And Corticotrophin Research Articles

DHEAS for the prediction of subclinical Cushing's syndrome: perplexing or advantageous?

The diagnostic accuracy of dehydroepiandrosterone sulfate (DHEAS) to predict subclinical Cushing's syndrome (sCS) has been a matter of debate. The primary objective of this study was to assess the diagnostic power of DHEAS in predicting sCS. This retrospective study was conducted in a tertiary referral center and based on subjects referred between 2004 and 2014. Data of 249 subjects with adrenal incidentalomas were evaluated. We also reviewed 604 DHEAS measurements from adults, which were performed during the same period in our laboratory (LB group). Adrenocortical function, tumor size, and clinical characteristics were assessed. We diagnosed sCS in 15.2 % of the participants in the presence of ≥2 of the following; 1 mg dexamethasone suppression test >3.0 μg/dl, urinary free cortisol >70 μg/24 h, and corticotrophin (ACTH) <10 pg/ml. DHEAS levels were significantly reduced in patients with sCS (n = 38) compared to sCS (-) (n = 141) and LB groups (n = 604) (27.95, 65.90, and 66.80 µg/dl, respectively, p < 0.001) while age was comparable. The ROC curve analysis showed that the cut-off of the DHEAS with the best diagnostic accuracy for detecting sCS was 40.0 μg/dl (SN, 68 %; SP, 75; PPV, 43 %; NPV, 90 %, AUC: 0.788, p < 0.001). Logistic regression assessed the impact of age, BMI, low DHEAS (<40 μg/dl), bilateral tumors, and tumor size on the likelihood of having sCS. The strongest predictor was low DHEAS, recording an OR of 9.41. DHEAS levels are inversely associated with the extent of cortisol excess. In subjects with intermediate laboratory findings, detection of low DHEAS could be advantageous for distinguishing sCS.

Effect of glucocorticoids pretreatment on steroidogenic capacity of adrenocortical cells isolated from Meishan piglets

The present in vitro experiment was designed to test whether 48h of pretreatment with glucocorticoids, cortisol, or dexamethasone (DEX), would affect basal and corticotrophin (ACTH) stimulated (24h) cortisol secretion from primary cultures of pig adrenocortical cells. Cells were divided into six groups: control pretreatment with or without ACTH challenge, cortisol pretreatment with or without ACTH challenge, and DEX pretreatment with or without ACTH. The culture medium and cells were collected at the end of treatment. Cortisol concentration in medium was measured by radioimmunoassay, and protein content of glucocorticoid receptor (GR) and key regulatory factors for steroidogenesis, including melanocortin type 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage cytochrome P450 (P450scc), were detected by Western blot analysis. The results showed that glucocorticoid pretreatment did not affect cortisol secretion under basal condition without ACTH challenge, but significantly enhanced ACTH-stimulated cortisol secretion. Furthermore, the protein content of GR, MC2R, StAR, and P450scc was all increased in groups pretreated with glucocorticoids. These results indicate that adrenocortical cells pretreated with glucocorticoids display higher steroidogenic capacity under ACTH challenge, through the upregulation of GR and other steroidogenic regulatory factors.

Presentation of ICAM-1 Protein at the Cell Surface of Oral Keratinocytes in the Presence of Adrenomedullin and Corticotrophin

Increasing evidence suggests that adrenomedullin (AM) and corticotrophin (ACTH) are immunomodulatory. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes not only from peripheral blood into inflamed tissues but also into epithelia. We have investigated the effects of AM and ACTH on the expression of ICAM-1 by human oral keratinocytes. The human oral keratinocyte cell line H357 was incubated with either AM or ACTH for up to 8 hrs and ICAM-1 expression was measured by cell surface ELISA. ICAM-1 was up regulated by both peptides and this was attenuated by the adenylyl cyclase inhibitor SQ22,536 and the NF-κB inhibitor SN-50. H357 cells constitutively express ICAM-1 mRNA and expression of this gene was significantly modulated by AM and ACTH. Furthermore AM caused translocation of NF-κB from the cytoplasm to the nucleus. This is the first report describing up regulation of ICAM-1 in oral keratinocytes by AM and ACTH and the results suggest both cAMP and NF-κB may play a role. These results further suggest both peptides may have an immunostimulatory role in oral muocsa and skin.

