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)

We measured plasma insulin-like growth factor I/somatomedin-C (IGF-I/SmC) concentrations and mean 24-h GH secretion serially before and during therapy with the long-acting somatostatin analog SMS 201-995 in 21 patients with acromegaly. When mean plasma GH was elevated above 12.0 +/- 0.6 (+/- SE) micrograms/L, plasma IGF-I/SmC concentrations were uniformly high, but a decline of mean plasma GH below this value was accompanied by a linear decrease in IGF-I/SmC concentrations (r = 0.89; P less than 0.001). Even mildly abnormal mean GH concentrations (greater than 4.6 but less than 10 micrograms/L) were accompanied by high plasma IGF-I/SmC values. The log dose-response interrelation between mean 24-h plasma GH and IGF-I/SmC concentrations was linear (r = 0.86; P less than 0.001). We conclude that 1) an excellent log dose-response correlation between mean 24-h plasma GH and IGF-I/SmC concentrations is present in patients with acromegaly; 2) normalization of plasma IGF-I/SmC occurs only in patients with mean daily GH output within the normal range; and 3) determination of plasma IGF-I/SmC is an accurate indicator of normalcy of GH secretion and should be used in the diagnosis of active acromegaly as well as in monitoring the progress of therapy.
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PMID:Plasma insulin-like growth factor-I/somatomedin-C in acromegaly: correlation with the degree of growth hormone hypersecretion. 289 74

A 59-yr-old woman with a disseminated carcinoid tumor was evaluated for acromegaly. She had previously undergone a hypophysectomy for acromegaly and an enlarged pituitary, with a reduction in her serum GH levels from 100 to 4 micrograms/L. Recurrence of acromegalic symptoms 2 yr later was accompanied by elevated serum GH (16 micrograms/L) and insulin-like growth factor I (IGF-I; 528 micrograms/L) and plasma GHRH levels (12 micrograms/L; normal, less than 30 ng/L). Computed tomographic scan did not reveal pituitary enlargement. Metastatic carcinoid tissue in bone removed at biopsy contained GHRH (100 pg/mg tissue). High performance liquid chromatography of plasma GHRH revealed predominantly GHRH-(3-40)-OH, a biologically inactive GHRH metabolite, along with mature GHRH forms, while carcinoid tissue contained both GHRH-(1-40)-OH and GHRH-(1-44)-NH2. Treatment with pergolide initially resulted in reduction in serum GH and IGF-I levels and amelioration of symptoms of acromegaly. However, after 14 months of pergolide therapy, serum GH levels increased despite administration of up to 1000 micrograms pergolide/day. Plasma GHRH levels remained elevated throughout the treatment period. Subsequent treatment with SMS 201-995, a long-acting somatostatin analog, for over 1 yr resulted in sustained reductions of ectopic GHRH secretion, GH hypersecretion, and IGF-I levels. Plasma GHRH levels correlated with simultaneously measured serum GH levels in response to acute SMS 201-995 administration. SMS 201-995 was an effective medical treatment for acromegaly caused by ectopic GHRH production in this patient.
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PMID:Medical management of acromegaly due to ectopic production of growth hormone-releasing hormone by a carcinoid tumor. 289 89

Ten patients with previously untreated acromegaly and invasive pituitary macroadenomas were treated with the long-acting somatostatin analog SMS 201-995 (Sandoz) for 3-30 weeks before transsphenoidal or subfrontal pituitary adenomectomy. Preoperatively, treatment with SMS 201-995 reduced mean 24-h plasma GH concentrations from 8.5-66.7 to below 4.6 micrograms/L in eight patients and by 60-80% in the remaining two patients. Pituitary tumor size decreased 20-54%. Morphologically, the tumors showed decreased total cell, cytoplasmic, and nuclear areas; varying degrees of perivascular fibrosis; and dense granularity. Postoperatively, plasma GH and insulin-like growth factor I concentrations fell into the normal range, and GH dynamics became normal in eight patients. In the remaining two patients mild GH hypersecretion persisted after surgery (mean fasting and random plasma GH, 6.1 and 7.9 micrograms/L), and in one of them GH secretion became normal 1 yr after pituitary irradiation. Thus, preoperative administration of SMS 201-995 consistently induced shrinkage of GH-producing pituitary tumors, and the apparent remission rate was high in the treated patients.
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PMID:Preoperative treatment of acromegaly with long-acting somatostatin analog SMS 201-995: shrinkage of invasive pituitary macroadenomas and improved surgical remission rate. 290 68

