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)

Ten patients (seven women, three men) with active acromegaly, five previously treated and five newly diagnosed, were included in an open-label prospective trial of 3 daily subcutaneous injections of the long-acting somatostatin analogue SMS 201-995 (Sandostatin) at increasing doses in order to obtain maximum growth hormone (GH) suppression. Four patients had received surgery, radiotherapy or bromocriptine. SMS 201-995 doses were increased in a stepwise fashion from 100 micrograms every 8 h (three times daily) to 200, 300 and finally 500 micrograms three times daily at monthly intervals if mean serum GH values failed to decrease to undetectable levels in over 75% of the samples. The optimal dose was maintained for up to 28 months. Significant clinical improvement of headache, soft tissue swelling, facial features, hyperhidrosis and paraesthesia occurred in all patients. Mean 12-h GH levels were significantly suppressed in four patients and fell to normal values in four. Suppression of GH levels was not achieved in two patients. Comparison of the mean interindividual GH values shows that the optimal efficacious dose is 100 micrograms t.i.d. in 7/10 patients. Somatomedin-C (SM-C) was also significantly reduced to below 50% of pretreatment levels in nine patients in whom it was measured. The subsequent increments of SMS 201-995 up to 500 micrograms three times daily did not produce further clinically relevant GH or SM-C suppression. Pituitary tumour shrinkage occurred in five patients. Thyroid function remained normal. Impaired glucose tolerance occurred in four patients. Side-effects (diarrhoea, abdominal discomfort) were mild and transient. Asymptomatic gallstones occurred in three patients on 1500 micrograms/day and one patient on 600 micrograms/day after 6-12 months treatment. This dose-finding study shows that 100 micrograms three times daily SMS 201-995 is an effective therapy for most of the acromegalic patients we treated.
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PMID:Clinical and biochemical effects of incremental doses of the long-acting somatostatin analogue SMS 201-995 in ten acromegalic patients. 220 Jun 20

Thyroid C-cell reactivity to 15 monoclonal antibodies raised against a series of pancreatic islet cells (H[human]ISL,B[bovine]ISL and R[rat]ISL) was evaluated using an indirect immunoperoxidase technique on frozen thyroid sections. Of the monoclonal anti-islet cell antibodies, five reacted specifically with bovine C-cells or human hyperplastic and neoplastic C-cells but not with follicular cells. Two monoclonal antibodies of the bovine series showed strong immunoreactivity with C-cells and only a weakly positive immunostaining of follicular cells. Five monoclonal antibodies reacted with both thyroid C-cells and follicular cells, whereas 3 monoclonal anti-islet cell antibodies did not strain any cell type of the thyroid. In human medullary carcinomas, calcitonin- and somatostatin-producing neoplastic cells were immunoreactive with the same monoclonal antibodies as were normal human C-cells. The protein bands identified by the monoclonal antibodies in human medullary carcinomas had the same molecular weight as those from pancreatic islet extracts. Our study demonstrates the presence of similar differentiation antigens on thyroid C-cells and pancreatic islet cells; this further illustrates common modes of differentiation and specialisation of these embryologically different members of the dispersed neuroendocrine system. The crossreactivity of seven of the monoclonal antibodies investigated with follicular epithelium of the thyroid suggests the existence of common antigenic determinants in different endocrine organs and may partly explain the multiple organ autoimmune response found in patients with polyendocrine diseases.
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PMID:Reactivity of monoclonal islet cell antibodies on normal hyperplastic and neoplastic thyroid C-cells. 257 Jun 33

