UNIPROT:P61278 - FACTA Search

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin receptors have been demonstrated on various tumors of neuroendocrine and other origin. They have been detected in vitro by biochemical techniques as well as by autoradiography. The development of long-acting somatostatin analogs and the recent availability of radiolabeled octreotide have made the in vivo detection of somatostatin receptors possible. This preliminary study embraced 45 patients with meningiomas, brain tumors or pituitary tumors, which were imaged by planar and tomographic scintigraphy after intravenous injection of 111Indium-labeled octreotide. In all of the meningiomas studied (unifocal and multifocal tumors in various locations), a high density of somatostatin receptors was detected by scintigraphy. Pituitary tumors were slightly positive in 50% of cases only, independent of the endocrine activity. Gliomas with an intact blood-brain barrier showed no enhanced tracer uptake in vivo, while gliomas with disturbed blood-brain barrier had a high activity uptake. We conclude that in vivo somatostatin receptor scintigraphy, although not tumor-specific, may aid in the preoperative diagnosis and staging of intracranial tumors, especially skull base tumors.
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PMID:Somatostatin receptor scintigraphy in brain tumors and pituitary tumors: first experiences. 833 Aug 74

Pituitary tumours result in hypersecretion of different hormones which can be used in diagnosis. Prolactinomas can be diagnosed by measurement of prolactin serum concentration. Prolactin concentrations of > 150 to 200 micrograms/l are invariably due to macroprolactinoma. Lower levels may indicate microprolactinoma or a peripituitary tumour. Computed tomography scans visualize (micro)prolactinomas of 3 mm. Diagnosis of acromegaly is now based on measurement of serum IGF-I concentration. IGF-I levels correlate with the old test which measured insufficient suppression of GH levels to < 2 micrograms/l in response to oral glucose load. Most endocrine tumours have somatostatin receptors, allowing visualization with radiolabelled somatostatin analogues. 111In-diethylenetriaminopentaacetic acid-octreotide allows normal pituitary and somatostatin positive tumours to be visualized. A positive scan is predictive of good response to octreotide therapy. Cushing's syndrome is diagnosed by ecchymoses, myopathy, hypertension, and by measurement of the overnight 1 mg dexamethasone suppression test, urine cortisol levels and the diurnal cortisol rhythm. Clinically nonfunctioning macroadenomas in post-menopausal women often do not immunostain for gonadotropins. Serum gonadotropin levels are not elevated, although they do release gonadotropins or subunits in vitro. Diagnosis is assisted by TRH administration which increases serum gonadotropins or subunits, especially LH-beta.
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PMID:Current tools in the diagnosis of pituitary tumours. 837 8

Immunosuppressant agent FK506 has been reported to stimulate ACTH release from pituitary cells. We examined the effects of FK506 on GH release from the rat anterior pituitary cells and the effects of FK506 on hypothalamic GH- releasing hormone (GRH) and somatostatin (SS) gene expression in conscious male rats. In vitro experiments, the monolayer pituitary culture and reverse hemolytic plaque assay were employed to examine the GH release from the rat anterior pituitary cells. In in vivo experiments, the FK506 was administered for 7 days and then sequential blood sampling was performed every 20 min during 6 h in conscious rats. The hypothalamus was removed, and total RNA was extracted for Northern blot analysis. The FK506 significantly stimulated GH release from the rat anterior pituitary cells in a dose-dependent manner in vitro. In in vivo experiments, the area under the curve of GH surges was significantly increased in FK506-treated rats, although the peak height and the trough level of GH surges were not altered. Pituitary GH messenger RNA (mRNA) levels were significantly increased by the FK506 treatment. Hypothalamic GRH mRNA levels were significantly increased in FK506- treated rats, whereas hypothalamic SS mRNA levels were not altered. These findings indicate that FK506 stimulates GH secretion and gene expression of hypothalamic GRH in the rat.
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PMID:Immunosuppressant agent FK506 stimulates growth hormone (GH) secretion and gene expression of hypothalamic GH-releasing hormone in the rat. 860 82

