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

The tissue-specific expression of a fusion gene encoding the mouse metallothionein-1 promoter and the coding region of the human GH-releasing hormone (hGRH) gene was studied in transgenic mice by immunohistochemistry using an anti-hGRH serum that does not recognize endogenous mouse GRH. hGRH immunoreactivity (GRH-IR) was detected in specific cells of the pituitary, pancreas, kidney, duodenum, lung, testis, ovary, adrenal, heart, and brain. In the pituitary, using double immunofluorescent staining, GRH-IR was found in some, but not all, somatotrophs, gonadotrophs, thyrotrophs, and mammotrophs. GRH-IR was found in both pancreatic exocrine cells and endocrine islets. Within the islet, GRH-IR was colocalized in A and D cells with glucagon and somatostatin, respectively. Immunopositive cells in other tissues were localized in kidney proximal convoluted tubules, duodenal submucosal glands of Brunner, the smooth muscles of pulmonary arterioles, testicular Leydig cells, oocytes, adrenal medullary chromaffin cells, and cardiac atria. In the brain, GRH-IR was seen in the external layer of the median eminence and in perikarya and fibers of the hypothalamic arcuate nucleus, the parvocellular region of the paraventricular nucleus, the supraoptic nucleus, and the amygdala. Somatostatin-immunoreactive cell bodies and fibers in transgenic and control mouse hypothalamus were not appreciably different. In summary, hGRH expression in transgenic mice occurs in a cell-specific manner in the hypothalamus as well as in numerous other tissues, many of which have secretory functions.
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PMID:Immunohistochemical analysis of human growth hormone-releasing hormone gene expression in transgenic mice. 250 76

Insulin-like growth factor I (IGF-I) suppresses GH gene transcription and GH secretion, while somatostatin (SRIF) only suppresses GH secretion. The interaction of these inhibitors of GH was, therefore, tested in primary rat pituitary cells grown in serum-free medium. Maximal inhibition of GH secretion (to 30% of the control value) was achieved by 13 nM IGF-I, while 5 nM SRIF suppressed GH to 36% of control secretion. The respective ED50 values for IGF-I and SRIF inhibition of GH secretion were similar (approximately 2.5 nM). Treatment of cells with the two agents together resulted in a further inhibition of basal GH secretion to 18% of control untreated cells (P less than 0.005). Increasing doses of SRIF (2.5-10 nM) in the presence of IGF-I caused a dose-dependent suppression of GH secretion. PRL levels were not altered by these treatments, indicating a selective effect on GH. GRH-induced GH secretion was further attenuated by combined IGF-I and SRIF treatment compared to the effect of either of these two agents alone. Northern analysis showed that IGF-I suppressed GH mRNA transcripts, while SRIF did not alter GH mRNA levels. The results indicate that physiological concentrations of both IGF-I and SRIF suppress long term basal GH secretion. Only IGF-I alters GH mRNA levels. These two peptides, therefore, appear to attenuate in vitro GH secretion by different mechanisms.
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PMID:Insulin-like growth factor-I action on growth hormone secretion and messenger ribonucleic acid levels: interaction with somatostatin. 256 39

Growing male lambs were fed with diets containing 14.0, 10.8 and 7.6% protein for 3 months to determine their effects on the content of hypothalamic LHRH and SRIH and pituitary LH and GH, using immunohistochemical methods. Lowering the concentration of dietary proteins caused marked changes in the immunoreactivity of these hormones. The immunoreactive (IR) content of LHRH stored in the median eminence was enhanced, and the proportion of LH cells and their IR content increased. Opposite effects were observed in the SRIH/GH system; IR SRIH content stored in the median eminence markedly diminished, and, although hyperplasia of GH cells was observed, their IR content was diminished. This study indicates that prolonged restrictions of protein in the diet of growing male sheep affects the immunoreactive content of the investigated hormones. It seems that they suppress LHRH/LH release and augment GH release, possibly via suppression of hypothalamic somatostatin.
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PMID:Effect of protein deficiency on some hypothalamic and pituitary hormones in growing male lambs. An immunohistochemical study. 257 42

