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)

The contents of immunoreactive somatostatin (IR-SRIF) and beta-endorphin (IR-beta-EP) in 12 brain regions were examined in rats exposed neonatally to propylthiouracil (PTU) through the mother's milk. Since the dose of PTU used in this study is lower than the usual dose employed to induce hypothyroidism, a milder form of neonatal hypothyroidism resulted. This conclusion is supported by the only mild subnormal growth of rats to adulthood and serum T4 and T3 concentrations in the normal range. Adult rats treated with PTU neonatally had significantly higher IR-SRIF contents in several brain regions compared to controls, whereas IR-beta-EP levels were not significantly different (significant increase only in the thalamus) in most regions. The results indicate that even mild hypothyroidism during early postnatal development causes permanent impairment of brain function, which manifests itself in part by an altered brain content of IR-SRIF.
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PMID:Immunoreactive somatostatin and beta-endorphin content in the brain of mature rats after neonatal exposure to propylthiouracil. 612 58

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment on body temperature and serum and tissue levels of thyroid hormones, glucose, glucagon, insulin, and somatostatin were investigated. Within 7 days following TCDD administration (45 micrograms/kg), rats exhibited hypothyroidism compared to pair-fed controls and rats fed ad libitum. Body temperature was maintained in the pair-fed and ad libitum-fed controls but was significantly decreased in TCDD-treated rats at 2 days. Within 2 weeks of the administration of 90 micrograms TCDD/kg, body temperature was below 35 degrees C with the lowest mean value of 34.5 degrees C recorded on Day 16. Mean body temperatures for control rats ranged from 36.8 to 37.5 degrees C. One week after TCDD administration (45 micrograms/kg), serum thyroxine (T4) declined to 46% of pair-fed controls. The decreased free-thyroxine index indicated that the measured decrease in thyroxine reflected decreased hormone concentrations as opposed to altered protein binding. Hypoglycemia occurred in TCDD-treated rats subsequent to hypothyroxinemia and hypothermia, but it did not develop in the pair-fed controls. At 1 week after administration of 45 micrograms TCDD/kg, serum and pancreatic insulin levels were reduced to 25 and 76% of ad libitum-fed controls, respectively. Hypophagia was determined to be responsible for the decreased growth rate and hypoinsulinemia but did not account for hypothyroxinemia, hypothermia, and hypoglycemia following the administration of TCDD. No significant alterations were detected in serum glucagon or in pancreatic, hepatic, or serum somatostatin levels. Decreased somatostatin in the gastric antrum coincided with a 29% increase in stomach dry weight. The delayed toxicity of TCDD may result, in part, from these hormonal alterations.
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PMID:Hypothyroxinemia and hypothermia in rats in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin administration. 613 53

The respiratory stimulants caffeine and theophylline are able to control apneic spells in premature newborns. However both substances have goitrogenic properties in rats on low-iodine diet. They lower T4 serum levels and inhibit TSH- and GH-release probably by enhancing hypothalamic somatostatin secretion. The retrospective study described here was carried out in an attempt to clarify whether treatment of premature children with methylxanthines has adverse effects on thyroid function. The results are as follows: 1) There is no significant correlation between caffeine- and theophylline-concentrations and circulating T4 levels in single blood specimen of unselected premature infants. 2) In none of the infants was a low T4-serum value accompanied by a rise in serum TSH during methylxanthine treatment. Thus methylxanthines are not associated with the induction of primary hypothyroidism but the possibility of tertiary hypothyroidism cannot be excluded. In order to avoid adverse effects on thyroid function the lowest therapeutically active dose should be chosen.
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PMID:T4 levels in methylxanthine-treated premature newborns. 667 76

