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 maternal and fetal endocrine pancreas were investigated in the diabetic BB rat on day 21 of pregnancy. The maternal pancreas of the diabetic rat contained practically no insulin-positive B cells. The A and D cell mass were also decreased, while plasma glucagon and somatostatin levels were normal or increased, confirming previous data. Six of 11 diabetic rats had B-cell-specific surface antibodies (ICSA), whereas only 1 of 10 nondiabetic rats was ICSA-positive. The volume density of insulin-positive cells was decreased in the fetal pancreas of diabetic BB rats compared to fetuses of nondiabetic rats, but the volume density of glucagon- and somatostatin-positive cells remained normal. The B cells of these fetuses were ultrastructurally less granulated and showed signs of increased cellular activity. Plasma insulin levels were decreased while plasma glucagon and somatostatin concentrations were normal. ICSA were not detected in fetuses of nondiabetic and diabetic rats. There were no differences in the histology of the spleen and thymus between both groups of fetuses. Metabolic characterization of the growth-retarded fetuses of diabetic rats revealed, besides lower plasma insulin concentrations, increased branched chain amino acid levels, and normal plasma Sm/IGF-I levels. The main conclusions from this study are: (1) Severe maternal diabetes decreases the pancreatic insulin-positive cell mass and plasma insulin levels in the fetus, but not the A and D cell mass and function; (2) ICSA are not detectable in fetal plasma; (3) the influence of maternal BB rat diabetes on fetal endocrine pancreas and metabolic environment resembles that of severe streptozotocin-induced diabetes.
 ...
PMID:Maternal and fetal endocrine pancreas in the spontaneously diabetic BB rat. 256 32

The effect of a long-acting somatostatin analogue SMS 201-995 on GH secretion was investigated. Eleven acromegalic patients received a single dose of 50 micrograms SMS 201-995 administered subcutaneously, and plasma GH, IGF-I, GRF, TSH, IRI and blood glucose were determined at regular intervals. Nine of 11 patients had elevated basal plasma GH levels above 5 ng/ml. In all patients, plasma GH levels fell immediately from 39.5 +/- 17.3 ng/ml (mean +/- SEM) to 4.3 +/- 1.6 ng/ml (P less than 0.05) with a maximal inhibition of 82.9 +/- 3.3% of the basal levels and the suppression persisted for about 6 h of the observation period. IGF-I and GRF levels were not apparently altered. TSH and IRI levels also rapidly fell. Blood glucose levels fell slightly by 0.5 h. Ten of 11 patients had pain at injection sites. Except for this, no side effects were observed. Our results show that the new somatostatin analogue SMS 201-995 may inhibit GH hypersecretion in acromegalic patients for significant periods, suggesting that this agent can be a useful clinical tool for the treatment of acromegaly.
 ...
PMID:Effect of a single administration of somatostatin analogue (SMS 201-995) on GH, TSH and insulin secretion in patients with acromegaly. 288 93

Growth hormone secretion is controlled by the two hypothalamic hormones, growth hormone releasing factor (GRF) and somatostatin. In addition, the insulin-like growth factors (IGF or somatomedins) which are themselves growth hormone dependent, inhibit growth hormone release in vitro, therefore acting to close the negative feedback loop. The studies reported here examine some of the differences between inhibition of growth hormone secretion by somatostatin and IGF-I in vitro. The major finding is that cycloheximide, a protein synthesis inhibitor, blocks inhibition of GRF-stimulated growth hormone release caused by IGF-I, without changing the inhibition caused by somatostatin. The experiments were done by exposing mixed rat adenohypophysial cells to secretagogues with or without cycloheximide for 24 h in a short term culture. Somatostatin (0.6 nM) totally blocked rat GRF (1 nM) stimulated growth hormone release to values 48% of control (nonstimulated values), while IGF-I (27 nM) only reduced the GRF-stimulated growth hormone release by 27 +/- 3% (N = 5). Cycloheximide (15 micrograms/mL) totally blocked the effect of IGF-I but not somatostatin. A low concentration (0.12 nM) of somatostatin, which only partly inhibited growth hormone release, was also unaffected by cycloheximide. In purified rat somatotrophs, somatostatin (0.1 nM) inhibited GRF-stimulated cAMP levels slightly and reduced growth hormone release while IGF-I (40 nM) had no effect. We suggest that IGF-I inhibits only the secretion of newly synthesized growth hormone, while somatostatin inhibits both stored and newly synthesized growth hormone pools.
 ...
PMID:Cycloheximide blocks insulin-like growth factor I but not somatostatin inhibition of growth hormone secretion. 288 2