Stimulation of adhesion molecule expression in human endothelial cells (HUVEC) by adrenomedullin and corticotrophin.

Adrenomedullin (AM) and corticotrophin (ACTH) are both vasoactive peptides produced by a variety of cell types, including endothelial cells. Although AM and ACTH are considered to be important in the control of blood pressure and the response to stress, respectively, their role in inflammation and the immune response has not been clarified. This study shows, with the use of a cell-based ELISA, that AM and ACTH induce cell surface expression of the adhesion molecules E-selectin, VCAM-1, and ICAM-1 on human umbilical vein endothelial cells (HUVEC). Furthermore, this effect appears to be mediated in part via elevation of cAMP, given that both peptides elevate cAMP, the cell-permeable cAMP analog dibutyryl cAMP is able to mimic induction of all three cell adhesion molecules and the effect of AM and ACTH is inhibited by the adenylyl cyclase inhibitor SQ-22536. These findings demonstrate a role for AM and ACTH in the regulation of the immune and inflammatory response.

Associations between pituitary-adrenocortical function and abdominal obesity, hyperinsulinaemia and dyslipidaemia in normotensive males.

To examine the relationships between pituitary-adrenal cortical (PA) function, abdominal obesity, hyperinsulinaemia, and dyslipidaemia. A prospective study. Helsinki University Central Hospital, Finland. Seventy-one healthy males aged 30-55 years. Insulin sensitivity was assessed by the oral glucose tolerance test (OGTT). Basal PA activity was examined by measuring urinary and serum concentrations of hormones, followed by dexamethasone suppression and corticotrophin (ACTH) stimulation tests to determine functional PA activity. The means of waist-to-hip ratio (WHR), body-mass index (BMI), HDL-cholesterol and triglyceride levels, and insulin and C-peptide measurements during the OGTT were significantly different across the tertiles for insulin:glucose ratio. The ratio of 12-h urinary cortisol excretion to BMI, preceding the OGTT, and the mean basal cortisol level during the OGTT were decreased, while the net increments of cortisol and 17-hydroxyprogesterone (17-OHP) from 0 to 60 min, as well as the ratio of net 17-OHP to 11-deoxycortisol increments, after ACTH, were elevated in the upper compared with the lower tertile. The mean cortisol during the OGTT, and the ratio of urinary cortisol to BMI were negatively related, while absolute DHEA and cortisol responses to ACTH were positively related to fasting and mean insulin levels. Hormonal variables, WHR, insulin, and triglycerides were successfully integrated into a tentative mathematical model by the use of covariance structure (path) analyses. Several alterations in the PA function, suggestive of decreased 21-hydroxylase activity, mild cortisol deficiency and slight adrenal hyperplasia, are associated with abdominal obesity which, in turn, appears to be an important prelude to insulin resistance and dyslipidaemia.

5-HT1A Receptor Sensitivity in Major Depression

The hypothermic, growth hormone and corticotrophin (ACTH) responses to the 5-HT1A receptor agonist buspirone (30 mg orally) were measured in 20 unmedicated patients with major depression and 20 healthy controls. Compared with the controls, the hypothermic responses of the depressed patients to buspirone were significantly attenuated, particularly in patients with melancholic depression. In contrast, the responses of growth hormone and ACTH to buspirone were unchanged. The data suggest that major depression may be associated with impaired sensitivity of 5-HT1A autoreceptors but that the function of the post-synaptic 5-HT1A receptors that mediate growth hormone and ACTH release is unaltered. Within the limitations that attend the use of buspirone as a 5-HT1A probe, our data suggest that the decrement in serotonin neurotransmission at post-synaptic 5-HT1A receptors in depression is due to decreased serotonin release rather than impaired responsivity of post-synaptic 5-HT1A receptors.

Effects of chronic administration of melanin-concentrating hormone on corticotrophin, melanotrophin, and pigmentation in the trout

This paper reports the effects of salmonid melanin-concentrating hormone (MCH), administered via an Alzet minipump, on pigmentation and secretion of pituitary melanotrophin (MSH) and corticotrophin (ACTH) by black-adapted, adult rainbow trout. The drug induced melanin concentration in the skin melanophores and prevented melanogenesis. Both the cytological appearance of the pituitary pars intermedia and determinations of plasma α-MSH suggest that MCH prevented the increase in secretory activity of the melanotrophic cells seen normally in black-adapted trout. Resting plasma cortisol titres were similar in all groups of fish but anterior pituitary glands taken from stressed, MCH-treated fish released less ACTH in vitro than those from corresponding saline-treated fish.