Thyroid glands from 64 bulls with hyperplastic and/or neoplastic changes in ultimobranchial remnants and in the parafollicular (C) cell system were studied structurally and with immunohistochemical methods. Antibodies against thyroglobulin, calcitonin, somatostatin, and neurotensin were used to detect these substances. Two different types of changes were observed. One change was hyperplasia and neoplasia of the ultimobranchial remnants that affected all their epithelial constituents. These included ultimobranchial follicles, cysts and tubules, as well as solid nests formed by basophilic immature cells which were functionally undifferentiated and unreactive with all the antisera used. Differentiated follicular cells that formed thyroid follicles and cribriform structures with immunohistochemical evidence of thyroglobulin production were also found. In addition, differentiated light and cytoplasm-rich cells were scattered in the walls of the thyroid follicles, ultimobranchial follicles, cysts and tubules as well as in the solid component. They were argyrophilic and reacted with antibodies against calcitonin and somatostatin. The other change was a diffuse or multifocal hyperplasia of the parafollicular (C) cells that was present in other parts of the thyroid parenchyma--sometimes with gradual development of sclerotic tumors that had been exclusively formed by these cells. They corresponded to light cytoplasm-rich cells seen in the ultimobranchial lesions that were argyrophilic and harbored material reactive with antibodies against calcitonin and/or somatostatin. The changes observed in the parafollicular cell system resembled lesions seen in human thyroid glands with the familial variant of medullary carcinoma as well as those reported in thyroid glands of patients with longstanding hypercalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperplastic and neoplastic changes in ultimobranchial remnants and in parafollicular (C) cells in bulls: a histologic and immunohistochemical study. 285 34

Thyroid hormone effects on brain somatostatin-like immunoreactivity (SRIF-LI) were studied in an in vitro model system. Serum was removed from the nutrient culture medium of fetal day-18 rat cerebral cortex cells maintained in primary, long-term, dispersed monolayer culture. Chronic administration of either T3 or T4 in serum-free medium was associated with suppressed release of SRIF-LI into the culture medium (36-43 h accumulation), cell content of peptide and acute release in response to potassium-induced depolarization. Suppression was dose-dependent with an IC50 of less than 1 nM for T3. The most dramatic effects were observed for K+-induced release. Thirty-five to 50% suppression was typically observed with T3 at a near maximum dose (3 nM). Reverse T3 and diiodotyrosine were less potent and effective than T3. TRIAC and diiodothyronine also possessed significant suppressive activity. T3 suppression of release depended on duration of pretreatment. Administered for less than 16 h, T3 failed to significantly suppress K+-induced release, but significant suppression was observed for pretreatment periods of 16 h or longer. Indirect fluorescent immunohistochemical examination revealed a reduction in the number of cells positively stained for SRIF-LI in T3-treated dishes relative to controls. Upon removal of T3 and subsequent recovery in serum supplemented medium for 24 h, T3-treated and control cells exhibited similar levels of SRIF-LI release and cell content. T3-treated and control cells incorporated [3H] leucine into trichloracetic acid precipitable counts to similar extents. Dexamethasone and several sex steroids failed to modify the effects of T3 and did not independently influence SRIF-LI levels. Acute cycloheximide administration did not reverse T3 effects. The data indicate that primary brain cell cultures may be useful models to examine direct peripheral hormone actions on nervous tissue. Thyroid hormones suppress SRIF-LI levels in a dose, time and structure-dependent manner, which appears to be reversible. The findings are consistent with a possible integration of peripheral hormone and brain peptide physiology.
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PMID:Thyroid hormones reversibly suppress somatostatin secretion and immunoreactivity in cultured neocortical cells. 285 80

The median eminence content of immunoreactive somatostatin (IRS) was measured by radioimmunoassay in 107 male albino rats, who were either hypothyroid after surgical thyroidectomy (N = 38), hyperthyroid following a subcutaneous implant of 5 mg of L-thyroxine (N = 36), or otherwise untreated (N = 33). Thyroid function was assessed by determining plasma levels of T4 and TSH from trunk blood obtained at the time of decapitation. Subgroups of animals from the 3 groups were killed either before (1800 hr), during (2200, 0200, 0400 hr), or after the dark portion of their 14:10 LD photoperiod. Although no changes in median eminence IRS content were found throughout the period of study within any of the 3 groups, hypothyroid animals (297.23 +/- 13.47 ng per ME; 620.41 +/- 58 ng IRS/mg protein) had a significantly lower median eminence IRS concentration than untreated rats (355.86 +/- 16.55 ng of IRS per ME, P less than 0.01; 906.86 +/- 96.38 ng IRS/mg protein, P less than 0.05) and hyperthyroid animals (384.12 +/- 14.67 ng per ME, P less than 0.001; 874.1 +/- 104.5 ng IRS@mg protein, P less than 0.05). It is concluded, that the feedback of thyroid hormones on the hypothalamic-pituitary axis during thyroid hormone excess in vivo, contrary to what occurs in hypothyroidism, is probably independent of hypothalamic somatostatin.
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PMID:Nighttime immunoreactive somatostatin content of the median eminence in hypo- and hyperthyroid rats. 285 41

