is unclear as the lack of a signal sequence renders the molecule to be non-functional. This transcript has not been previously demonstrated in the pituitary gland. In this report we show evidence of a 5' truncated POMC gene in human pituitary corticotroph macroadenoma cells (JE) maintained in primary culture for >1 year. The original tumour tissue and the derived cells during early passage (up to passage 4-5) immunostained for ACTH and in situ hybridisation confirmed the presence of the POMC gene in the cultured cells. These cells also secreted 15-40 pg/10(5) cells/24 h ACTH. In addition, as expected RT-PCR demonstrated the presence of all three POMC gene exons and is thus indicative of a full-length POMC gene. In late culture passages (passages 8-15) JE cells ceased to express ACTH and cell growth became very slow due presumably to cells reaching their Hayflick limit. ACTH immunostaining in these cells was undetectable and ACTH secretion was also at the detection limits of the assay and no greater than 10 pg/10(5) cells/24 h. ACTH precursor molecules were also undetectable. RT-PCR for the POMC gene in these late passage cells showed that only exon 3 was detectable, in contrast to early passage cells where all three exons were present. In summary we isolated in culture, human pituitary cells that possessed initially all three exons of the POMC gene and immunostained for ACTH. On further passaging these cells showed a loss of exons 1 and 2 in the POMC gene and a loss of ACTH immunostaining and secretion. We would like to suggest that the loss of ACTH peptide expression in these late passage cells is in part due to the loss of the POMC signal sequence. An alternative explanation for our findings is that there were originally two populations of corticotrophs in the cultures, one of which possessed the full-length POMC gene and the other only the 5' truncated POMC transcript and it is these latter cells which survived in culture. In either scenario this is the first report of the 5' truncated POMC gene occurring in pituitary cells.

Adenoma↗
PubMed2002

Intraoperative bilateral cavernous sinus sampling for ACTH measurements during transsphenoidal pituitary surgery in patients with Cushing's disease.

Intraoperative bilateral cavernous sinus sampling combined with rapid ACTH measurement was performed in a pilot study in seven patients with Cushing's disease during transsphenoidal pituitary surgery before and immediately after removal of the ACTH-producing pituitary microadenoma. Before tumor removal a gradient in ACTH concentrations greater than 1.5:1 toward the side of the tumor was found in six patients whereas ACTH concentrations in the right and left cavernous sinuses were similar in one patient with a midline tumor. Immediately after tumor removal, six of seven patients showed variable decreases in ACTH levels in the ipsilateral and/or contralateral side, whereas in one patient the ACTH levels in cavernous sinuses failed to reflect successful tumor removal. These results indicate that intraoperative bilateral cavernous sinus sampling combined with rapid ACTH measurement may be useful to confirm and lateralize ACTH-producing pituitary microadenomas during surgery, but ACTH levels measured immediately after tumor removal do not always predict surgical cure.

Adenoma↗
PubMed2000

Reduced adrenocortical responsiveness to adrenocorticotropic hormone (ACTH) in socially subordinate female marmoset monkeys.

Socially subordinate female common marmoset monkeys undergo pronounced, chronic reductions in basal plasma cortisol levels, which appear to result both from socially induced suppression of reproductive hormones and from direct effects of social subordination. In this study, we tested the hypothesis that this cortisol suppression is mediated by reduced adrenocortical responsiveness to adrenocorticotropic hormone (ACTH). Dominant, subordinate, and ovariectomized females were given dexamethasone (5 mg/kg, IM), followed the next morning by human ACTH(1-39) (10 microg/kg, IV) or sterile saline (0.5 ml/kg, IV); blood samples were collected at -20 through 150 min from ACTH or saline treatment and assayed for cortisol. ACTH, but not saline, caused a marked elevation of plasma cortisol levels. Prior to ACTH treatment, dominant females tended to have higher dexamethasone-suppressed cortisol levels than subordinate and ovariectomized females. After ACTH treatment, dominant females had significantly higher cortisol concentrations, as well as higher peak and net integrated cortisol responses to ACTH, than did subordinate and ovariectomized animals; the latter two groups showed comparable cortisol responses to ACTH. These results suggest that dampened adrenocortical responsiveness to ACTH contributes to chronic reductions in cortisol levels in subordinate female marmosets and may be mediated by suppression of reproductive hormones.