Somatostatin (SRIH) sensitivity in acromegaly was evaluated in vivo by comparing the inhibition of GHRH (1 microgram/kg, iv)-stimulated GH secretion in eight acromegalic and six normal subjects. A SRIH infusion (50 micrograms/h) that inhibited the mean plasma GH response to GHRH by 74 +/- 5% (+/- SE) in normal subjects had no significant effect in the acromegalic patients. However, when two acromegalic patients in whom SRIH had no suppressive effect were excluded from the analysis, the effect of SRIH in the other six (82 +/- 7%) was comparable to that in the normal subjects. Within the acromegalic group, the percent suppression of basal and GHRH-stimulated GH secretion was inversely correlated with both basal plasma GH (r = -0.751; P = 0.03 and r = -0.727; P = 0.04, respectively) and insulin-like growth factor I (r = -0.800; P = 0.02 and r = -0.727; P = 0.04, respectively) concentrations. The in vitro sensitivity to SRIH was studied in pituitary adenomas from five of the acromegalic patients in 3- to 4-day monolayer cultures of dispersed cells. The SRIH IC50 values were lowest in the tumors (8.6-44 pmol/L) from the three patients who had in vivo SRIH sensitivity (suppression of GHRH-stimulated GH secretion) comparable to that in the normal subjects. The IC50 values were higher in the tumors (150 and 21,000 pmol/L) from the two patients that were least responsive to SRIH in vivo. These results indicate that there is considerable variability of SRIH sensitivity in patients with acromegaly. Although the role of this defect in the pathogenesis of acromegaly is uncertain, it may be an important determinant in the degree of elevation of plasma GH levels.
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PMID:Comparison of the sensitivity of growth hormone secretion to somatostatin in vivo and in vitro in acromegaly. 290 71

The effects of somatostatin, insulin, insulin-like growth factor I (IGF-I), and insulin-like growth factor II (IGF-II)/MSA on growth hormone (GH) (1 microgram/ml)-induced lipolysis were examined employing chicken adipose tissue in vitro. Basal and GH-stimulated glycerol release were inhibited by somatostatin (1 ng/ml) and by IGF-II/MSA (10 and 100 ng/ml). Insulin and IGF-I (10 and 100 ng/ml) completely inhibited the lipolytic response to GH without affecting basal glycerol release. Insulin and IGF-I were equipotent in inhibiting GH-induced lipolysis while IGF-II is only 16% as potent as insulin.
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PMID:Inhibition of growth hormone-stimulated lipolysis by somatostatin, insulin, and insulin-like growth factors (somatomedins) in vitro. 290 62

The effects of somatostatin immunoneutralization on growth rate, growth hormone (GH) secretion and circulating insulin-like growth factor I (IGF-I) concentrations were investigated in chickens through the use of passive and active immunization techniques. Intravenous bolus injection of goat-antisomatostatin stimulated a significant (P less than .05) increase in plasma GH levels for one hour post-injection in four and six week old male broiler chickens. The GH response to an intravenous bolus injection of hGRF44NH2 was similar in the antisomatostatin treated chicks and normal goat serum treated controls. Despite the presence of circulating somatostatin antisera after 28 hours, plasma GH levels were not different between control and antisomatostatin-treated chicks at that time. Continuous administration of somatostatin antisera by Alzet pump over a two-week period resulted in significant (P less than .05) elevations in plasma GH levels at one week post-implantation and in circulating IGF-I concentrations after two weeks of administration. Chicks which developed antibodies against somatostatin following active immunization exhibited a 7.1% increase in growth rate which was associated with a significant decrease in abdominal fat. However, neither GH nor IGF-I concentrations were elevated in the chicks which developed somatostatin antibodies. Thus, the benefits gained from somatostatin immunoneutralization may be exerted through mechanisms other than GH.
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PMID:Effects of somatostatin immunoneutralization on growth and endocrine parameters in chickens. 290 10

The mechanisms whereby growth hormone may increase renal plasma flow (RPF) and GFR are not known, but circumstantial evidence has implicated insulin-like growth factor I (IGF-I) as a mediator of this effect. This study examined whether an infusion of IGF-I will increase RPF and GFR, whether this effect occurs quickly, and if this effect is dependent on eicosanoids or peptide hormones known to affect renal function. Rats fasted for 3 d to reduce IGF-I and IGF-I plasma binding proteins were anesthetized; then the rats received an intravenous injection of 25 micrograms/kg IGF-I, and an infusion of 25 micrograms/kg IGF-I within 20 min. Controls received infusion of the vehicle. RPF (para-aminohippurate clearances), GFR (inulin clearances), renal vascular resistance (RVR), mean arterial blood pressure (MABP), plasma IGF-I, and glucose concentrations were measured repeatedly. At the end of the 20-min infusion, plasma IGF-I tended to be increased in the animals that received IGF-I (P = 0.069), but did not increase in the control rats. IGF-I induced a significant and sustained fall in RVR and rise in RPF and GFR without any change in MABP. A small, transient, but significant decrease in plasma glucose concentrations was observed during IGF-I but not during vehicle infusion. Indomethacin, but not somatostatin, blocked the renal response to IGF-I infusion. Thus, IGF-I infusion increases RPF and GFR and reduces RVR in fasted rats. This effect requires the presence of eicosanoids but does not seem to require other peptide hormones suppressed by somatostatin.
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PMID:Evidence that insulin-like growth factor I increases renal plasma flow and glomerular filtration rate in fasted rats. 291 Sep 16

