Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our recent data show that acute and sustained hypercortisolism decreases circulating growth hormone (GH) levels in acromegaly with respect to saline infusion. It has been hypothesized that in acromegalic patients, as well as in normal subjects, short-term increases in serum cortisol levels may be able to cause an enhancement of hypothalamic somatostatin secretion, which in turn may be responsible for the glucocorticoid mediated GH inhibition. The aim of our study was to investigate the acute effects of an intravenous infusion of hydrocortisone on the GH response to growth hormone-releasing hormone (GHRH) in acromegaly. We studied 6 adult patients with active acromegaly (3 M, 3 F; mean age 60.5 +/- 4.1 years; mean body mass index 27.1 +/- 0.6 kg/m2). All the patients underwent: (1) a bolus intravenous injection of 100 mg hydrocortisone succinate in 2 ml saline, at time -60 followed by a 120-min intravenous infusion of 250 mg hydrocortisone succinate in 250 ml saline, from -60 to 60 min; (2) a bolus intravenous injection of human GHRH 1-29NH2 100 micrograms in 1 ml saline, 60 min after initiation of a 2-hour hydrocortisone infusion; (3) a bolus intravenous GHRH injection 60 min after initiation of a 2-hour saline infusion. In all of the acromegalic patients during hydrocortisone succinate infusion, GH values clearly decreased with respect to basal levels (mean nadir 47 +/- 8.6%, p < 0.05 with respect to basal levels). After GHRH injection and saline infusion all the patients showed a significant increase in GH levels (mean peak 231.5 +/- 52.8%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of hydrocortisone on the growth hormone response to growth hormone-releasing hormone in acromegaly. 801 41

The aim of this study was to investigate the mechanisms by which glucocorticoids inhibit GH secretion in man. In 10 normal volunteers subjects we compared the pattern of GHRH-induced GH release to that elicited by similar challenge given 60 min after a pretreatment with drugs affecting adrenergic and muscarinic cholinergic neurotransmission, both in basal situations and after having induced hypercortisolism. In a first study (P), synthetic GHRH [GRF-(1-29); 1 microgram/kg, i.v.] was administered 60 min after giving placebo. In other experiments, the administration of propranolol (PRO; 40 mg, orally), or clonidine (CLO; 0.300 mg, orally), or pyridostigmine (PD; 120 mg, orally) was followed by GHRH administration 60 min later. These experiments were repeated after giving a nocturnal dose of dexamethasone (DEX; 8 mg, orally at 2300 h). The administration of DEX significantly (P < 0.05) blunted the GH response to GHRH (peaks: 10.7 +/- 3.9 vs. 20.3 +/- 5.5 micrograms/L; DEX vs. P study, respectively). Conversely, either beta-adrenergic blockade (PRO), or alpha 2-adrenergic agonism (CLO), or the enhancement of muscarinic cholinergic tone (PD) significantly increased the GH response to GHRH (peaks: 43 +/- 4.6, 55.6 +/- 5.6 and 51.2 +/- 7, micrograms/L; PRO, CLO, and PD, respectively; P < 0.01 vs. P study). After nocturnal DEX administration, both PRO and CLO, but not PD, were able to reverse the inhibitory effect of DEX on GHRH-elicited GH release (peaks: 39 +/- 5.5, 25.9 +/- 3.9 and 12.9 +/- 3.1, micrograms/L; DEX + PRO, DEX + CLO, and DEX + PD, respectively). However, whereas the potentiating effect of PRO on GHRH-elicited GH release was still observed under hypercortisolism, it was lacking for both CLO and PD when these drugs were given in this situation. These data suggest that the inhibitory effect of glucocorticoid excess on GH release is due to increased hypothalamic somatostatin secretion which appears to be dependent on DEX-induced enhanced beta-adrenergic responsiveness. Moreover, the data further support a major role of hypothalamic alpha 2-adrenergic and beta-adrenergic activities in GH neuroregulation in man.
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PMID:Glucocorticoids may inhibit growth hormone release by enhancing beta-adrenergic responsiveness in hypothalamic somatostatin neurons. 809 92