Adrenal Cortex↗
PubMed2004

Social suppression of cortisol in female marmoset monkeys: role of circulating ACTH levels and glucocorticoid negative feedback.

Behaviorally subordinate female common marmoset monkeys (Callithrix jacchus) exhibit pronounced, chronic reductions of circulating cortisol levels. Cortisol suppression in these animals is mediated in part by adrenocortical hyporesponsiveness to adrenocorticotropic hormone (ACTH). In addition, we hypothesized that social subordination may activate a central, neurally mediated mechanism to further inhibit hypothalamo-pituitary-adrenal function. In this study, therefore, we evaluated basal plasma cortisol and ACTH concentrations, as well as cortisol and ACTH responses to dexamethasone (DEX), in dominant and subordinate females to initially characterize such a mechanism. Morning plasma cortisol and ACTH levels were determined before, and 1, 2, and 3 days following administration of DEX (0.5, 1.0, or 5.0 mg/kg, IM) or saline. Baseline cortisol concentrations prior to DEX treatment were significantly lower in subordinate females than in dominants, as previously reported. However, ACTH concentrations in the same blood samples did not differ between the two groups. Furthermore, dominant and subordinate females showed similar cortisol and ACTH responses to DEX. These results indicate that reduced circulating cortisol levels in subordinate females are not associated with either altered circulating ACTH concentrations or enhanced responsiveness to glucocorticoid negative feedback. However, the finding that basal ACTH levels are not elevated in subordinate females as compared to dominants, in spite of low circulating cortisol concentrations, suggests that ACTH secretion in subordinate females is restrained by a steroid-independent inhibitory mechanism operating at the level of the brain or pituitary.

Adaptation, Physiological↗
PubMed2001

Extremely low-dose ACTH therapy for West syndrome in Japan.

Adrenocorticotropic hormone (ACTH) therapy is a widely used and effective treatment for West syndrome. However, serious adverse effects can occur during or shortly after ACTH therapy. Synthetic ACTH has been reported to cause more adverse effects than natural ACTH. Currently, most Japanese pediatric neurologists try other non-hormonal treatments before using ACTH therapy, but even then, they use extremely low dosages of synthetic ACTH. The extremely low-dose synthetic ACTH therapy currently used in Japan is as effective for treatment of West syndrome as the higher doses reported in previous studies from Japan and Western countries. The dosage and duration of synthetic ACTH therapy should be as low as possible to avoid serious adverse effects. Close monitoring of the adverse effects, especially subdural hematoma, is necessary even when extremely low dosages of ACTH are administered.

Adrenocorticotropic Hormone↗
PubMed2002

ACTH promotion of p27(Kip1) induction in mouse Y1 adrenocortical tumor cells is dependent on both PKA activation and Akt/PKB inactivation.

Here we report antimitogenic mechanisms activated by the adrenocorticotropic hormone (ACTH) in the mouse Y1 adrenocortical tumor cell line. ACTH receptors activate the Galphas/adenylate cyclase cAMP/PKA pathway to promote dephosphorylation of Akt/PKB enzymes, leading to induction of the cyclin-dependent kinases' (CDKs) inhibitor p27(Kip1). Y1 cells display high constitutive levels of phosphorylated Akt/PKB dependent on chronically elevated c-Ki-Ras.GTP and PI3K activity. Expression of the dominant negative mutant RasN17 in Y1 cells results in strong reduction of both c-Ki-Ras.GTP and phosphorylated Akt/PKB, which are restored by FGF2 treatments. Inhibitors of PI3K lead to rapid dephosphorylation of Akt/PKB and block phosphorylation of Akt/PKB promoted by FGF2. ACTH rapidly promotes dephosphorylation of Akt/PKB in Y1 adrenal cells, while constitutively high levels of c-Ki-Ras.GTP remain unchanged. ACTH and cAMP elevating agents fail to cause Akt/PKB dephosphorylation in PKA-deficient clonal mutants of Y1 cells. In addition, cholera toxin, forskolin, and 8BrcAMP all mimic ACTH, causing dephosphorylation of Akt/PKB in wild-type Y1 cells. ACTH is unable to prevent Akt/PKB phosphorylation, promoted by FGF2 in clonal lines of RasN17-Y1 transfectants displaying negligible levels of c-Ki-Ras.GTP. ACTH promotes strong p27(Kip1) protein induction in wild-type Y1 adrenocortical cells but not in PKA-deficient Y1-clonal mutants nor in RasN17-Y1 transfectants. PI3K inhibitors induce p27(Kip1) protein in all cells studied, i.e., wild type and transfectants. The inverse correlation between levels of phosphorylated Akt/PKB and of p27(Kip1) protein caused by ACTH suggests a novel antimitogenic pathway activated by ACTH and mediated by cAMP/PKA in the mouse Y1 adrenocortical tumor cell line.