The differential diagnosis of tumours in the skull base is often difficult. With the experience that various intracranial tumours differ in their expression of somatostatin binding sites (SBS) somatostatin receptor scintigraphy (SRS) with the somatostatin analogue octreotide can give additional information of the tumour entity. Seventy patients with various tumours of the skull base were examined with 111Indium-labelled DTPA-octreotide injected i.v.. Planar and tomographic images were obtained with a gamma camera 4-6 and 24 hours after injection. All of the meningiomas (unifocal and multifocal tumours in various locations) showed a high density of SBS whereas in none of the examined neurinomas SR were found. Pituitary adenomas revealed in only 50% SR in different concentrations and independent of the endocrine activity. SRS can help in the differential diagnosis between meningiomas and other tumours, postoperative scar or radionecrosis at the skull base. A dural infiltration with meningioma tissue ("meningeal sign") may be discriminated from a reactive hypervascularisation in lesions with a diameter > 0.5 cm. We conclude that SRS can offer additional diagnostic aspects in the pre- and postoperative management of patients with skull base tumours.
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PMID:Clinical relevance of somatostatin receptor scintigraphy in patients with skull base tumours. 873 8

Pituitary cells appear to be programmed to proliferate in response to cyclic adenosine monophosphate (cAMP), leading to tumorigenesis. Stimulatory neurohormones and inhibitory inputs normally act in opposition to control cAMP levels, but receptor/postreceptor alterations may affect their relative effects. Most growth hormone (GH), corticotropin (ACTH)-, prolactin (PRL)-, and gonadotropin-secreting adenomas and nonfunctioning pituitary adenomas (NFPA) possess specific thyrotropin-releasing hormone (TRH) receptors, normally coupled with cytosolic [Ca2+]i increase and diacyl glycerol production. These cells are also sensitive to other peptides such as vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase-activating peptide (PACAP), which activate adenylyl cyclase in many hormone-secreting adenomas and in all NFPA. The two main inhibitory agents controlling pituitary function are somatostatin (SS) and dopamine (DA), which have been reported to reduce hormone hypersecretion and tumor growth in a variable percentage of patients. Inhibition of adenylyl cyclase activity and cytosolic [Ca2-]i levels is involved in the transduction of DA signals in normal and tumoral mammotrophs, but in GH-secreting adenomas DA receptors are exclusively and defectively coupled only with [Ca2+]i reduction. The abnormal expression of these receptors can amplify stimulatory signals with both secretory and proliferative potential. The availability of specific G proteins may qualify the cell response to inhibitory agents. For example, in a subset of NFPA, SS alone or DA alone causes an abnormal increase in [Ca2+]i levels due to Ca2+ mobilization from intracellular stores.
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PMID:Cellular abnormalities in pituitary tumors. 876 79

Testosterone (T) administration to pubertal boys increases spontaneous GH secretion. It is not known whether this occurs via pituitary or hypothalamic mechanisms. We evaluated the GH secretion of 12 boys, aged 13.67 +/- 0.37 yr (mean +/- SE), diagnosed with constitutional delay in growth and adolescence. The evaluation was made both before and after 3 months of treatment with T or the nonaromatizable androgen, 5 alpha-dihydrotetosterone. Serum for determination of spontaneous GH secretion was sampled every 20 min for 24 h. Pituitary responsiveness was assessed by the administration of GHRH with sampling of GH at intervals for the next 2 h. This was also done with pyridostigmine (PDS) pretreatment to assess the effects of somatostatin. The dose of androgen used was 80 mg/m2 month. All tests were then repeated during treatment. Spontaneous GH secretion was analyzed by the Cluster method. The response to GHRH was measured as the area under the curve. Somatostatin effects were quantified as the difference in responsiveness between the two GHRH tests performed at each admission: one without prior PDS administration and one in which somatostatin was blocked by PDS. Treatment with T increased mean spontaneous GH secretion from 2.25 +/- 0.34 micrograms/L before treatment to 6.77 +/- 0.69 micrograms/L (mean +/- SE; P < 0.001) and mean spontaneous peak height from 5.62 +/- 1.05 to 17.21 +/- 1.52 micrograms/L (mean +/- SE; P < 0.001). No significant differences between pretreatment and treatment evaluations for any spontaneous GH secretory parameters were seen in 5 alpha-dihydrotestosterone-treated patients, except that maximum peak height was decreased after treatment (P < 0.02). In T treated patients, the GHRH stimulation tests without prior PDS administration changed from 84.14 +/- 34.54 total micrograms/L before to 102.3 +/- 35.82 total micrograms/L (mean +/- SE; P = NS) after androgen treatment. PDS pretreatment produced an increase in responsiveness to GHRH over the test without PDS pretreatment. This increase was 127.03 +/- 35.68 total micrograms/L before T treatment; after T treatment, this increase was 78.38 +/- 57.6 total micrograms/L (mean +/- SE; P = NS). T treatment, via an estrogen-dependent mechanism, caused increased GH pulse amplitude, thereby increasing the mean serum GH concentration. This increase was not the result of increased pituitary responsiveness or decreased somatostatin tone. This indicates that T exerted its effect on GH via increased GHRH pulse amplitude.
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PMID:The effects of testosterone and dihydrotestosterone on hypothalamic regulation of growth hormone secretion. 877 2