To further explore the differential effects of peripherally and centrally derived hypercortisolism on neurohormonal systems implicated in the pathophysiology of mood and cognitive disturbances, we examined the cerebrospinal fluid (CSF) concentrations of immunoreactive somatostatin (IR-SRIF) in patients with Cushing's disease and major depression and the relationship of these levels to CSF immunoreactive corticotropin-releasing hormone (CRH) concentrations and urinary free cortisol excretion. In particular, since CSF SRIF levels consistently have been shown to be reduced in depression, we wished to assess whether decreased centrally directed SRIF was more likely a primary or a secondary factor in the hypercortisolism of major depression. CSF SRIF levels were significantly reduced in 11 patients with documented Cushing's disease and in 1 patient with ectopic adrenocorticotropic hormone secretion as compared with both 41 healthy volunteers (19.4 +/- 2.9 vs. 37.4 +/- 1.5 pmol/l; p < 0.01) and 28 patients with major depression (30.2 +/- 2.4 pmol/l; p < 0.05), whose CSF SRIF levels were also significantly reduced as compared with controls (p < 0.05). CSF SRIF levels in the Cushing's disease patients correlated positively with CSF CRH (r = 0.64; p < 0.025), suggesting that either the sustained hypercortisolism in these patients and/or its suppression of central CRH secretion contributed to the reduction in SRIF. A more modest but significant correlation between CSF SRIF and CSF CRH was observed in the healthy volunteers (r = 0.37; d.f. = 37; p < 0.02); in the depressed patients, no linear relationship, but rather an inverted U-shaped relationship was found which significantly fit by a quadratic function (r2 = 0.90; d.f. = 22; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebrospinal fluid immunoreactive somatostatin concentrations in patients with Cushing's disease and major depression: relationship to indices of corticotropin-releasing hormone and cortisol secretion. 809 79

An acquired defect in growth hormone secretion in mature dogs has been associated with some forms of generalised alopecia. In an attempt to elucidate the pathogenesis of the disturbance in growth hormone release, the plasma concentrations of growth hormone and insulin-like growth factor I (IGF-I) were measured in two seven-year-old poodles with alopecia and, for comparison, in two young German sheperd dogs with congenital hyposomatotropism (pituitary dwarfism). In the poodles the basal concentrations of growth hormone were low, although often above the detection limit of the assay. The concentrations of IGF-I were in the reference range for healthy poodles. No growth hormone could be detected in the plasma of the German sheperd dogs and the concentrations of IGF-I were very low. Stimulation with clonidine and growth hormone releasing hormone (GHRH) before and after repeated injections of GHRH did not result in significant increases in growth hormone concentrations in plasma. The concentrations of growth hormone in the poodles fluctuated at low levels during the test period. In the German sheperd dogs the levels of growth hormone remained unmeasurable during the stimulation tests. It was concluded that in the two poodles the basal concentrations of growth hormone were sufficient to maintain normal IGF-I concentrations, and thus the release of growth hormone was considered appropriate. Based upon measurements of urinary corticoids and a review of the literature it is suggested that the lack of a growth hormone response to stimulation was due to the enhanced release of somatostatin as a result of mild and fluctuating hyperadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Disturbed release of growth hormone in mature dogs: a comparison with congenital growth hormone deficiency. 811 57

Both exogenous and endogenous hypercortisolism result in reduced GH secretion and decreased somatic growth. However, little is known about the relation between endogenous cortisol and GH secretion under physiological or slightly disturbed conditions. To examine this, we measured and evaluated the pulsatility and circadian rhythmicity, and we cross-correlated the secretory patterns of cortisol and GH in six prepubertal patients with nonclassic 21-hydroxylase deficiency (NCCAH) and seven age-matched short-normal children. Cortisol and GH were secreted in a pulsatile fashion in both the NCCAH and control groups. The nocturnal peak cortisol increment and time-integrated area were lower in the NCCAH patients than in controls, whereas there was no difference in the total 24-h cortisol secretion between the two groups. The nocturnal increase of GH in NCCAH children, on the other hand, was associated with a significant augmentation of the pulse amplitude, whereas in control children there was an elevation of the baseline component. The cross-correlation analysis of the 24-h raw data showed that cortisol and GH were negatively correlated at brief lag times of 0-30 min, and positively correlated at long lag times of 12-12.5 h in both groups, with cortisol leading GH. The negative correlation might reflect either the negative effect of glucocorticoids on the adrenergic system, which stimulates GH secretion through GH-releasing hormone (GHRH) elevations and somatostatin (SRIH) decreases, or the absence of an inhibitory effect of CRH on SRIH. The positive correlation may reflect the positive effect of glucocorticoids on the GH gene. In conclusion, NCCAH children have a mild nocturnal cortisol deficiency compared with control children, as previously reported, and a distinct circadian pattern of pulsatile GH secretion. The hypothalamic-pituitary-adrenal (HPA) axis exerts both negative and positive influences on GH secretion, with mild disturbances in cortisol biosynthesis associated with slight alterations of GH secretion.
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PMID:Spontaneous cortisol and growth hormone secretion interactions in patients with nonclassic 21-hydroxylase deficiency (NCCAH) and control children. 863 54

