Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 21-yr-old woman with Turner's syndrome presented with signs and symptoms of acromegaly. The serum growth hormone (GH) (95+/-9.4 ng/ml; mean+/-SEM) and somatomedin C (11 U/ml) levels were elevated, and an increase in GH levels after glucose instead of normal suppression, increase after thyrotropin-releasing hormone (TRH) administration instead of no change, and decrease after dopamine administration instead of stimulation were observed. The pituitary fossa volume was greater than normal (1,440 mm(3)) and the presence of a pituitary tumor was assumed. After tissue removal at transsphenoidal surgery, histological study revealed somatotroph hyperplasia rather than a discrete adenoma. Postoperatively, she remained clinically acromegalic and continued to show increased GH and somatomedin levels. A search was made for ectopic source of a growth hormone-releasing factor (GRF). Computer tomographic scan revealed a 5-cm Diam tumor in the tail of the pancreas. Following removal of this tumor, serum GH fell from 70 to 3 ng/ml over 2 h, and remained low for the subsequent 5 mo. Serum somatomedin C levels fell from 7.2 to normal by 6 wk postoperatively. There were no longer paradoxical GH responses to glucose, TRH, and dopamine. Both the medium that held the tumor cells at surgery and extracts of the tumor contained a peptide with GRF activity. The GRF contained in the tumor extract coeluted on Sephadex G-50 chromatography with rat hypothalamic GH-releasing activity. Stimulation of GH from rat somatotrophs in vitro was achieved at the nanomolar range, using the tumor extract. The patient's course demonstrates the importance of careful interpretation of pituitary histology. Elevated serum GH and somatomedin C levels in a patient with an enlarged sella turcica and the characteristic responses seen in acromegaly to TRH, dopamine, and glucose do not occur exclusively in patients with discrete pituitary tumors and acromegaly. This condition can also occur with somatotroph hyperplasia and then revert to normal after removal of the GRF source. Thus, in patients with acromegaly a consideration of ectopic GRF secretion should be made, and therefore, careful pituitary histology is mandatory. Consideration for chest and abdominal computer tomographic scans before pituitary surgery, in spite of their low yield, may be justified.
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PMID:Somatotroph hyperplasia. Successful treatment of acromegaly by removal of a pancreatic islet tumor secreting a growth hormone-releasing factor. 629 May 40

Human pancreatic GRF (hpGRF-40; 1 microgram/kg, iv) selectively stimulates GH release in normal men (9). We now report the effects of graded doses of hpGRF-40 on GH release in 12 normal men. Mean peak increments in serum GH after vehicle and the various doses of hpGRF-40 were 1.13, 11.40, 14.60, 17.01, 14.45, and 15.60 ng/ml after vehicle and 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40 (iv bolus), respectively. Peak values were observed 30-60 min after hpGRF-40 treatment. There was considerable variability of responsiveness among individual subjects, and no dose-response relationship between the doses and maximal GH values was found. However, the higher doses of 3.3 and 10.0 micrograms/kg resulted in a more prolonged and biphasic pattern of GH release. A side effect of facial flushing of less than 5-min duration occurred in 4 or 6 subjects who received 3.3 micrograms/kg and in all 5 who received 10 micrograms/kg of hpGRF-40. No changes in serum glucose, LH, TSH, PRL, plasma cortisol, or 8 enteropancreatic hormones occurred after hpGRF-40 treatment. There were small increases in serum somatomedin C levels 24 h after the administration of various doses of hpGRF-40 in 11 of 13 studies. Plasma immunoreactive GRF levels measured 5 min after injection were 0.09, 2.0, 4.9, 23.9, and 66.6 ng/ml after 0.1, 0.33, 1.0, 3.3, and 10 micrograms/kg hpGRF-40, respectively. Serum GH responses after insulin-induced hypoglycemia were compared to GH responses after hpGRF-40. Comparable peak GH stimulation occurred with both provocative tests. Mean +/- SEM peak GH was 20.2 +/- 1.0 ng/ml after insulin and 20.9 +/- 3.2 after hpGRF-40 treatment. hpGRF-40 selectively stimulates GH release in normal men over a dose range of 0.1-10 micrograms/kg and is an effective probe to investigate the dynamics of GH release.
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PMID:Human pancreatic tumor growth hormone-releasing factor: dose-response relationships in normal man. 642 60