Many important advances in our understanding of the growth hormone (GH) axis have occurred during the last decade. A number of neurotransmitters and neuropeptides are implicated in the control of growth hormone-releasing hormone (GHRH) and somatostatin release; however, the role of many of these, such as serotonin, gamma-aminobutyric acid and dopamine, is still a matter of discussion. As a newly isolated hypothalamic peptide with a possible role in the control of GH secretion, pituitary adenylate cyclase activating peptide has received considerable attention. Synthetic hexapeptides that stimulate GH release (GH-releasing peptides 1, 2 and 6) have been identified. Pituitary-specific transcription factors involved in the expression of the GH gene have been identified, the GHRH receptor gene has been cloned, as well as a number of somatostatin receptor genes, and advances in our understanding of the insulin-like growth factor-binding proteins, and growth hormone-binding proteins have been made.
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PMID:The growth hormone axis: control and effects. 880 20

Pituitary transcription factor-1 (Pit-1 or GHF-1) is a transcription factor specific to the anterior pituitary and is involved in the expression and regulation of the growth hormone (GH), prolactin (PRL) and thyroid-stimulating hormone (TSH) beta-subunit genes. The expression of these three genes can be modulated by changes in the hormone environment and it is thought that some of these effects are mediated through Pit-1, but little is known about the physiological regulation of this transcription factor. Therefore, we first asked whether Pit-1 gene expression is modified as a result of changes in the in vivo gonadal steroid environment and if this could be correlated with changes in GH and/or PRL mRNA levels. Secondly, we sought to determine if sex steroids affect the mRNA levels of these three peptides by acting at the level of the pituitary and whether these effects are androgen or estrogen mediated. Finally, how sex steroids modulate the response of these three genes to the hypothalamic neuropeptides growth hormone-releasing hormone (GHRH) and somatostatin (SS) was analyzed. To this end, we compared Pit-1, GH and PRL mRNA levels in the anterior pituitary of intact, castrated, and castrated testosterone-replaced adult male rats. In addition, primary cultures of adult male pituitaries were used to study the direct effects of both androgens and estrogens on Pit-1, GH, and PRL mRNA levels. In situ hybridization histochemistry was used to compare relative levels of Pit-1, GH and PRL mRNA. Densitometric analysis of the in vivo studies showed that castration resulted in a 57, 40 and 55% decline in Pit-1, GH and PRL mRNA signal levels, respectively. Furthermore, replacement with testosterone (T) at the time of castration completely prevented the decline in all three mRNA species (ANOVA: Pit-1 mRNA, p < 0.0001; GH mRNA, p < 0.0001; PRL mRNA, p < 0.0001). In vivo, both T (10(-7) M) and estradiol (10(-9) M) were capable of stimulating Pit-1 mRNA and PRL mRNA levels, while dihydrotestosterone (DHT; 10(-7) M) had no effect. There was no effect of any of these steroid treatments on GH mRNA levels in vitro. Addition of GHRH to the cultures increased GH mRNA levels, as well as those of Pit-1 and PRL, and SS had the opposite effect on GH mRNA levels. Whereas the GH response to GHRH was not significantly modified by exposure to sex steroids, the effect of SS was. The presence of sex steroids was capable of modifying the Pit-1 and PRL responses to both GHRH and SS. These results clearly indicate that changes in circulating levels of sex steroids modulate the expression of Pit-1 in the anterior pituitary and that these changes can be correlated with commensurate modifications in GH and PRL mRNA levels. Furthermore, the effect on both Pit-1 and PRL mRNA levels occurs, at least in part, at the level of the anterior pituitary and is an estrogen-receptor-mediated event. In contrast, the effects of gonadal steroids on GH mRNA levels are less direct and are most likely mediated at the level of the hypothalamus, as well as through modulation of the response of the somatotroph to hypothalamic factors. We conclude that the transcription factor Pit-1 is actively regulated physiologically and may be involved in mediating some of the effects of sex steroids and hypothalamic factors on the synthesis of certain anterior pituitary hormones.
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PMID:In vivo and in vitro regulation of pituitary transcription factor-1 (Pit-1) by changes in the hormone environment. 883 50