As a first step to investigate whether gonadotropin releasing hormone (GnRH) analogs might be able to modulate directly the proliferation of human epithelial ovarian carcinomata, we checked if binding sites for GnRH are present in these malignancies. Specific binding of [125I][D-Ala6-des Gly10]-GnRH-ethylamide (GnRH agonist = GnRH-A) could be demonstrated in plasma membranes from 32 out of 40 ovarian carcinomata tested. This binding was dependent on temperature, time and plasma membrane concentration. Mathematical analysis of the binding data showed that the interaction of GnRH-A with the binding sites was consistent with a single class of low affinity, high capacity binding sites (Ka = 1.42 +/- 0.14 X 10(5) M-1; range: 0.3-3.8 X 10(5) M-1; R = 209 +/- 69 X 10(-12) M/mg membrane protein; range 16-400 X 10(-12) M/mg MP; means +/- S.E., n = 32). Native GnRH and the GnRH antagonist [D-p-Glu1, D-Phe2, D-Trp3,6]-GnRH had Ka values comparable to those of the GnRH-A used. [125I]GnRH-A binding could not be displaced by oxytocin, thyrotropin releasing hormone and corticotropin releasing factor in concentrations up to 10(-4) M. Somatostatin cross-reacted with binding sites from some carcinomata, while it did not displace GnRH-A binding in membranes from others. Though the functional role of this specific binding site for GnRH in human epithelial ovarian carcinomata is still obscure, it might be part of an autocrine regulatory system and provide a possible point of attack for therapeutic approaches using GnRH analogs in this malignancy.
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PMID:Gonadotropin releasing hormone binding sites in human epithelial ovarian carcinomata. 264 75

Six normal and 8 neoplastic adrenal medullae were assayed for several immunoreactive (IR) proopiomelanocortin (POMC) and hypothalamic peptides. IR-POMC peptides were found in normal and tumor tissue in concentrations ranging from 0.0003 to 0.1% of those in pituitary. Their molecular sizes resembled those of pituitary intermediate lobe POMC peptides. No intact POMC was found. One pheochromocytoma contained fully bioactive IR-adrenocorticotropic hormone (IR-ACTH; Mr approximately 4,500) and an intermediate-sized (Mr approximately 10,000) IR-ACTH with approximately 69% bioactivity. Normal and tumorous medullae contained IR-corticotropin-releasing hormone (CRH) in concentrations ranging from 0.6 to 4% of those in hypothalamus except for one pheochromocytoma that contained 40 times that amount of IR-CRH, which was chromatographically indistinguishable from hypothalamic CRH and fully bioactive. IR-somatostatin and IR-growth hormone-releasing hormone were found in both tissue types, but IR-gonadotropin-releasing hormone and IR-thyrotropin-releasing hormone (TRH) were not, although IR-histidyl-proline diketopiperazine, a putative TRH metabolite, was found. IR-arginine vasopressin was found in two normal medullae, but not in pheochromocytomas.
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PMID:Pituitary and hypothalamic hormones in normal and neoplastic adrenal medullae: biologically active corticotropin-releasing hormone and corticotropin. 282 21

The histology, histochemistry, and ultrastructure of 43 VIP-producing tumors (34 from the pancreas, one jejunal, six retroperitoneal and two mediastinic), 37 of which were associated with the WDHA syndrome, have been investigated on paraffin sections of primary or metastatic tumor tissue. The pancreatic and jejunal tumors showed all structural and secretory patterns of epithelial endocrine tumors, including expression of cytokeratin, neuroendocrine markers like neuron-specific enolase, chromogranins and synaptophysin, peptides like VIP, PHM, GRH, PP, insulin, neurotensin, glucagon, somatostatin and enkephalin, secretory granules, small clear vesicles, peculiar osmiophilic bodies, and occasional formation of tubules or microacini with specialized luminal surfaces. All the remaining tumors were neurogenic, showing either neurons and nerve fibers together with Schwann cells (ganglioneuromas and ganglioneuroblastomas) or endocrine cells (pheochromocytomas) reacting with VIP, PHM, NPY, enkephalin, somatostatin, neuron-specific enolase, synaptophysin, and MAP2 (but not cytokeratin, PP, or GRH) antibodies. A possible origin of pancreatic VIPomas from transformed pancreatic PP cells or ductular stem cells partially committed to differentiation along the PP cell line is suggested.
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PMID:The morphology and neuroendocrine profile of pancreatic epithelial VIPomas and extrapancreatic, VIP-producing, neurogenic tumors. 283 87