Immunoreactive growth hormone-releasing factor was detected in extracts of acetone preserved human stalk median eminence utilizing an antiserum against human GRF-(1-44)-NH2, isolated from a pancreatic tumor. The antibody is highly specific for the C-terminus of GRF-(1-44)-NH2, and has a cross-reactivity less than 0.02% with GRF-(1-40) free acid, a peptide isolated from a different pancreatic tumor. The mean concentration of IR-GRF in 5 pools of 10-15 stalk-median eminence fragments was 57.7 +/- 7.2 ng/mg protein (mean +/- SEM, range 42.5-75.8 ng/mg protein). Gel filtration chromatographic analysis showed that 97% of the IR-GRF coeluted with synthetic hpGRF-(1-44)-NH2 and eluate inhibition of binding in the radioimmunoassay was parallel to that of hpGRF-(1-44)-NH2. These data strongly suggest that human hypothalamic tissue contains a peptide that is similar to hpGRF-(1-44)-NH2.
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PMID:Immunoreactive growth hormone-releasing factor in human stalk median eminence. 642 65

We have raised antibodies to rat growth hormone-releasing factor (GRF) which, when acutely administered to rats, cause a complete inhibition of pulsatile GH release. Using this passive immunization technique, we have evaluated the role of GRF in normal somatic growth. Twenty-two-day-old male Sprague-Dawley rats (61 +/- 2 g, mean +/- SEM) were treated for 16 days with either normal rabbit serum (n = 7) or rabbit antiserum raised against GRF (n = 7). During this period the BW of rats treated with normal rabbit serum increased 8.3 +/- 0.4 g/day while rats treated with GRF antiserum increased 4.3 +/- 0.2 g/day (P less than 0.01). These rats were then left untreated for an additional 22 days to determine whether animals treated with GRF antiserum would demonstrate a period of catch-up growth. Rats treated with normal rabbit serum continued to increase in BW at 8.1 +/- 0.4 g/day. Remarkably, rats treated with GRF antiserum continued to have a reduced growth rate, 5.4 +/- 0.6 g/day (P less than 0.01). This reduced growth rate was not due to long-term suppression of GH, since the patterns of pulsatile secretion and concentrations of plasma GH were not different between the two groups when measured three weeks after termination of the GRF antiserum treatment. These results demonstrate that GRF has a primary role in somatic growth and suggest that its presence during postnatal development is required to ensure subsequent normal somatic growth.
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PMID:Antibodies to growth hormone-releasing factor inhibit somatic growth. 643 Jun 84

The interaction between the inhibitory effect on growth hormone secretion of a 75 g oral glucose load and the stimulatory effect of human pancreatic growth hormone releasing factor 1-44 (hpGRF 1-44, 10 micrograms i.v.) has been studied in six normal subjects. hpGRF 1-44 alone induced a rise in growth hormone concentrations (maximum mean +/- SEM, 16.5 +/- 1.7 mU/l 15 min after injection) while growth hormone levels were suppressed by oral glucose alone (less than 1.5 mU/l from 45 to 135 min after glucose ingestion). When hpGRF 1-44 was injected 60 min after oral glucose, the growth hormone response was attenuated (maximum, 6.7 +/- 1.4 mU/l at 15 min, P less than 0.05). Increments of blood glucose within the physiological range diminish the growth hormone response to hpGRF 1-44 in normal man.
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PMID:Oral glucose inhibits growth hormone secretion induced by human pancreatic growth hormone releasing factor 1-44 in normal man. 643 36