Adrenal Cortex Neoplasms↗
PubMed1977

Evidence for separate peptide sequences related to the lipolytic and magnesium-accumulating activities of ACTH. Analogy with adrenergic receptors.

Native adrenocorticotropin [ACTH-(1-39)] and ACTH-(1-24) stimulate both lipolysis and magnesium accumulation in rat adipocyte plasma membrane vesicles. ACTH-(1-20) retains full lipolytic activity but has a minimal effect on magnesium accumulation. In contrast ACTH-(11-24) stimulates magnesium accumulation but not lipolysis. These findings indicate that within the ACTH molecule the peptide sequence responsible for stimulation of magnesium accumulation is distinctly separate from the core sequence (residues 4-10) essential for stimulation of adenylyl cyclase activity and cAMP mediated lipolysis. Phentolamine, an alpha-adrenergic antagonist, blocks the bulk of magnesium accumulation stimulated by native ACTH and norepinephrine; propranolol, a beta-adrenergic antagonist, blocks the earliest phase of Mg2+ uptake by these hormones but has little effect on net uptake. Isoproterenol, a beta-adrenergic agonist, stimulates magnesium uptake only minimally. The pattern of uptake stimulated by methoxamine, an alpha-adrenergic agonist, or ACTH-(11-24) is quite similar to that produced by native ACTH in the presence of propranolol. The receptor through which ACTH mediates stimulation of the bulk of magnesium appears to be analogous to the alpha-adrenergic receptor through which norepinephrine stimulates this same process.

Adipose Tissue↗
PubMed1999

Reproducibility of the cortisol response to stimulation with the low dose (1 microg) of ACTH.

OBJECTIVE: Previous studies have shown that the rapid ACTH stimulation test using a low dose of 1 microg is more sensitive than that using 250 microg ACTH for detecting subtle cases of adrenal insufficiency. However, there are controversies for the reproducibility of the 1 microg-test. To evaluate the reproducibility of the 1 microg-test, we assessed both day-to-day and diurnal variations of cortisol responses to 1 microg ACTH injection. In addition, optimum sampling time for the 1 microg-test was also determined. SUBJECTS: AND DESIGN Eight healthy volunteers and five patients with secondary adrenal insufficiency were recruited. Healthy subjects were given 1 microg ACTH 3 times in the morning (0800 h) and 2 times in the afternoon (1600 h). Patients with adrenal insufficiency had 2-tests in the morning and 2 in the afternoon. Serum cortisol levels were measured every 10 minutes for 1 h after the injection. RESULTS: In healthy subjects, basal and peak serum cortisol levels were significantly higher in the morning (P < 0.05), whereas maximum cortisol increments were higher in the afternoon (P < 0.001). In patients with adrenal insufficiency, basal and peak serum cortisol levels in the morning were not different from corresponding values in the afternoon. Intra-individual coefficient of variation (CV) of peak serum cortisol response to 1 microg ACTH ranged from 3.0 to 16.4% in healthy subjects and 10.0-34. 4% in patients. Also, there was a significant correlation between peak morning or afternoon cortisol levels after 1 microg ACTH injection given in different days in both healthy subjects and patients. Twenty-six of the 40 studies in healthy subjects showed peak response at 20 minutes, while nine showed it at 30 minutes Using the data acquired at 20 and 30 minutes, all 40 studies in healthy subjects showed normal results while none of 20 studies in patients was normal. CONCLUSIONS: We conclude that the cortisol response to 1 microg ACTH stimulation was reproducible in both healthy subjects and patients with secondary adrenal insufficiency. In order to assess adrenal function more accurately with the 1 microg ACTH stimulation test, serum cortisol should be measured before and 20 and 30 minutes after ACTH injection.