Primary hypothyroidism and partial primary adrenocortical deficiency (isolated glucocorticoid deficiency) were diagnosed in an 8-year-old spayed female boxer dog, presented because of progressive symmetrical truncal alopecia, lethargy, and intolerance to cold. The diagnosis was based upon the combination of low, non-TSH-responsive concentrations of plasma thyroxine and low urinary excretion of corticoids together with high plasma concentrations of ACTH. Normal suppressibility of ACTH concentrations by a low dose of dexamethasone indicated an intact feedback system. Plasma growth hormone levels were elevated, most probably because somatostatin release was depressed by the glucocorticoid deficiency. The dog improved during oral replacement therapy with thyroxine until death ensued after 9 months as a result of intercurrent disease. Autopsy revealed thyroid atrophy and lymphocytic adrenalitis with complete destruction of the zona fasciculata and zona reticularis of the adrenal cortex. The combination of primary hypothyroidism and primary adrenocortical deficiency in this dog is identical to the entity known as type II polyglandular autoimmunity or Schmidt's syndrome in humans. The adrenocortical insufficiency remained confined to glucocorticoid deficiency during the observation period; on no occasion did electrolyte concentrations in the plasma reach values suggestive of mineralocorticoid deficiency.
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PMID:Polyglandular deficiency syndrome in a boxer dog: thyroid hormone and glucocorticoid deficiency. 757 Dec 81

1. Fourteen days after hypothyroidism was induced either by propylthiouracil (PTU) treatment or by thyroidectomy, the serum thyrotropin (TSH) responses to morphine (5 or 20 mg/kg bw), ether stress (30 min) and cold exposure (60 min) were compared with those in normal rats. 2. The decrease in serum TSH levels after morphine and ether stress found in the normal rats were abolished or much reduced respectively. 3. The increase in serum TSH in response to cold exposure and the diurnal rhythm of serum TSH (lower level at night) were also absent in the hypothyroid rat. 4. The stimulating effects of low dose of thyrotropin releasing hormone (TRH) and the inhibitory effects of somatostatin and apomorphine were completely abolished, while the stimulating effects of a high dose of TRH were much reduced in the hypothyroid rat. 5. These results indicate that in the hypothyroid rat the effect of a lack of negative feedback action of thyroid hormone predominates, and that hypothalamic factors are probably unimportant in the regulation of TSH secretion.
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PMID:Effect of environmental and hypothalamic factors on thyrotropin secretion in the hypothyroid rat. 809 28

We investigated whether the impaired GH secretion of hypothyroid patients could be due to an increase in hypothalamic somatostatinergic tone. Twenty-four patients with primary hypothyroidism [20 females and 4 males; mean age (+/- SE), 47.5 +/- 2.7 yr] and 20 normal subjects (17 females and 3 males; age, 47.6 +/- 3.0 yr) were studied. In the first group of 12 hypothyroid patients, administration of pyridostigmine, a cholinergic agonist drug (120 mg, orally, at -60 min), notably increased GH responses to GH-releasing hormone (GHRH; 1 microgram/kg, iv, at 0 min; peak GH levels for pyridostigmine plus GHRH vs. placebo plus GHRH, 16.6 +/- 4.9 vs. 6.0 +/- 1.8 micrograms/L; P < 0.01). The GH responses to pyridostigmine plus GHRH, however, were considerably lower than those in 10 normal subjects (peak GH levels, 53.0 +/- 3.5 micrograms/L; P < 0.001). In the second group of 12 hypothyroid patients, arginine infusion (30 g, iv, from 0-30 min) markedly increased the GH responses induced by GHRH administration (1 microgram/kg, iv, at 0 min; peak GH levels for arginine plus GHRH vs. placebo plus GHRH, 30.6 +/- 4.7 vs. 5.3 +/- 1.0 micrograms/L; P < 0.001). However, GH release after GHRH plus arginine was greater in 10 normal subjects than in the hypothyroid patients (peak GH levels, 50.9 +/- 5.3 micrograms/L; P < 0.001). Pyridostigmine and arginine inhibit hypothalamic somatostatin tone. The stimulatory effect of both agents on GHRH-induced GH release indicates that reduced GH secretion in hypothyroidism can be reversed to a considerable extent by inhibiting hypothalamic somatostatinergic tone. The relatively greater potency of arginine compared to pyridostigmine suggests that hypothyroid patients may have an impairment of the cholinergic pathways. Furthermore, these data show that hypothyroid patients have a somatotrope secretory capacity much greater than previously thought.
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PMID:Evidence against depletion of the growth hormone (GH)-releasable pool in human primary hypothyroidism: studies with GH-releasing hormone, pyridostigmine, and arginine. 810 70

