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)

This study examined the effects of chronic deletion of circulating growth hormone-releasing (GHRH) and/or somatostatin (SRIF) on normal growing male rats, as well as the effects of exogenous GHRH (1-29)NH2 and/or SMS 201-995 administration on the growth of rats with hypothalamic ablation. Passive immunization with anti-rat GHRH goat gamma-globulin (GHRH-Ab) for 3 weeks caused a marked decrease in the levels of pituitary GH mRNA and severe growth failure. Treatment with anti-SRIF goat gamma-globulin (SRIF-Ab) for 3 weeks produced a more modest decrease in GH mRNA levels in the pituitary and a slight but significant inhibition of normal somatic growth. Hypothalamic ablation produced a marked decrease in the level of mRNA in the pituitary. Chronic continuous administration of GHRH (1-29)NH2 stimulated pituitary GH synthesis, elevated serum levels of insulin-like growth factor I and increased body weight gain in rats with hypothalamic ablation treated with replacement doses of cortisone, testosterone and L-thyroxine. Combined treatment with GHRH (1-29)NH2 and SMS 201-995 appeared to promote the effect of GHRH on pituitary GH release and somatic growth in these animals. The results suggest that continuous administration of GHRH will be useful in the treatment of children with growth retardation resulting from hypothalamic disorders. In children with combined GHRH and somatostatin deficiencies, the addition of somatostatin to a GHRH treatment regimen may produce better results.
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PMID:GHRH treatment: studies in an animal model. 256 26

Membrane receptors for D-Trp6-luteinizing hormone-releasing hormone (D-Trp6-LH-RH), somatostatin-14 (SS-14), and insulin-like growth factor I (IGF-I) were estimated in MXT mammary cancers of mice using sensitive multipoint micromethods. The receptors were characterized in untreated animals and following in vivo treatment with microcapsules of the agonist D-Trp6-LH-RH and the somatostatin analog RC-160, which strongly inhibited tumor growth. In the control group, D-Trp6-LH-RH was bound to the single class of saturable, specific, noncooperative receptor sites (Kd, = 29.3 +/- 8.48 x 10(-9) M; Bmax = 4.55 +/- 0.31 pmol/mg membrane protein). Treatment with D-Trp6-LH-RH alone or in combination with RC-160 produced down-regulation of membrane receptors for D-Trp6-LH-RH on MXT mammary tumor cells. RC-160 alone and ovariectomy were without effect on D-Trp6-LH-RH receptors. On the membrane surface of MXT mammary cells, we found one class of high affinity, specific, saturable binding sites for SS-14 (Kd = 4.4 +/- 1.9 x 10(-9) M; Bmax = 0.58 +/- 0.21 pmol/mg membrane protein). Treatment with RC-160 alone or combined with D-Trp6-LH-RH significantly increased both the dissociation binding constant (Kd = 18.6 +/- 3.5 x 10(-9) and 10.1 +/- 0.7 x 10(-9) M, respectively) and the binding capacity (Bmax = 13.98 +/- 1.7 and 21.00 +/- 4.0 pmol/mg membrane protein, respectively). We also found specific binding sites (Kd = 3.01 +/- 0.15 x 10(-9) M; Bmax = 2.24 +/- 0.96 pmol/mg membrane protein) for IGF-I in the membrane fractions of MXT mammary cancers. Chronic treatment with D-Trp6-LH-RH and RC-160 alone or in combination, as well as ovariectomy, significantly decreased the dissociation binding constant of IGF-I membrane receptors on MXT mammary cells. Our results strongly suggest an important role of LH-RH, SS-14, and IGF-I in the growth of MXT mammary carcinoma. Changes in characteristics of receptors after treatment with analogs of LH-RH and SS-14 along with tumor growth inhibition provide additional support for the direct effect of these peptides on tumor cells. A possible significance of these findings as applied to a clinical environment is discussed.
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PMID:Receptors for D-Trp6-luteinizing hormone-releasing hormone, somatostatin, and insulin-like growth factor I in MXT mouse mammary carcinoma. 257 66