Synthetic human pancreatic growth hormone-releasing factor (hpGRF-44) was infused intravenously at a constant rate of 2.5 micrograms/min for 180 minutes in 3 normal boys of short stature. Plasma GH levels reached a peak at 60-120 min with a mean value (+/- SEM) of 69.1 +/- 14.3 ng/ml, and then, declined gradually in spite of continuous hpGRF-44 infusion up to 180 minutes. Similarly, constant infusion of hpGRF-44 at a rate of 2.5 micrograms/min in 5 normal but short boys for 90 minutes, together with an iv bolus injection of hpGRF-44 (2 micrograms/kg) administered at 0 and 90 minutes, elicited a prompt rise in plasma GH 15-30 minutes after the first bolus but no significant elevation of GH was observed after the second bolus. In contrast, when two iv bolus injections of hpGRF-44 (2 micrograms/kg) were given in 4 normal boys with short stature at 0 and 90 minutes, respectively, significant elevation of plasma GH was found after each bolus. These results suggest that under constant infusion of GRF the pituitary experiences a down-regulation after the initial peak of GH response, possibly due to desensitization to GRF.
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PMID:Plasma growth hormone secretion during constant growth hormone-releasing factor infusion. 644 96

The distribution of 15-micron microspheres was measured in rat kidneys before and after the animals had undergone either isovolemic hematocrit increase or isovolemic hematocrit decrease. Raising the systemic arterial hematocrit from 46 +/- 1% (mean +/- SEM) to 59 +/- 1% caused a significant decrease in the rate of urinary sodium and potassium excretion (UNaV, UKV), but not significant changes in total renal blood flow (RBF), filtration fraction (FF), outer cortical flow, inner cortical flow, or rate of urinary volume excretion (V). Fractional sodium excretion was also unchanged suggesting that the decreased UNAV was the result of a decreased glomerular filtration rate (GFR). The measured decrease in GFR was not statistically significant. Lowering the systemic hematocrit from 45 +/- 1% to 33 +/- 1% caused a significant fall in FF as well as significant increases in the rate of urine volume excretion (V), UNaV, UKV, and GRF. There was a significant increase in RBF but again no change in the flow distribution between inner and outer cortex. The findings show that hematocrit alterations alone do not immediately lead to a redistribution of blood flow between inner and outer cortex of the rat kidney.
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PMID:Renal blood flow distribution measured by microspheres during isovolemic hematocrit alteration in rats. 738 87

In the dog endogenous progesterone and synthetic progestins may incite overproduction of GH, resulting in acromegaly and insulin resistance. This progrestin-induced excessive GH secretion is characterized by disappearance of the pulsatile secretion pattern and insensitivity to both stimulation with GHRH and inhibition with a somatostatin analog. This progestin-induced GH hypersecretion is not associated with neoplastic transformation at the pituitary level. These observations were the impetus for a search of a possible extrapituitary site of GH production. In four ovariohysterectomized dogs elevated plasma GH levels (46.5 +/- 7.7 micrograms/liter; mean +/- SEM) were induced by administration of synthetic progestins. In these dogs hypophysectomy did not led to a significant decrease in plasma GH levels. Analysis of the GH content of various tissue homogenates revealed that the highest GH immunoreactivity was found in extracts of the mammary gland. Ectopic production of GH in the mammary gland was confirmed by lowering of plasma GH concentration to values within the reference range within 2 h after complete mammectomy in two dogs with progestin-induced elevations of plasma GH levels. In one of these dogs the arterial and elevations of plasma GH levels. In one of these dogs the arterial and venous GH concentrations across the mammary gland were measured and an arterio-venous GH gradient was demonstrated. Displacement studies in the RIA and analysis by reversed-phase HPLC revealed that mammary-derived GH is highly similar to pituitary-derived GH. Immuno-histochemical staining revealed that GH immunoreactivity was localized in focal areas of hyperplastic ductular epithelium. In mammary tissue of healthy untreated female dogs no GH immunoreactivity was found. It is concluded that treatment of dogs with synthetic progestins can induce the overproduction of GH in the mammary gland. This GH is biologically active, highly similar to pituitary derived GH, and originates from foci of hyperplastic ductular epithelium of the mammary gland.
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PMID:Progestin-induced growth hormone excess in the dog originates in the mammary gland. 750 6