Octreotide, as well as endogenous somatostatin, inhibits GH and TSH secretion. The drug is employed in the medical therapy of acromegaly. We studied the effects of a long-term (1-120 months; median 12 months) therapy with octreotide (300 micrograms/day) given in 3-times intermittent s.c. administration or in pulsatile s.c. (25 micrograms/120 min) way, upon the pituitary-thyroid axis. Thirteen patients (11 with normal thyroid function, 1 with secondary hypothyroidism, 1 with toxic goiter) with active acromegaly were studied. In the euthyroid patients no significative variations in both TSH levels and thyroid hormones were found during octreotide therapy. In the non-euthyroid patients octreotide did not induce changes in the dosages of drugs acting to thyroid function. The 24-hour IC-TSH levels did not show any variation during octreotide. TSH response to TRH was reduced (P < 0.05) during octreotide therapy. No correlation among TSH, IGF-I and GH levels was observed. Long-term treatment of acromegaly with octreotide reduces TSH response to TRH but do not interfere with both 24-hour IC-TSH levels and thyroid function.
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PMID:[Behavior of the pituitary-thyroid axis in acromegalic subjects during prolonged intermittent and pulsatile treatment with octreotide]. 818 83

Thyroid hormones are important to growth in mammals and have been shown to rapidly stimulate the rate of GH gene transcription. In this study, we investigated whether thyroid hormones modulate GH secretion through their effects on the gene expression of GRF, somatostatin (SS), GRF receptor, and receptor subtype 2 for SS (SSTR2). Male adult Sprague-Dawley rats were rendered hypothyroid with a single injection of propylthiouracil followed by methimazole in drinking water (0.02%) for 1 day to 12 weeks. Total RNA extracted from the anterior pituitary and hypothalamus was analyzed by Northern hybridization. GH messenger RNA (mRNA) level in the anterior pituitary was significantly reduced in the hypothyroid animals (P < 0.0001 vs. controls for all treatment duration > or = 1 week). An increase in hypothalamic GRF mRNA level, by 2- and 4-fold, respectively, was seen after 3 and 12 weeks of antithyroid treatment (both P < 0.001 vs. controls). Hypothalamic GRF content, studied in 12-week hypothyroid rats only, was decreased compared with controls (P < 0.05). A reduction in pituitary GRF receptor mRNA level was observed after 1 week of antithyroid treatment (P < 0.01 after 1 week, P < 0.001 after 3 weeks). Total hypothalamic SS content and SS mRNA level in hypothalamic fragments consisting predominantly of the paraventricular and periventricular nuclei became significantly decreased (P < 0.05 and P < 0.005 respectively) after 12-weeks of antithyroid treatment. The reduction in SS gene expression in the periventricular nuclei was confirmed by in situ hybridization. No significant change in the mRNA level of pituitary SSTR2 was observed up to 12 weeks of antithyroid treatment. In conclusion, we have demonstrated a reduction in the gene expression of GRF receptor and SS in the hypothyroid rat. Our results suggest that the changes in hypothalamic GRF and SS gene expression in hypothyroid rats may be compensatory in nature and are likely to be secondary to the reduction in GH synthesis and secretion in these animals. The reduction in basal and GRF-stimulated GH secretion in hypothyroidism can be explained by the observed reduction in GH and GRF receptor gene expression.
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PMID:Gene expression of hypothalamic somatostatin, growth hormone releasing factor, and their pituitary receptors in hypothyroidism. 859 84