For the purpose of obtaining an integral picture of anterior pituitary function in canine pituitary-dependent hyperadrenocorticism (PDH), 47 dogs with PDH and eight control dogs received combined administration of four hypophysiotropic hormones (CRH, GHRH, GnRH and TRH) and measurements were made of ACTH, cortisol, GH, LH, PRL and TSH. Basal plasma levels in 47 dogs with PDH were higher for ACTH, cortisol and PRL, lower for GH, and not different for LH (n = 25 noncastrated dogs) and TSH compared with controls (n = 8). In dogs with PDH the responses to combined hypophysiotropic stimulation, measured as increment and area under the curve (AUC), were not different for ACTH, lower for GH and TSH (increments and AUC) and higher for cortisol (increments), LH (AUC, n = 25 noncastrated dogs) and PRL (increments and AUC) than in controls. We conclude that pituitary function is altered in several respects in dogs with PDH. 1) In spite of persisting hypercortisolemia and the neoplastic transformation of the corticotropic cells, these cells usually remain responsive to combined hypophysiotropic stimulation. 2) Basal plasma GH concentrations and GH responsiveness in the combined stimulation test are decreased, probably as a result of the glucocorticoid-induced increase in somatostatin tone. 3) Plasma PRL concentrations and the PRL response to stimulation are increased, probably as a result of cosecretion with ACTH by the transformed corticotropic cells. 4) Despite the well known effect of glucocorticoids of decreasing circulating concentrations of gonadal steroids and thyroxine, the basal plasma concentrations of LH and TSH remain unchanged and there is a tendency to hyperresponsiveness to stimulation for LH and hyporesponsiveness for TSH. The most likely explanation for these changes is a dual effect of glucocorticoids: a direct effect on the gonads and thyroids and/or the transport and metabolism of their secretory products, and an influence on the sensitivity of the feedback control at the hypothalamic-pituitary level.
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PMID:Alterations in anterior pituitary function of dogs with pituitary-dependent hyperadrenocorticism. 937 28

A 33 year old woman was investigated for an atypical case of Cushing's syndrome with suppressed early morning plasma cortisols. Chronic hypercortisolism was confirmed by classical biological criteria (24 h urinary cortisol excretion, dexamethasone suppression tests); more detailed dynamic and pharmacological tests revealed unanticipated features: spontaneous circadian plasma cortisol variations showed post prandial peaks; they could be induced by oral--but not intravenous--glucose tolerance tests, and were inhibited by the concomitant administration of Sandostatin (a somatostatin analog). Adrenal CT scan identified a 2 cm unilateral adenoma with ipsilateral and contralateral atrophy. Surgical removal of the tumor cured the hypercortisolism with hypocortisolism. Comparative analysis of the tumoral and normal tissues showed that only the former responded in vitro to GIP (Gastric Inhibitory Polypeptide) and contained the specific mRNA of the GIP receptor. This case illustrates a new pathophysiological mechanism of tumorigenesis due to the aberrant expression of a seven transmembrane domain receptor in a tumoral tissue. The nature of the given receptor induced a particular clinical phenotype related to food intake.
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PMID:[Aberrant expression of the GIP (Gastric Inhibitory Polypeptide) receptor in an adrenal cortical adenoma responsible for a case of food-dependent Cushing's syndrome]. 1033 44

Pituitary diseases are relatively common entities in the general population. They include pituitary adenomas and hypopituitarism. Pituitary tumours can cause symptoms of mass effect and hormonal hypersecretion that can be reversed with surgical resection or debulking of the adenoma, radiotherapy, or medical treatment. Transsphenoidal adenomectomy is the treatment of choice for acromegaly, Cushing's disease, gonadotropin-secreting tumours; and thyrotropin (TSH)-secreting adenomas. Pituitary irradiation and medical therapy are secondary options. Conversely, medical treatment is the primary choice for prolactinomas. Dopamine agonists are very effective in the treatment of prolactin (PRL)-secreting tumours, with rates of control as high as 80 to 90% for microprolactinomas (< 10 mm) and 60 to 75% for macroprolactinomas (> or = 10 mm). Somatostatin analogues have also shown efficacy in patients with acromegaly who have not responded to surgery or in patients with TSH-secreting adenomas who have not improved with surgery and radiotherapy. In patients with Cushing's disease, who are not cured surgically or who relapse after pituitary adenomectomy and irradiation, steroidogenic inhibitors can be an efficient method of controlling the hypercortisolism. Pituitary insufficiency is the partial or complete loss of the anterior hypophyseal function, which is due to hypothalamic or pituitary disease. Although the classic sequence of loss of pituitary secretion is growth hormone (GH), gonadotropins, TSH, and corticotropin (ACTH), the order to begin the replacement therapy of the deficient hormone(s) is cortisol, thyroxine, androgens/estrogens and, if necessary, GH. There are multiple preparations that can be used to achieve clinical and biochemical improvement. In general, the hormone replacement therapy is lifelong.
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PMID:Pituitary disorders. Drug treatment options. 1071 1