Recovery of plasma corticotrophin and cortisol levels after three-week course of prednisolone.

Patients with chronic airflow obstruction were given a three-week course of prednisolone 40 mg per day. The basal plasma cortisol level and response to tetracosactrin were depressed after such a course. Basal plasma cortisol and corticotrophin (ACTH) levels were measured on five consecutive days after three weeks of treatment with prednisolone and were found to rise simultaneously to control levels within three days. Pituitary and adrenal functions were depressed for four days after short high dose courses of corticosteroids and patients may be at risk if they encounter stress during this time.

Effects of Acute and Chronic Administration of Narcotic Analgesics on Growth Hormone and Corticotrophin (ACTH) Secretion in Rats

Publisher Summary This chapter focuses on the experiments that are designed (1) to compare the acute effects of various narcotic analgesics on growth hormone (GH) and corticotrophin (ACTH)-secretion, and (2) to examine endocrine aspects of tolerance in rats treated chronically with morphine or methadone. The effects of narcotic analgesics on ACTH-secretion and on hypothalamo-pituitary systems have been reviewed recently. The effects of narcotic analgesics on GH and ACTH secretion in rats appear to be dose-related. The lower doses of morphine, methadone and codeine employed in this study mainly caused a rise of plasma GH and had little or no effect on plasma corticosterone. Higher doses of morphine and methadone produced increases of both plasma corticosterone and GH. Acute abstinence produced by naloxone resulted in a marked increase of plasma corticosterone and a diminution of plasma GH. Dose-response studies with narcotic antagonists showed that nalorphine produced simultaneous increases of plasma corticosterone and GH, while naloxone had no consistent effects on GH or ACTH secretion.

Additional evidence for dissociation of melanocyte-stimulating hormone and corticotrophin release.

During recent experiments in our laboratories it was noted that rats pharmacologically blocked with dexamethasone, morphine and sodium pentobarbitone showed increased plasma levels of melanocyte-stimulating hormone (MSH) and suppressed plasma levels of corticosterone. Since there exists increasing evidence that MSH has an extra-pigmentary function in mammals (DeWied, Bohus & Greven, 1968; Kastin, Kullander, Borglin, Dahlberg, Dyster-Aas, Krakau, Ingvar, Miller, Bowers & Schally, 1968; Kastin, Miller, Gonzalez-Barcena, Hawley, Dyster-Aas, Schally, DeParra & Velasco, 1971) and since there appears to be some discrepancy regarding the relationship of MSH and corticotrophin (ACTH) to various stimuli (Abe, Nicholson, Liddle, Orth & Island, 1969; Kastin, Schally, Viosca & Miller, 1969), it seemed appropriate to determine the effect of the pharmacological block — dexamethasone, morphine and sodium pentobarbitone — on the release of MSH and ACTH. Experiments were performed using adult (160–200 g) female Sprague—Dawley rats (Southern Farms) that were housed two to a cage for

Steroid excretion and biosynthesis, with special reference to 16-unsaturated C 19 steroids, in cases of testicular feminization and in a male pseudohermaphrodite.