Growth hormone-releasing peptides (GHRPs) are synthetic, non-natural peptides endowed with potent stimulatory effects on somatotrope secretion in animals and humans. They have no structural homology with GHRH and act via specific receptors present either at the pituitary or the hypothalamic level both in animals and in humans. The GHRP receptor has recently been cloned and, interestingly, it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. The mechanisms underlying the GHRP effect are still unclear. At present, several data favor the hypothesis that GHRPs could act by counteracting somatostatinergic activity both at the pituitary and the hypothalamic level and/or, at least partially, via a GHRH-mediated mechanism. However, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. GHRP-6 was the first hexapeptide to be extensively studied in humans. More recently, a heptapeptide, GHRP-1, and two other hexapeptides, GHRP-2 and Hexarelin, have been synthesized and are now available for human studies. Moreover, non-peptidyl GHRP mimetics have been developed which act via GHRP receptors and their effects have been clearly demonstrated in animals and in humans in vivo. Among non-peptidyl GHRPs, MK-0677 seems the most interesting molecule. The GH-releasing activity of GHRPs is marked and dose-related after intravenous, subcutaneous, intranasal and even oral administration. The effect of GHRPs is reproducible and undergoes partial desensitization, more during continuous infusion, less during intermittent administration: in fact, prolonged administration of GHRPs increases IGF-1 levels both in animals and in humans. The GH-releasing effect of GHRPs does not depend on sex but undergoes age-related variations. It increases from birth to puberty, persists at a similar level in adulthood and decreases thereafter. By the sixth decade of life, the activity of GHRPs is reduced but it is still marked and higher than that of GHRH. The GH-releasing activity of GHRPs is synergistic with that of GHRH, is not affected by opioid receptor antagonists, such as naloxone, and is only blunted by inhibitory influences, including neurotransmitters, glucose, free fatty acids, gluco corticoids, recombinant human GH and even exogenous somatostatin, which are known to almost abolish the effect of GHRH. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states such as in acromegaly, anorexia nervosa and hyperthyroidism. On the other hand, their good GH-releasing activity has been shown in some but not in other somatotrope hyposecretory states. In fact, reduced GH responses after GHRP administration have been reported in idiopathic GH deficiency as well as in idiopathic short stature, in obesity and in hypothyroidism, while in patients with pituitary stalk disconnection or Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. In short children an increase in height velocity has also been reported during chronic GHRP treatment. Thus, based on their marked GH-releasing effect even after oral administration, GHRPs offer their own clinical usefulness for treatment of some GH hyposecretory states.
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PMID:Growth hormone-releasing peptides. 918 61

Patients with beta-thalassemia often present with abnormalities in growth and other endocrine functions. Growth hormone (GH) secretion is controlled via somatostatin and growth hormone releasing hormone (GHRH). Recently, Hexarelin, a new potent GH secretagogue (His-D-2-Methyl-Trp-Ala-Trp-D-Phe-Lys-NH2), was synthesized. Our study was designed to assess and compare its efficacy as a GH secretagogue to GHRH 1-29 in beta-thalassemia. Eighteen patients, regularly transfused and chelated, were studied; 11 were short statured. None had diabetes mellitus, hypothyroidism, hypopara-thyroidism or major organ failure. We measured GH at 0, 30, 60, 90, 120 min after GHRH 1-29 or Hexarelin administration. Hexarelin p.o. or i.v. evoked a brisk rise of serum GH which was significantly higher (p < 0.01) than that induced by GHRH 1-29 i.v. In conclusion, Hexarelin has greater GH releasing capacity than GHRH 1-29 at 1 microgram/kg i.v. and can thus be viewed as a potential therapeutic agent in GH deficient states.
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PMID:Growth hormone release by the novel GH releasing peptide hexarelin in patients with homozygous beta-thalassemia. 936 40


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