The parafollicular-cell (C-cell) hormone calcitonin (CT) can preserve or even augment skeletal mass by inhibiting osteoclast-mediated bone resorption. The possibility of an additional anabolic skeletal influence has also been raised: C cells might, via CT or other secretory products, affect osteoblast-mediated bone formation. The 57-residue amino-terminal procalcitonin cleavage peptide, N-proCT, has recently been identified in human and rat C cells, where it is made and secreted in equimolar amounts with CT. The coelaboration of N-proCT and CT and N-proCT's sequence conservation during evolution prompted us to investigate the potential skeletal bioactivity of N-proCT. We found that synthetic human N-proCT, at nanomolar concentrations, stimulated proliferation of normal and neoplastic human osteoblasts. At maximally effective doses, human N-proCT caused more than a 100% increase above the control rate of DNA synthesis, an effect comparable to the maximal growth effect of insulin, a potent mitogen for osteoblasts. Human N-proCT exerted a similar maximal mitogenic effect in chicken osteoblast cultures but at 1000-fold greater concentrations than in human bone-cell cultures. The bone-cell action of N-proCT was potentiated with insulin with a greater than 200% increase in DNA synthesis at high insulin concentrations. In sharp contrast to these findings for N-proCT, the other bioactive C-cell peptides, CT and somatostatin, showed no mitogenic effects in human or chicken osteoblast cultures. Our results indicate that the action of N-proCT on cultured bone cells is separate from and potentiated by insulin, a known growth factor. Unlike insulin and related growth factors such as insulin-like growth factor I, N-proCT is not mitogenic in skin fibroblast cultures. We propose that N-proCT is a C-cell hormone that promotes bone formation via stimulatory actions on osteoblasts and preosteoblasts.
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PMID:Procalcitonin's amino-terminal cleavage peptide is a bone-cell mitogen. 259 82

There have now been many studies on the effects of growth hormone (GH) on renal function. Chronically elevated GH levels, such as occur in acromegaly, are associated with an increase in renal plasma flow (RPF), glomerular filtration rate (GFR) and kidney size. When GH falls in these individuals (such as, after hypophysectomy in acromegalic patients), RPF, GFR and renal size decrease. A rapid increase in plasma GH in normal or growth hormone deficient adults, such as occurs after GH injection, causes an increase in RPF and GFR. However, these effects on renal function are delayed, occurring between 5.5 and 23 hours after the GH injection and in association with an elevation in the plasma concentrations of insulin-like growth factor I (IGF-I). These observations suggest that IGF-I may mediate the GH stimulated increase in RPF and GFR. We evaluated this question in rats starved for three days. A 20 minute infusion of IGF-I causes an increase in RPF and GFR in these animals. This effect could be blocked by indomethacin but not by somatostatin. These findings suggest that: 1) GH injection does increase RPF and GFR; 2) this effect on GH, which is delayed for several hours seems to be mediated by IGF-I; and 3) a 20-minute IGF-I infusion itself increases RPF and GFR in starved rats. The effect of IGF-I on renal function seems to require the presence of eicosanoids. Further studies will be necessary to examine whether IGF-I is a physiological regulator of renal function.
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PMID:Effects of growth hormone and IGF-I on renal function. 263 57

Tumors of several organs have been shown to bear cell surface receptors for insulin-like growth factor I (IGF-I), and to exhibit dependence on this mitogen for optimum proliferation both in vivo and in vitro. To investigate the feasibility of a novel form of endocrine therapy that would exploit such dependence, we treated 8 patients with non-endocrine solid tumours with the somatostatin analogue SMS 201-995, in an effort to reduce growth hormone-stimulated IGF-I production. Significant decreases in basal and arginine-stimulated serum growth hormone and serum IGF-I were noted. This approach deserves evaluation as a potentially useful form of palliative endocrine therapy for certain cancers.
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PMID:Somatostatin analogue SMS 201-995 reduces serum IGF-I levels in patients with neoplasms potentially dependent on IGF-I. 281 14