The aim of the study was to elucidate the role of the neuropeptide galanin in the regulation of somatotropic and gonadotropic function in normal women. Thirteen normally ovulating (aged 28 to 40 years), non-obese (body mass index, 18.4 to 27.1 kg/m2) women with infertility due to a tubal or male factor were studied. Each woman underwent three tests: (1) bolus intravenous (IV) injection of growth hormone (GH)-releasing hormone (GHRH) (1-29)NH2 1 microgram/kg plus gonadotropin-releasing hormone (GnRH) 100 micrograms at time 0; (2) IV infusion of porcine galanin 500 micrograms in 100 mL saline from -10 minutes; and (3) bolus IV injection of GHRH(1-29)NH2 1 microgram/kg plus GnRH 100 micrograms at time 0 plus IV infusion of porcine galanin 500 micrograms in 100 mL saline from -10 to +30 minutes. All results are expressed as the mean +/- SEM. GH peak after GHRH was 14 +/- 5 micrograms/L; porcine galanin significantly increased serum GH (GH peak, 7.3 +/- 1.2) with respect to baseline levels. No significant differences were observed between either GH peak or GH absolute values after galanin as compared with GHRH alone. Porcine galanin significantly enhanced GH response to GHRH (peak, 31.4 +/- 4.4 micrograms/L) with respect to either GHRH or galanin alone. Luteinizing hormone (LH)/follicle-stimulating hormone (FSH) peaks after GnRH were 16.5 +/- 5.3 and 17.4 +/- 4 IU/L, respectively. Porcine galanin did not cause significant increases in serum LH and FSH levels with respect to baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of galanin in the regulation of somatotrope and gonadotrope function in young ovulatory women. 754 51

Growth hormone-releasing peptide 6 (GHRP-6) is a synthetic hexapeptide with a potent GH-releasing activity after intravenous, subcutaneous, intranasal and oral administration in man. Previous data showed its activity also in some patients with GH deficiency. The aim of our study was to verify the GH-releasing activity of oral GHRP-6 administration on GH secretion in children with normal short stature. The effect of oral GHRP-6 (300 micrograms/kg) was compared with that of the maximally effective dose of intravenous GH-releasing hormone (GHRH-29, 1 microgram/kg). As the GHRH-induced GH rise in children is potentiated by arginine (ARG), even when administered by oral route at low dose (4 g), we studied also the interaction of oral GHRP-6 and ARG administration. We studied 13 children (nine boys and four girls aged 6.2-10.5 years, pubertal stage I) with normal short stature (height less than -2 SD score; height velocity more than -2 SD score; normal bone age; insulin-like growth factor I > 70 micrograms/l). In a first group of children (N = 7), oral GHRP-6 administration induced a GH response (mean +/- SEM; peak at 60 min vs baseline: 18.8 +/- 3.0 vs 1.1 +/- 0.3 micrograms/l, p < 0.0006; area under curve: 1527.3 +/- 263.9 micrograms l-1 h-1) which was similar to that elicited by GHRH (peak at 45 min vs baseline: 20.8 +/- 4.5 vs 2.2 +/- 0.9 micrograms/l, p < 0.007; area under curve: 1429.4 +/- 248.2 micrograms l-1 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth hormone-releasing effect of oral growth hormone-releasing peptide 6 (GHRP-6) administration in children with short stature. 758 65


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