We have examined the regulation of GH secretion from monolayer cultures of prepubertal male lamb anterior pituitary cells. Growth hormone-releasing factor (GRF 1-44) stimulated GH release in a dose-related manner: the maximal effective dose was 10(-10) M, which caused a 500% increase in basal GH secretion, while the half-maximal effect was reached with a dose of 2.5 x 10(-11) M (ED50). Thyrotropin-releasing hormone (TRH) also elicited a dose-dependent stimulation of GH secretion, although it was approximately 1000 times less potent than GRF. GRF and TRH did not have additive or synergistic effects on GH secretion. Somatostatin (SRIF) at a concentration of 10(-7) M maximally inhibited basal GH release to 40% of that of the control; the ED50 was 2.0 x 10(-9) M. Moreover, 10(-7) M SRIF blocked the stimulation of GH secretion induced by 10(-8) M GRF. However, when the cells were incubated with these two peptides at an identical concentration (10(-8) M), GH secretion was stimulated significantly above control values. When added at the same concentration (10(-7) M, TRH ans SRIF nullified their respective effects. A dose of 100 ng/ml of synthetic IGF-I was without effect on basal GH release, but significantly decreased 10(-9) M GRF-induced stimulation of GH secretion. these data indicate that in prepubertal male lambs: the stimulatory effect of GRF is predominant over the inhibitory effect of SRIF, somatostatin inhibits TRH stimulation of GH secretion in vitro, and IGF-I may control GH secretion by modulating GRF effects at the pituitary level.
 ...
PMID:Effects of hypothalamic hormones (GRF, TRH, somatostatin) and insulin-like growth factor I on growth hormone secretion from prepubertal male lamb pituitary cultures. 288 68

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.
 ...
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.
 ...
PMID:Medical management of acromegaly due to ectopic production of growth hormone-releasing hormone by a carcinoid tumor. 289 89

A 36-yr-old man with multiple endocrine neoplasia (MEN) type I had an ectopic growth hormone-releasing hormone (GHRH) syndrome due to a GHRH-secreting pancreatic tumor. The immunoreactive (IR)-GHRH concentration in his plasma ranged from 161 to 400 pg/ml (299 +/- 61 pg/ml, mean +/- SD; normal, 10.4 +/- 4.1 pg/ml), and a significant correlation was found between his plasma IR-GHRH and GH (r = 0.622, p less than 0.02). After removal of the pancreatic tumor, the high plasma GH concentration returned to nearly the normal range (42.2 +/- 31.3 to 9.6 +/- 3.8 ng/ml). These changes paralleled the normalization of his plasma IR-GHRH (16.1 +/- 3.8 pg/ml) and some of his symptoms related to acromegaly improved. However, plasma GH (7.7 +/- 1.3 ng/ml) and IGF-I (591 +/- 22 ng/ml) concentrations were high at 12 months after surgery, suggesting adenomatous changes in the pituitary somatotrophs. Before surgery, exogenous GHRH induced a marked increase in plasma GH, and somatostatin and its agonist (SMS201-995) completely suppressed GH secretion, but not IR-GHRH release. No pulsatile secretion of either IR-GHRH or GH was observed during sleep. An apparent increase in the plasma GH concentration was observed in response to administration of TRH, glucose, arginine or insulin, while plasma IR-GHRH did not show any fluctuation. However, these responses of plasma GH were reduced or no longer observed one month and one year after surgery. These results indicate that 1) a moderate increase in circulating GHRH due to ectopic secretion from a pancreatic tumor stimulated GH secretion resulting in acromegaly, and evoked GH responses to various provocative tests indistinguishable from those in patients with classical acromegaly, and 2) the ectopic secretion of GHRH may play an etiological role in the pituitary lesion of this patient with MEN type I.
 ...
PMID:Ectopic growth hormone-releasing hormone (GHRH) syndrome in a case with multiple endocrine neoplasia type I. 289 5