The effects of thyroid hormone deprivation and of subsequent replacement therapy on growth hormone (GH) secretion were investigated in unrestrained unanesthetized rats. Male rats were thyroparathyroidectomized (TPTX) 5 weeks prior to plasma sampling for GH assay, or to decapitation for evaluation of hypothalamic somatostatin (SRIF) content and in vitro SRIF and GH release. Thyroid hormone deprivation suppressed pulsatile GH secretion as well as GH release induced by clonidine (150 micrograms/kg). Treatment of TPTX rats with small doses of triiodothyronine (T3) restored an episodic pattern of GH secretion, but with lower peak values than controls, as well as the GH response to clonidine. Thyroid deprivation induced a 92-fold decrease in GH release from the pituitary; however, the ratio between GH release and GH content was similar in TPTX and normal rats, and human pancreatic growth hormone-releasing factor (GRF) (3 X 10(-8) M) was still able to stimulate residual GH release by hemipituitaries from TPTX rats in a manner similar to that in euthyroid controls (295 and 254% stimulation, respectively). Thyroid deprivation or T3 replacement did not modify SRIF content in the hypothalamus or other brain structures tested. The capacity of K+ depolarization to release SRIF in vitro from the hypothalamus was not modified by TPTX. These findings indicate that thyroid hormones are necessary to maintain both pulsatile and induced GH secretion in unanesthetized rats. In addition they suggest that impairment of GH secretion in thyroidectomized rats does not depend upon changes in the hypothalamic SRIF regulation of the hormone but could be dependent on a defect in GRF release and/or, most probably, GH synthesis directly at the pituitary level.
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PMID:Thyroidectomy abolishes pulsatile growth hormone secretion without affecting hypothalamic somatostatin. 286 82

The effect of aging on the formation of C cell follicles was examined in the thyroid gland of guinea pigs at various ages ranging from 1 to 29 months. The C cell follicles were demonstrated with the immunoperoxidase methods by using anticalcitonin and antisomatostatin antisera and with PAS reaction. They were already detected in 1-month-old guinea pigs but in low number. Thyroid glands from 1- to 14-month-old animals contained only a small number of C cell follicles and did not reveal the age-related increase. In aged guinea pigs (20- to 29-month-old), a dramatic increase of C cell follicles was found, about 13 times as high as the number of other age groups. The C cell follicles through all age groups were present in large clusters of C cells. In the aged guinea pigs, nodular large aggregates of C cells regarded as C cell hyperplasia occurred and numerous C cell follicles were formed in the large cell aggregates. Thus, the conspicuous increase of C cell follicles in aged animals was associated with a proliferative abnormality of C cells. The C cells forming follicles showed moderate to weak immunoreactivity for calcitonin, whereas they showed very intense immunoreactivity for somatostatin. In addition, the colloidlike and flocculent materials stored in the follicular lumina, which were consistently PAS-positive, were weakly immunoreactive to somatostatin but nonreactive to calcitonin.
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PMID:Age associated increase of C cell follicles in guinea pig thyroid glands. 287 95