The influence of cyclic 3',5'-guanosine monophosphate (cGMP) on the lipolytic and antilipolytic (inhibition of glucagon-stimulated lipolysis) responses to GH (1 microgram/ml) was examined in chicken adipose tissue in vitro. Both 8-bromo-cGMP (0.1 mM) and sodium nitroprusside (1 mM) (a guanyl cyclase stimulator) completely inhibited the lipolytic effect of GH. A cGMP-lowering agent, LY83583 (10 microM), reversed the inhibitory effect of sodium nitroprusside on GH-stimulated lipolysis. Furthermore, the suppressive effects of insulin (100 ng/ml), insulin-like growth factor I (IGF-I) (100 ng/ml), or insulin-like growth factor II (IGF-II/MSA) (100 ng/ml), but not somatostatin (1 ng/ml), on GH-stimulated lipolysis were prevented by LY83583 addition. Neither 8-bromo-cGMP, sodium nitroprusside, nor LY83583 altered GH-induced inhibition of glucagon (1 ng/ml)-stimulated lipolysis. It is proposed that cGMP may mediate inhibitory control of GH-stimulated lipolysis by insulin, IGF-I, and IGF-II in chicken adipose tissue.
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PMID:Inhibition of growth hormone-induced lipolysis by 3',5'-guanosine monophosphate in chicken adipose tissue in vitro. 284 72

The effect of immunizing against somatostatin (SRIF), with SRIF conjugated to bovine thyroglobulin, was examined in cross-bred sheep fed either cut pasture or lucerne pellets. Plasma concentrations of GH were unaffected by SRIF immunization, but were lower in pellet-fed sheep. Plasma concentrations of insulin-like growth factor I (IGF-I) increased after immunization in sheep on both diets. Pasture-fed sheep had lower plasma concentrations of IGF-I than those on pellets. Sheep showed a small increase in growth rate in response to immunization. Immunization had no effect on carcass composition and did not affect plasma concentrations of IGF-II, free fatty acids or glucose. The results show that even though SRIF immunization increases plasma concentrations of IGF-I, it does not necessarily result in a large increase in growth rate.
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PMID:Effect of nutrition and immunization against somatostatin on growth and insulin-like growth factors in sheep. 288 Sep 20

It is generally accepted that hypothalamic somatostatin and hepatic insulin-like growth factor I (IGF-I)/somatomedin-C act directly on the pituitary to inhibit GH release, but it is not known whether all somatotropes are responsive to these agents. In the present study, we used a reverse hemolytic plaque assay to compare the acute (8 h) effects of somatostatin and IGF-I on the release of GH from individual cells in 24-h cultures of male rat pituitaries. Treatment with these factors caused comparable dose-dependent decreases in both the rate of plaque formation and the percentage of cells which released GH. In 8-h incubations, maximal (10(-8) M) doses of IGF-I or somatostatin alone decreased the percentage of GH-releasing cells to approximately the same degree (from 34.4% in controls to 29.7% and 28.4%, respectively), yet the effects of these factors were additive when both agents were applied to the same cells (to 24.5%). When we analyzed the sizes of plaques (an index of the amount of hormone released per cell) which resulted from these treatments, we noted that somatostatin was a much greater suppressor (to 11% of control value) of GH release than IGF-I (60% of controls). Coincubation with 10(-8) M GH-releasing factor had no effect on the percentage of GH-releasing cells at 8 h but completely overrode the inhibitory effect of IGF-I on plaque size without affecting the somatostatin-induced decrease in this regard. Taken together, these data suggest that IGF-I and somatostatin act, at least in part, on separate subpopulations of rat somatotropes. Somatostatin is a much more effective inhibitor of total GH release than IGF-I and appears to affect most, if not all, somatotropes. In contrast, IGF-I acutely inhibits GH release (prevents plaque formation) from some somatotropes, but does not seem to affect the remaining GH cells.
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PMID:Existence of somatotrope subpopulations which are differentially responsive to insulin-like growth factor I and somatostatin. 288 99