Pituitary adenylate cyclase-activating peptide (PACAP) is a 38-amino acid polypeptide, first isolated from ovine hypothalamus, which directly stimulates the release of several pituitary hormones, including GH, ACTH, and LH. The presence of PACAP receptors in several brain areas, including the hypothalamus, suggests that this peptide might play a role as neurotransmitter/neuromodulator. We have thus investigated the effects of intracerebroventricular (i.c.v.) and intravenous (i.v.) injections of PACAP and the potent PACAP antagonist PACAP(6-38) on gonadotropin-releasing hormone (GnRH) and somatostatin (SS) gene expression in the male rat hypothalamus. The levels of mRNA were measured at the cellular level by quantitative in-situ hybridization. The i.c.v. injection of PACAP produced a 12.5% increase in the GnRH mRNA levels, an effect which was completely prevented by the concomitant administration of the PACAP antagonist. The administration of the PACAP antagonist induced by itself a 12.9% decrease in the hybridization signal. The i.v. administration of the same peptides induced modifications in GnRH gene expression which were completely opposite to those produced by i.c.v. administration. In somatostatinergic neurons located in the periventricular nucleus, the i.c.v. injection of the peptides induced modification in SS gene expression which were very similar to those observed for GnRH gene expression, although the changes were less striking. The i.v. administration of PACAP or its antagonist did not induce any change in the levels of SS mRNA. These results then strongly suggest that PACAP might be involved in a positive regulation of two neuropeptides involved in the control of anterior pituitary secretion via central specific receptors. The inverse influence of PACAP on GnRH gene expression after the i.v. injection might be explained by the short feedback effect induced by the direct stimulation of gonadotropin hormone release following the systemic injection of the peptide.
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PMID:Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on gonadotropin-releasing hormone and somatostatin gene expression in the rat brain. 888 47

This study examines the influence of fetal ethanol (ETOH) exposure and pair-feeding dams on postnatal, releasing factor-induced pituitary growth hormone (GH) release and adenosine 3',5'-cyclic phosphate (cAMP) accumulation. Fetuses were exposed to ETOH in utero by feeding dams a 36% (calories derived from ETOH: 6.6% v/v) ETOH liquid diet. Postnatal body weights were measured at sacrifice to evaluate the influence of ETOH on growth. Pituitary weight and protein content were measured to determine if changes in GH secretion or cAMP are proportional to the overall effect of ETOH on the pituitary. Pituitaries from 1-, 10-, and 60-day-old pups were explanted and incubated without hormones or with either somatostatin [somatotropin-release inhibiting factor (SRIF); 10(-9) M], or GH-releasing factor (GRF; 5 x 10(-9) M). Radioimmunoassays were used to determine tissue cAMP content, after extraction, and media GH concentration. Results indicate that fetal ETOH exposure specifically reduces the weight of both male and female pups. However, by 60 days of age, this reduction is not different from that found in pups of pair-fed controls, and both groups weighed less than pups of ad libitum controls. Furthermore, both pituitary weight and protein content were proportionately reduced in ETOH-exposed pups. In regard to releasing factor sensitivity, compared with pituitaries from ad libitum controls, the capacity of GRF to simulate GH release was diminished in 10-day-old males (p < 0.006) exposed to ETOH. On the other hand, the capacity of GRF to stimulate cAMP accumulation was generally enhanced by prenatal ETOH exposure. The capacity of SRIF to depress GH release was diminished in ETOH pups, compared with both pair-fed and ad libitum-fed controls (p < 0.0001). This difference in GH release was more apparent in pituitaries from females than males (p < 0.001). However, the depressed SRIF response was not associated with altered cAMP accumulation. These data suggest that fetal ETOH exposure has a sexually dimorphic effect on pituitary sensitivity to GH-releasing factors that may be related to altered regulation of GH release and susceptibility to growth retardation.
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PMID:Effect of fetal alcohol exposure on postnatal pituitary adenosine 3', 5'-cyclic phosphate content and growth hormone release. 890 74

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