High affinity binding sites for 125I-labeled [Thr59]insulin-like growth factor I (IGF-I) were measured in rat median eminence by in vitro autoradiography with slide-mounted sections of frozen rat brain. Specific binding of 0.1 nM iodo-[Thr59]IGF-I to brain slices reached maximum by 12 h at 4 C and was unchanged at 24 h. Densitometry by computer digital image analysis of autoradiographic images indicated that specific binding of iodo-[Thr59]IGF-I to the median eminence was reversible. The specificity of binding was evaluated with competition of iodo-[Thr59]IGF-I with unlabeled [Thr59]IGF-I, rat IGF-II (multiplication-stimulating activity), and porcine insulin. All were recognized by the binding site, but the rank order of potency was [Thr59]IGF-I greater than IGF-II greater than insulin. Somatostatin was completely ineffective. Further, an antibody against the rat IGF-II receptor did not block binding of iodo-[Thr59]IGF-I to the median eminence. Fourteen days of food restriction (75% of food intake of controls) resulted in significant weight loss and reduction of plasma immunoreactive IGF-I in six food-restricted rats (0.9 +/- 0.1 U/ml) compared with values in six controls (2.6 +/- 0.5 U/ml; P less than 0.001). Binding of 125I-labeled [Thr59]IGF-I in the median eminence was significantly increased in the food-restricted rats, primarily due to an increase in the concentration of iodo-[Thr59]IGF-I-binding sites in the median eminence; the affinity (Kd) of binding was unchanged. The results indicate that the median eminence has type I IGF-I receptors, which become more numerous under metabolic conditions associated with decreased caloric intake and lowered plasma IGF-I levels.
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PMID:Characterization of insulin-like growth factor I receptors in the median eminence of the brain and their modulation by food restriction. 296 61

Effects of regulatory molecules on growth of mouse pancreatic acinar cells in culture were examined. The cholecystokinin (CCK) analogue caerulein and cholecystokinin octapeptide (CCK-8) each led to threefold increases in incorporation of [3H]thymidine into DNA. Gastrin, which interacts weakly with the CCK receptor, stimulated DNA synthesis, but only at much higher concentrations. In contrast, other secretagogues that utilize Ca2+ as an intracellular messenger, including carbachol, bombesin, substance P, and the ionophore A23187, did not induce trophic responses. Factors that affect intracellular cAMP concentration, such as secretin, somatostatin, VIP, DBcAMP, and forskolin, did not increase DNA synthesis in cultured pancreatic cells. Insulin and epidermal growth factor induced two- and threefold increases in [3H] thymidine incorporation into DNA, respectively. The effects of insulin were mediated via insulin-like growth factor I receptors. Steroid hormones had little effect on pancreatic acinar cell DNA synthesis. The stimulatory effects of CCK, insulin, and EGF were additive. The combination of caerulein, EGF, and insulin in a hormonally defined medium led to a tenfold increase in the incorporation of [3H]thymidine into DNA. These data indicate that CCK, EGF, and insulin directly increase DNA synthesis in pancreatic acinar cells.
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PMID:Stimulation of pancreatic acinar cell growth by CCK, epidermal growth factor, and insulin in vitro. 302 Sep 92

Plasma GH responses to human GHRH, arginine, L-dopa, and insulin-induced hypoglycemia were determined in seven myotonic dystrophy (MD) patients. An iv bolus injection of GHRH-(1-44)-NH2 (1 microgram/kg BW) only slightly increased plasma GH concentrations in MD patients. The mean peak plasma GH level after GHRH injection [4.2 +/- 0.8 (+/- SE) micrograms/L] was significantly lower than that in 10 age-matched normal subjects (26.7 +/- 4.3 micrograms/L) or that in 6 patients with progressive muscular dystrophy (22.8 +/- 6.6 micrograms/L) whose nutritional status was similar to that of the MD patients. Even with a larger dose of GHRH (3 micrograms/kg BW), the plasma GH rises were minimal in the MD patients (mean peak, 5.9 +/- 1.8 micrograms/L). The plasma GH responses to a 30-min iv infusion of arginine (0.5 g/kg BW) and oral ingestion of L-dopa (0.5 g) were attenuated to a similar extent, whereas insulin-induced hypoglycemia caused a significant increase in plasma GH in all seven MD patients [mean peak, 17.4 +/- 4.1 (+/- SE) microgram/L]. The plasma TSH responses to TRH and plasma insulin-like growth factor I levels were similar in the MD patients and normal subjects. These findings suggest that 1) the impaired GH release after GHRH, arginine, and L-dopa administration in MD patients is not due to somatotroph deficiency, since the GH response to hypoglycemia is well preserved; and 2) insulin-induced hypoglycemia may stimulate GH release at least in part via inhibition of somatostatin release.
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PMID:Discordance between growth hormone (GH) responses after GH-releasing hormone and insulin hypoglycemia in myotonic dystrophy. 314 49


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