The response to GH releasing hormone (GHRH 1-29) and 24-h serum GH and IGF-I levels were measured in 9 insulin-dependent diabetics with retinopathy and 6 normal volunteers before and after different treatment regimens with octreotide, a long-acting somatostatin analogue. Octreotide, 50 micrograms by sc injection, completely suppressed GHRH-stimulated GH release in both groups. Thrice daily sc injections for up to 20 weeks were associated with variable plasma octreotide levels and failed completely to suppress GH secretion in either the patients or the normal controls. Three days of continuous sc pump infusion (500 micrograms/24-h) resulted in consistently high plasma octreotide levels and completely suppressed 24-h GH in 4 normal subjects, whilst treatment for up to 16 weeks only partially suppressed GH levels in 6 patients (AUC mU.l-1.h-1; 209 +/- 81 vs 121 +/- 82; P = 0.01). Mean +/- SD IGF-I levels (micrograms/l) in the patients (but not controls) were suppressed into the hypopituitary range by median 6 weeks (range 2-16) pump administration (203 +/- 62 vs 60 +/- 25; P = 0.02). Pump treatment achieved total GH suppression in normal subjects; diabetics with retinopathy seem more resistant to the GH suppressing effects of the drug. However, the reduction of serum IGF-I with prolonged treatment may be of clinical value in arresting the progress of diabetic retinopathy.
 ...
PMID:Continuous subcutaneous octreotide infusion markedly suppresses IGF-I levels whilst only partially suppressing GH secretion in diabetics with retinopathy. 291 80

Growth hormone pulse amplitude is intimately connected with growth in childhood. Its effects are most clear in middle childhood, although the influence of adrenal androgens is probably also important. In infancy, nutrition plays an important part and, in the adolescent growth spurt, the synergism with sex steroids is important. Detailed attention needs now to be focussed on the mechanisms by which growth hormone is secreted and has its action; these include the effects of GHRH, somatostatin, insulin and IGF-I.
 ...
PMID:Growth and growth hormone secretion. 305 53

Recent studies in mammalian species indicate that IGF-I may act as a negative feedback inhibitor of GH release through alteration of pituitary secretion or sensitivity to hypothalamic regulatory factors. Although avian GH secretion appears to be regulated by the differential release of hypothalamic inhibitory (somatostatin) and stimulatory (GRF and TRH) factors, feedback effects of IGF-I on in vivo GH release in birds have not been investigated. To study the effects of elevated IGF-I concentration on GRF- and TRH-stimulated GH secretion, 4-week-old chickens received an intravenous injection of recombinant human IGF-I either 15 min prior to (6 micrograms, study 1), or simultaneous with (10 micrograms, study 2). GRF (hGRF44NH2, 5 micrograms/kg) or TRH (0.5 microgram/kg) administration. Radioimmunoassay analysis of plasma collected prior to and following peptide treatment indicated that circulating IGF-I concentrations were elevated 83.9, 60.6, 77.9, and 88.8% at the time of TRH and GRF administration in studies 1 and 2, respectively. Peak GH concentrations (mean of +5- and +15-min samples) subsequent to TRH injection were significantly (P less than 0.01) depressed 45.1 and 48.2% in IGF-I-treated as compared with control chicks in the first and second studies, respectively. GRF-stimulated GH secretion was significantly (P less than 0.01) decreased by IGF-I administration in study 2 (41.3%) but not in study 1. An estimated half-life for IGF-I in the chicken is less than 15 min based on the disappearance rate of the elevation produced by exogenous IGF-I injections. Thus, IGF-I exerts a negative feedback effect on pituitary hormone secretion in avian as well as mammalian species.
 ...
PMID:Effects of insulin-like growth factor I (IGF-I) on growth hormone-releasing factor (GRF) and thyrotropin-releasing hormone (TRH) stimulation of growth hormone (GH) secretion in the domestic fowl (Gallus domesticus). 310 68


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>