ABSTRACT The concentrations of the following steriods were measured in the urine of four patients with testicular feminization (TF) syndrome and of one male pseudohermaphrodite: 5α-androst-16-en-3α-ol (3α-androstenol), 5β-androst-16-en-3α-ol (aetiocholenol), 5,16-androstadien-3β-ol (androstadienol), androsterone, aetiocholanolone, dehydroepiandrosterone (DHA) and testosterone. Elevated levels of 3α-androstenol, androsterone, aetiocholanolone and DHA were found in the urine of two TF patients studied. The third TF patient and the male pseudohermaphrodite were excreting normal amounts for adult females of the three 16-unsaturated C19 steroids, although androgen output was raised. Decreases in the excretion of these steroids occurred after removal of the testes. Administration of human chorionic gonadotrophin (HCG) and corticotrophin (ACTH) to one TF patient resulted in two- to four-fold increases in urinary 16-unsaturated C19 steroids. The excretion of the three 17-oxosteroids measured, particularly androsterone and aetiocholanolone, increased after HCG and to a lesser extent after ACTH administration. In preparations of testes removed from three TF patients androstadienol (1-8%) was formed from pregnenolone. 4,16-Androstadien-3-one (androstadienone) was obtained in greater yield (0.2–1.33%) from progesterone than from pregnenolone (0.1–0.48%) although in the histologically normal testis from the pseudohermaphrodite, pregnenolone proved to be the more efficient precursor of androstadienone. Testosterone gave rise to no 16-unsaturated C19 steroids when incubated under identical conditions. The biosynthesis of testosterone in TF testis preparations was achieved normally from both pregnenolone and progesterone, in keeping with a defect in target organ insensitivity rather than in androgen formation. The possible significance of these findings and of the formation of large amounts (19%) of DHA from pregnenolone in TF testis is discussed.

Further studies on the relation between growth hormone and corticotrophin secretion in insulin-induced hypoglycemia.

ABSTRACT Three experiments were performed to investigate the relationship between growth hormone (GH) and corticotrophin (ACTH) secretion in insulin-induced hypoglycemia: 1) Hypoglycemia was terminated 30 min after the insulin injection by acute iv administration of glucose. Four of 6 subjects showed partial suppression of plasma GH and corticosteroids (CS) responses. In no case were the rises in plasma GH and CS dissociated. 2) Dexamethasone pretreatment also suppressed plasma GH and CS responses concomitantly in 5 subjects studied. 3) Phentolamine, on the other hand, inhibited only GH response but not CS increase. Although these results were not conclusive, they favor the possibility that GH and ACTH release in insulin-induced hypoglycemia occurs by stimulation of a common center and phentolamine affects the GH secretory pathway only.

Effects of salinity, hypophysectomy and corticotrophin or branchial Na- and K-activated ATPase in the eel, Anguilla anguilla L.

Considerable evidence indicates that branchial sodium- and potassium-activated adenosine triphosphatase (Na-K-ATPase) is essential in maintaining the high sodium turn-over rate at the gills of teleosts in sea-water (SW) (Epstein, Katz & Pickford, 1967; Motais, 1970; Pickford, Pang, Weinstein, Torretti, Hendler & Epstein, 1970). Though without effect on the low freshwater (FW) levels, hypophysectomy reduces the high branchial Na-K-ATPase in SW Fundulus heteroclitus, and prolonged cortisol treatment restores normal levels (Epstein et al. 1967; Pickford et al. 1970); parallel changes occur in the sodium turn-over rate in SW F. heteroclitus after hypophysectomy and corticotrophin (ACTH) treatment (Maetz, Sawyer, Pickford & Mayer, 1967c; Maetz, Mayer, Forster & Chan, 1967b). In the European eel, Anguilla anguilla, sodium turn-over rate is higher in SW than in FW (Maetz, Mayer & Chartier-Baraduc, 1967a). In SW it is reduced by hypophysectomy (Maetz et al. 1967a) and adrenalectomy (Mayer, Maetz, Chan, Forster &

The plasma 11-hydroxycorticosteroids responseto insulin-induced hypoglycaemia in children and adolescents.

ABSTRACT The insulin tolerance test (ITT) was performed in 102 children and adolescents belonging to the following 6 groups: controls (56 subjects), pituitary insufficiency (17 patients), delayed puberty (13 patients), obesity (6 patients), idiopathic precocious sexual development (6 patients) and congenital adrenal virilization (4 patients). All subjects showed hypoglycaemia. The mean percentage of maximal reduction in the blood sugar from the fasting concentration varied from 41 to 50 in all the groups. The control subjects and the patients with delayed puberty, obesity, precocious sexual development and congenital adrenal virilization showed an increase in plasma 11-hydroxycorticosteroids (11-OHCS) to a mean peak value ranging between 20 and 25 μg/100 ml, measured 60 min after the injection of insulin. From these results it was concluded that a rise in plasma 11-OHCS to a value of 20 μg/100 ml or more after hypoglycaemic stress denotes a normal corticotrophin releasing factor (CRF) and corticotrophin (ACTH) reserve. The patients with pituitary insufficiency showed 3 types of response independent of the degree of hypoglycaemia: nine patients showed a normal response, four had a medium response and four showed no response. There was a good correlation between lack of response of plasma 11-OHCS induced by hypoglycaemia and the urinary 17-OHCS response during the metopiron test, indicating that both these tests act at the hypothalamic level. Although the rise in plasma 11-OHCS after ITT was less marked than after the lysine vasopressin (LVP) test, it is suggested that the ITT is to be preferred as a clinical screening test, as it permits concomitant evaluation of both ACTH and growth hormone reserve. Another advantage of performing the ITT before the LVP test is that it allows of the diagnosis of a hypothalamic disturbance in ACTH secretion.