Adrenal Cortex Diseases↗
PubMed2002

[Cushing's syndrome caused by paraneoplastic ACTH secretion 11 years after occurence of a medullary thyroid carcinoma].

HISTORY AND ADMISSION FINDINGS: A 47-year-old man, with known and treated hypertension for 2 years, was admitted because of recent marked weight gain. Eleven years before a medullary thyroid carcinoma had necessitated removal of his thyroid and parathyroids. He was not receiving levothyroxine, calcium and vitamin D. Physical examination revealed florid Cushing's syndrome with a "buffalo hump", plethora, truncal obesity and red striae. Both his mother and a maternal male cousin were reported to have had a medullary thyroid carcinoma. INVESTIGATIONS: Plasma ACTH was 80 pg/ml (normal 10-70 pg/ml), urinary cortisol 764 microgram/24 h (normal 20-100 microgram/24 h). ACTH rose to 93.1 pg/ml after dexamethasone, with little suppression of serum cortisol (reduced from 34.4 to 22.1 microgram/dl; normal 7-25 microgram/dl. Magnetic resonance imaging did not detected an abnormal hypophysis. Petrosal sinus catheterization revealed hypophyseal suppression of ACTH, without evidence of focal peripheral ACTH production. Calcitonin was 24 000 pg/ml (normal < 8.8 pg/ml). Computed tomography showed multiple round lesions in the liver (histology: metastasis of a C-cell carcinoma). Genetic test showed a multiple endocrine neoplasm type IIa. DIAGNOSIS, TREATMENT AND COURSE: The findings indicated Cushing's syndrome, most likely due to paraneoplastic ACTH secretion from a metastasis of the C-cell carcinoma. In the absence of a site of paraneoplastic ACTH secretion, bilateral adrenalectomy was performed. The plethora and striae regressed postoperatively and it was possible to reduce markedly the antihypertensive medication. CONCLUSION: An ectopic site of ACTH should be included in the differential diagnosis of Cushing's syndrome. This is the first reported case of a medullary thyroid carcinoma and ectopic ACTH production in which the paraneoplastic ACTH secretion had been delayed for 11 years.

Adrenalectomy↗
PubMed2003

[Investigations on regulation of CRH, ACTH and cortisol in trophoblast cells in vitro].

OBJECTIVE: Trophoblast cells synthesise CRH and ACTH, which are peptide hormones. On the strength of special enzymes they are capable of catalyzing the reaction cortisol <--> cortisone. In vitro experiments should give a proof of influence to ACTH- and cortisol secretion by CRH, ACTH and prednisolon. The basal rate of cortisol secretion was examined in a long term experiment. MATERIAL AND METHODS: Trophoblast cells were prepared from human term placentae by standard trypsin-DNAse dispersion of villous tissue followed by a percoll gradient centrifugation step. After adjusting the cell suspension to a defined cell concentration of 1 x 10(6) cells/ml the cells were cultivated. The addition of CRH, ACTH or prednisolon followed every eight hours. The samples collected 20 or 30 minutes later, also from unstimulated cultures, were assayed for ACTH and cortisol by enzyme-immunometric methods. RESULTS: The concentration of cortisol shows a rhythmical course in long term cell cultures. The addition of CRH (500 ng/ml, 1 microg/ml) stimulates the concentration of ACTH- and cortisol in a time-depending manner. The addition of ACTH (500 ng/ml-2 microg/ml) stimulates the concentration of cortisol in a time-depending manner. The addition of prednisolon stimulates the concentration of ACTH. CONCLUSIONS: The trophoblast cell shows a rhythmical course in the concentration of cortisol. For the first time a CRH-ACTH-cortisol feedback loop could be demonstrated in cultured trophoblast cells.

Adrenocorticotropic Hormone↗