Current treatment of acromegaly (surgery, radiation, and bromocriptine) is often unsatisfactory, and a sizeable proportion of patients with this disease continue to have GH hypersecretion after all therapeutic modalities have been exhausted. Fifteen patients with active acromegaly (8 previously treated and 7 newly diagnosed) were treated with the long-acting somatostatin analog SMS 201-995 (Sandoz; 50-250 micrograms, sc, every 6-8 h for up to 21 months). The mean daily plasma GH concentration was significantly suppressed in 13 patients, and it became normal in 10. Two patients, however, did not have GH suppression by SMS 201-995 treatment alone; in 1, a significant decline in mean daily GH was achieved after the addition of bromocriptine. As expected, suppression of GH secretion was associated with normalization of plasma somatomedin-C values and significant clinical improvement. Plasma GH responses to synthetic GHRH-(1-44) and TRH were either abolished or blunted by SMS 201-995. Thyroid function remained normal, and glucose tolerance did not change. Significant shrinkage of pituitary tumors occurred in 7 previously untreated and 2 previously treated patients. Side-effects were minimal. SMS 201-995 is an effective agent for the treatment of acromegaly. Further studies are necessary to establish guidelines for identification of non-responders and to examine the effect of preoperative tumor shrinkage on subsequent surgical outcome.
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PMID:Treatment of acromegaly with the long-acting somatostatin analog SMS 201-995. 289 20

Thyroid hormone (TH) action on somatostatin (SRIF) secretion and synthesis by fetal rat brain cells in culture was studied. Cortical and hypothalamic brain cells were maintained as monolayer cultures for 7-10 days. T3, T4, and [3H] phenylalanine [( 3H]Phe) (40 microCi/plate) were added simultaneously for 48 h. Alternately, cultures were pulse labeled with [3H] Phe for only the last 3 h, after being exposed to TH for 45 h. 3H-Labeled SRIF-like material [( 3H]IR-SRIF) was purified by immunoaffinity chromatography and further characterized by gel filtration in Bio-Gel P-10. Total protein synthesis was determined by the incorporation of [3H]Phe into trichloroacetic acid precipitable proteins. Forty eight-hour T3 treatment had a biphasic effect on secretion of IR-SRIF by both cortical and hypothalamic cells. In cortical cells, low doses of T3 (10(-11) M) significantly increased (P less than 0.01) and high T3 doses (10(-7) M) significantly decreased (P less than 0.05) total IR-SRIF (nanograms per plate); control: 2 +/- 0.25; T3 (10(-11) M): 3 +/- 0.3; T3 (10(-7) M): 1.3 +/- 0.1. Similarly, T4 had a significant stimulatory action at 10(-9) M, being inhibitory at 10(-7) M (picograms/plate); control: 290 +/- 20 T4 (10(-9) M): 510 +/- 40; T4 (10(-7) M): 201 +/- 10. When [3H]Phe was added during the 48 h of the experiment, [3H]IR-SRIF synthesis in response to T3 by cortical cells significantly increased after exposure to 10(-11) M (P less than 0.05) and decreased with 10(-7) M (P less than 0.05). When [3H]Phe was added for only the last 3 h or incubation with T3, the action was inhibitory at both 10(-11) M and 10(-7) M. Trichloroacetic acid precipitable material decreased in a dose response manner between T3, 10(-11) M and 10(-7) M. These findings suggest that at this time of brain development, SRIF synthesis by cortical and hypothalamic cells is affected by TH.
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PMID:Thyroid hormone action on biosynthesis of somatostatin by fetal rat brain cells in culture. 289 3

Primary cultures of rat thyroid cells were made in medium supplemented with 0.1--0.5% calf serum and containing six hormones or growth factors: insulin, thyrotropin, transferrin, hydrocortisone, somatostatin, and glycyl-L-histidyl-L-lysine acetate. The FRTL strain was purified by successive colonial isolations and was found to maintain highly differentiated features (secretion into the culture medium of physiological amounts of thyroglobulin and concentration of iodide by 100-fold). The FRTL strain has been observed for more than 3 years in continuous culture. It has maintained the same biochemical and morphological characteristics that typified the primary cultures of thyroid follicular cells immediately after their enzymatic release from the rat thyroid. Thyroid epithelial cells that were grown under more conventional cell culture conditions failed to retain these specialized characteristics. We show that maintenance in vitro of these specialized functions of rat thyroid follicular cells is dependent on low serum concentrations and supplementation with hormones in the primary cultures. Our observations indicate that this culture strategem may be aplicable to the general problem of maintenance of differentiated characteristics in cultures of other epithelial cells.
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PMID:Culture of hormone-dependent functional epithelial cells from rat thyroids. 610 91


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