Using a monolayer approach, we have examined the acute (3 h) effects of GRF, somatostatin (SRIF), and insulin-like growth factor I (IGF-I) on GH release from pituitary cells of male and female 70-, 100-, and 130-day-old fetuses and newborn lambs and of prepubertal male lambs. GRF stimulated basal GH release in a dose-dependent (10(-12)-10(-8) M) manner at each stage in development. There was no linear relationship between maximal response and increasing age of the donor animals. The ED50 values for GRF were similar in all groups, except in the pituitaries from male and female 130-day-old fetuses, where the ED50 values were significantly higher. SRIF elicited a dose-related (10(-10)-10(-6) M) inhibition of basal GH secretion at each stage of fetal life and in the prepubertal period; although the response was lower in the youngest fetal pituitaries, there was no significant change in maximal response during the fetal or prepubertal period. No effect of SRIF on basal GH secretion was observed in newborn lambs. However, SRIF (10(-7) M) was able to block GRF (10(-8) M)-stimulated GH release in 100- and 130-day-old fetal and prepubertal as well as newborn lamb pituitary cells. Plasma IGF-I concentrations increased from 15.0 +/- 0.7 (mean +/- SE) and 13.8 +/- 0.9 ng/ml for male and female animals, respectively, at 70 days gestation to 55.8 +/- 3.2 and 51.8 +/- 11.1 ng/ml at the time of birth. The increase was much more pronounced in prepubertal lambs, especially in male animals, where IGF-I levels reached 300.8 +/- 37.7 ng/ml. IGF-I (100 ng/ml) had no effect on basal GH release in 70- and 100-day-old fetal, newborn, and prepubertal lamb pituitary cultures, but significantly inhibited basal GH secretion from 130-day-old fetal cells. This dose of IGF-I had no effect on GRF (10(-9) M)-stimulated GH release at 70 days gestation. It significantly inhibited this effect at 100 days and in prepubertal lamb cells. In 130-day-old fetal and newborn lamb pituitary cultures, IGF-I completely blocked the GH response to GRF.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vitro regulation of growth hormone (GH) release from ovine pituitary cells during fetal and neonatal development: effects of GH-releasing factor, somatostatin, and insulin-like growth factor I. 289 19

TPA (12-O-tetradecanoylphorbol 13-acetate) is one of a class of compounds known as tumor promoters which perturb the inositol phosphate pathway in a number of cells. We have used TPA in a dispersed rat adenohypophysial cell system to probe the characteristics of growth hormone (GH) release. In this system we have found that the cells release GH in response to low concentrations of TPA: the EC50 was 0.23 +/- 0.05 nM (n = 6) and the maximal concentration was 5 nM. However, the maximal TPA-induced GH release was only 34 +/- 5% (n = 7) of the GH released by maximal growth hormone releasing factor (GRF) suggesting TPA releases a subpool of stored GH. Both somatostatin and insulin-like growth factor I inhibit GH release stimulated by TPA to the same extent as that stimulated by GRF, showing that the normal inhibitory control mechanism of release is not altered. Incubation in a low calcium medium that totally blocks GRF-stimulated GH release also inhibits TPA-stimulated GH release. The calcium channel blockers nifedipine and diltiazem both partly inhibit GRF- and TPA-stimulated GH release, showing some component of the calcium necessary for GH release arises from influx across the cell membrane.
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PMID:Characteristics of phorbol ester stimulated growth hormone release: inhibition by insulin-like growth factor I, somatostatin, and low calcium medium and comparison with growth hormone releasing factor. 289 38


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