Prolactin release-inhibiting factor (PIF) extracted from 1200 sheep stalk-median eminences was purified by gel filtration on a Sephadex G-25 column (4.5 X 150 cm). PIF activity was determined by measuring the inhibition of prolactin release from dispersed anterior pituitary cells of adult male or estrogen-primed, ovariectomized rats. Using this system, PIF was detected in tube fractions 122-127 (volume = 20 ml/tube). These fractions also contained LHRH and somatostatin; however, these peptides had no prolactin-inhibiting activity in the quantities present. No dopamine or gamma-aminobutyric acid (GABA) was detected in the active fractions by radioenzymatic assay and fluorophotoenzymatic assay, respectively. Furthermore, receptor blockers for dopamine or GABA did not interfere with the PIF activity. These findings indicate that the PIF activity cannot be attributed to either dopamine or GABA, both of which are known to inhibit prolactin release, and provide evidence for the presence of a non-dopaminergic and non-GABAergic PIF within the hypothalamus.
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PMID:Purification of a non-dopaminergic and non-GABAergic prolactin release-inhibiting factor (PIF) in sheep stalk-median eminence. 285 51

[125I-Tyr]Somatostatin [( 125I-Tyr]SRIH) binding was found in 11 GH-secreting pituitary adenomas [Kd = 0.46 +/- 0.15 (+/- SE) nM; maximum binding, 165 +/- 35 fmol/mg protein). This binding was specific, since it was displaced by somatostatin-14 (SRIH-14), N-Tyr-SRIH-14, and SRIH-28. In contrast, a number of peptides and drugs not structurally related to SRIH, such as bombesin, dopamine, LHRH, met-enkephalin, naloxone, neurotensin, secretin, substance P, TRH, or vasoactive intestinal peptide, did not affect [125I-Tyr]SRIH binding. [125I-Tyr]SRIH specific binding also was found in PRL-secreting pituitary adenomas. The kinetic characteristics of the specific binding were similar to those of GH-secreting adenomas. However, maximal binding was one quarter that of GH-secreting adenomas (37 +/- 9 fmol/mg protein). In contrast, nonsecreting (chromophobe) tumors were devoid of any specific binding. Finally, in acromegaly, the density of [125I-Tyr]SRIH-binding sites in the adenomas was negatively correlated with plasma GH levels before surgery (r = -0.80). This suggests that somatostatinergic control is involved in GH secretion in acromegalic patients.
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PMID:Somatostatin receptors in human growth hormone and prolactin-secreting pituitary adenomas. 286 Jan 20

Growth hormone (GH) secretory patterns were studied in a patient with ectopic growth hormone releasing factor (GRF) secretion and in normal men given continuous infusions of human growth hormone releasing factor (1-40)-OH (hGRF-40). In the patient with ectopic GRF secretion, GH secretion was pulsatile despite continuously elevated immunoreactive GRF levels. To determine if pulsatile GH secretion is maintained in normal subjects, we administered to six healthy young men vehicle or hGRF-40, 2 ng/kg per min, for 24 h and gave a supramaximal intravenous bolus dose of hGRF-40, 3.3 micrograms/kg, after 23.5 h of infusion. hGRF-40 infusion resulted in greater GH secretion than did vehicle infusion and pulsatile GH secretion was maintained throughout hGRF-40 infusion. During the 23.5 h of vehicle infusion, total GH secretion (microgram; mean +/- SEM) was 634 +/- 151 compared with 1,576 +/- 284 during hGRF-40 infusion (P = 0.042). The GH response to the intravenous bolus of hGRF-40 was greater after vehicle infusion than after hGRF-40 infusion; 877 +/- 170 and 386 +/- 125 micrograms of GH was secreted after the bolus on vehicle and hGRF-40 days, respectively (P = 0.015). The total amount of GH secreted during the 25.5 h of the two study days was not different; 1,504 +/- 260 and 1,952 +/- 383 micrograms were secreted during vehicle and hGRF-40 days, respectively (P = 0.36). Not only was pulsatile GH secretion maintained during hGRF-40 infusion, but there was augmentation of naturally occurring GH pulses, which is in contrast to the effect of gonadotropin-releasing hormone on gonadotropin secretion. We suggest that GH pulses are a result of GRF secretion that is associated with a diminution or withdrawal of somatostatin secretion.
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PMID:Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion. 286 Jan 26

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.
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PMID:Specific somatostatin receptors on human pituitary adenoma cell membranes. 286 81


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