The preoperative evaluation and safe anesthetic treatment of patients with endocrine gland tumors mandate an understanding of the physiologic dysfunctions attributable to these tumors. Some patients will exhibit various signs and symptoms characteristic of the MEN syndromes. In the patient with acromegaly, a fiberoptic-guided intubation of the trachea to secure the airway before induction of general anesthesia must be anticipated. Anesthetic treatment of the patient with hyperadrenocorticism requires knowledge of the physiologic effect of excess cortisol. In the patient with severe hyperparathyroidism, we attempt to correct the markedly elevated plasma calcium levels and maintain adequate hydration and urine output perioperatively. Following thyroidectomy for MCT, 2 potential problems of concern are upper airway obstruction and aspiration resulting from injury (unilateral or bilateral) to the recurrent laryngeal nerve and the superior laryngeal nerve, respectively. The major focus during excision of an insulinoma is prevention of wide swings in blood glucose concentrations. In the gastrinoma patient, the anesthesiologist not only must correct any intravascular fluid volume deficit or electrolyte imbalance but must also consider the patient to have a full stomach at the time of anesthetic induction. Correction of hypokalemia and control of hypertension may be required in the preoperative preparation of the patient with an adrenal cortex tumor. Preoperative alpha-adrenergic blockade must be initiated in the patient with a pheochromocytoma to prevent dangerous elevations in blood pressure during anesthesia and surgery for the tumor's removal. Vasodilators with rapid onset and short duration are used to treat intraoperative hypertension. After ligation of the tumor's blood supply, falls in blood pressure may require treatment with fluids and vasopressors. Carcinoid syndrome patients should be treated with somatostatin to prevent stimuli such as anxiety, abdominal scrubbing, or tumor manipulation from precipitating severe hypotension, hypertension, bronchospasm, or tachycardia. In both pheochromocytoma and carcinoid patients, a smooth anesthetic induction and tracheal intubation plus avoidance of drugs that release histamine or activate the sympathetic nervous system may also prevent intraoperative crises.
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PMID:Anesthetic implications for surgical patients with endocrine tumors. 1081 14

The stress system coordinates the adaptive response of the organism to real or perceived stressors. The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine/ autonomic (LC/NE) systems and their peripheral effectors, the hypothalamic-pituitary-adrenal (HPA) axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. Thus, CRH and the LC/NE system stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the amygdala, which are responsible for the generation of fear. Hypothalamic CRH plays an important role in inhibiting gonadotropin-releasing hormone secretion during stress, while via somatostatin it also inhibits growth hormone, thyrotropin-releasing hormone and thyrotropin secretion, suppressing thus reproduction, growth and thyroid function. Glucocorticoids directly inhibit pituitary gonadotropin, growth hormone and thyrotropin secretion and make the target tissues of sex steroids and growth factors resistant to these substances. In addition, glucocorticoids stimulate hepatic gluconeogenesis, and inhibit or potentiate insulin actions on skeletal muscle and adipose tissue respectively, ultimately promoting visceral adiposity and the metabolic syndrome. Glucocorticoids also have direct effects on the bone, inhibiting osteoblastic activity and causing osteoporosis. Obese subjects with psychiatric manifestations ranging from those of melancholic depression to anxiety with perception of 'uncontrollable' stress, frequently have mild hypercortisolism, while carefully screened obese subjects with no such manifestations are eucortisolemic. The former may have stress-induced glucocorticoid-mediated visceral obesity and metabolic syndrome manifestations, which in the extreme may be called a pseudo-Cushing state that needs to be differentiated from frank Cushing syndrome. Stress-induced hypercortisolism and visceral obesity and their cardiovascular and other sequelae increase the all-cause mortality risk of affected subjects by 2-3-fold and curtail their life expectancy by several years.
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PMID:The role of stress and the hypothalamic-pituitary-adrenal axis in the pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes. 1099 9


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