Melanocyte-stimulating and corticotrophic activities in human foetal pituitary glands.

ABSTRACT Melanocyte-stimulating hormone (MSH) and corticotrophin (ACTH) activities were determined in the pituitary glands of 24 human foetuses ranging in gestational age from 11 to 23 weeks. Both hormonal activities were present in every pituitary gland examined. The foetal developmental factors were significantly correlated as were the MSH and ACTH activities. Although the mU per mg of ACTH correlated negatively with development, no correlation between MSH and development was found.

Localized pretibial myxedema: report of two cases treated with hydrocortisone by local injection.

Excerpt Reports of successful means of treatment for localized pretibial myxedema are of interest because of its close relationship with progressive exophthalmos, and the possibility that the same ...

Endogenous and exogenous vasopressin on ACTH release.

Simultaneous studies of the release of antidiuretic hormone (vasopressin, ADH) and corticotrophin (ACTH) were performed in unanesthetized trained dogs. Antidiuresis was used as the index of ADH liberation and plasma free 17-hydroxy-corticosteroid levels were used to indicate ACTH release. No correlation was observed between discharge of ACTH and release or inhibition of the release of ADH. Further studies with highly purified vasopressin showed that exogenous ADH was unable to stimulate the secretion of ACTH until a threshold of 3–7 ×103 times the dose reproducing maximal physiologic antidiuresis was exceeded. The physiological significance of the data evidencing ACTH release upon injection of vasopression is debated and questioned.

Exophthalmos of Graves' disease: a summary of the present status of therapy.

Excerpt Graves' disease may be considered to be a thyroid-pituitary syndrome. The two chief manifestations of the disorder are exophthalmos and hyperplastic goiter with hyperthyroidism. They usuall...

The differential effect of cortisone and of A.C.T.H. on mood.

It is evident from many reports published in the last four years that psychological changes can occur during the treatment of physical illness by Cortisone and corticotrophin (A.C.T.H.). There is no doubt, too, that similar mental symptoms have been occasioned by giving either of these agents in therapeutic doses. It is perhaps for this reason that most writers have not distinguished between them in this respect. Thus, the mild mood changes that often occur, and the relatively rare psychotic reactions are usually spoken of as complications of A.C.T.H. or Cortisone therapy. This implies that, in the individual case, these substances would be equivalent in their influence on the mental state; yet there are grounds for suspecting otherwise. The aetiology of these psychological reactions remains obscure, so that any evidence which serves to differentiate the psychiatric side-effects of the two drugs would be of interest.

TREATMENT OF RHEUMATOID ARTHRITIS WITH NITROGEN MUSTARD

One of us (J. D.) 1 recently reported the initial results obtained in the treatment of rheumatoid arthritis with nitrogen mustard. It was believed that this treatment might well be useful because of the well-known effect of cortisone and corticotrophin (ACTH), since, in the similar effects they produce, a certain relationship could be seen to exist between these hormones and nitrogen mustard. It is a fact that one of the most constant effects of nitrogen mustard, observed in the treatment of Hodgkin's disease, is the progressive decrease in lymphocytes —they may even disappear completely—and the decrease in the eosinophils. The same results can also be obtained with the hormones ACTH and cortisone. 2 On the other hand, Chanutin and Ludewig 3 have demonstrated that the suprarenal cortex undergoes a hyperplasia when acted upon by vesicating substances, while Karnofsky and his colleagues 4 have reproduced symptoms similar to those of the