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)

The peripheral actions of growth hormone (STH) are mediated by somatomedins or "insulin-like growth factors" (IGF I and II). In untreated acromegaly (n = 24) IGF I was always found increased, IGF II, however, was unchanged. The mean IGF-I-level (+/- SEM) was 553 +/- 75 (range 319-1066) ng/ml in active acromegaly and 193 +/- 10 (range 120-300) ng/ml in control persons. The corresponding IGF-II-values were 533 +/- 38 (range 187-720) and 647 +/- 21 (range 400-900) ng/ml. After treatment of acromegaly IGF I followed changes of the basal STH level with a delay of 4-8 weeks independent of the mode of treatment. This was in contrast to behaviour of IGF II. When STH was suppressible below 1 ng/ml after oral administration of 100 g glucose IGF I was never increased. STH after glucose of more than 5 ng/ml was always associated with increased IGF I. STH values between 1 and 5 ng/ml after glucose were combined with IGF-I-increases in 3 out of 6 cases. Thus, IGF I represents a valuable diagnostic criterion for assessment of activity of acromegaly, particularly in borderline cases, in contrast to IGF II. The criterion of normal somatotrophic function is suggested to be suppressibility of STH level below 1 ng/ml after oral administration of 100 g glucose.
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PMID:[Diagnosis in acromegaly. Insulin-like growth factor as a parameter of activity]. 634 61

GH responses to TRH occur in patients with certain diseases, such as acromegaly, severe liver disease, uremia, and mental disorders, and presumably reflect disruption of normal hypothalamic control of GH secretion. Since histamine (HA) inhibits hypothalamic stimulation of GH secretion, we investigated the combined effect of HA receptor activation and TRH administration on GH secretion in normal men. Eight men were given 4-h infusions of the following: saline, HA, HA plus mepyramine (Me; and H1-antagonist), HA plus cimetidine (C; an H2-antagonist), and C alone. TRH (200 micrograms) was injected iv 2 h after the start of each infusion. HA alone or in combination with either antagonist had no effect on basal or TRH-stimulated TSH secretion and no effect on basal GH secretion. However, when TRH was injected during H1 stimulation by HA plus C, GH secretion increased significantly [from 0.7 +/- 0.1 to 7.1 +/- 1.8 (+/- SEM) ng/ml; P less than 0.01] in seven of eight subjects. This GH response was reproducible and did not occur when saline was administered instead of TRH. A smaller and delayed GH response to TRH occurred during infusions of HA alone (from 0.8 +/- 0.1 to 4.9 +/- 1.0 ng/ml; P less than 0.05). No effect of TRH on GH secretion occurred during the infusion of saline (1.2 +/- 0.3 ng/ml), HA plus Me (0.9 +/- 0.1 ng/ml), or C (2.2 +/- 1.0 ng/ml). There was a significant increase in GH secretion after cessation of the infusions of HA (from 3.4 +/- 1.1 to 7.5 +/- 2.2 ng/ml) and HA plus Me (from 0.8 +/- 0.1 to 5.1 +/- 1.8 ng/ml). This rebound in GH secretion might indicate an inhibitory effect of TRH during H2-receptor stimulation. This concept is supported by the significantly smaller GH response to TRH during HA infusion than during HA plus C infusion (P less than 0.01). The study indicates that H1-receptor stimulation induces a stimulatory effect of TRH on GH secretion in normal men and that H2-receptor stimulation possibly induces an inhibitory effect of TRH on GH secretion.
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PMID:Histamine-induced paradoxical growth hormone response to thyrotropin-releasing hormone in normal men. 642 67

To demonstrate the effect of diazepam on serum growth hormone and prolactin levels in acromegaly, 7 acromegalics were studied. Every patient received 10 mg diazepam orally at zero time, and blood samples were obtained at 30-min intervals. The same patients also underwent a standard L-dopa test. They were given 500 mg L-dopa orally at zero time, and blood samples were obtained at 30-min intervals. The administration of diazepam did not induce any significant changes in either growth hormone or prolactin levels. On the other hand, the administration of L-dopa resulted in a significant decrease in growth hormone level from 74.25 +/- 22 ng/ml (mean +/- SEM) at zero time to a level of 52.8 +/- 21 and 58.77 +/- 22.7 ng/ml at the 60- and 90-min intervals, respectively (p less than 0.05), and a significant decrease in prolactin level from a baseline of 56.18 +/- 17 to 25.5 +/- 8.4 ng/ml (p less than 0.001) at the 60-min interval. It is suggested that the response of growth hormone to diazepam in acromegalics is qualitatively different from nonacromegalic controls.
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PMID:Failure of diazepam to affect growth hormone and prolactin in acromegalics. 664 24

Acromegaloidism is a syndrome characterized by features of acromegaly without biochemical evidence of excessive GH or somatomedin production. We searched for a growth factor in the serum of patients with this syndrome. Growth-promoting activity was measured by determining the stimulatory effect of whole and fractionated serum on colony formation by human erythroid progenitors in vitro. Sera from five subjects with acromegaloidism gave a mean (+/- SEM) stimulated colony growth of 211 +/- 4.0 colonies, in contrast to normal sera which yielded a mean colony growth of 100 +/- 11.0 (n = 9; P less than 0.001). When serum was chromatographed on a Sephadex G-200 column, the maximal stimulation of colony growth was found in the fractions coinciding with the descending slope of the second protein peak. Based on gel filtration chromatography, the estimated molecular weight was 70,000 daltons. Epidermal growth factor, nerve growth factor, fibroblast growth factor, and platelet-derived growth factor resulted in no substantial stimulation of colony growth under the conditions used. Although the erythroid progenitor cells of a Laron dwarf were unresponsive to 200 ng/ml human GH, they were clearly stimulated by serum from a patient with acromegaloidism. The present study describes the presence of a heretofore unidentified growth factor in the serum of subjects with acromegaloidism. This factor also stimulated the erythroid precursor cells of a Laron dwarf whose cells were unresponsive to GH. The physiological role of this growth factor in normal man as well as its pathogenic role in subjects with acromegaloidism remain to be established.
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PMID:A unique growth factor in patients with acromegaloidism. 686 75

It is commonly accepted that hypothalamic dopamine has an inhibitory role not only on prolactin but also on TSH secretion. To study the hypothalamic dopaminergic participation in TSH secretion in various hypothalamo-pituitary disorders, we examined the effect of sulpiride, a dopamine antagonist. Using a commercially available human TSH radioimmunoassay (RIA) kit and improving it, we developed a high sensitivity RIA for human TSH (assay sensitivity: 0.15 micro Units/ml, 50% B/B0 values: 3.47 micro Units/ml). In 18 normal controls, plasma TSH increased significantly after intramuscular injection of sulpiride of 1.01 +/- 0.17 micro Units/ml (Mean +/- SEM). In 61 patients with pituitary adenoma, plasma TSH responses to sulpiride were significantly greater than those of normal controls, and the mean maximal increments were as follows: 1.65 +/- 0.24 micro Units/ml in acromegaly (n = 21), 2.63+/- 0.55 micro Units/ml in non-functioning pituitary adenoma (n = 23), and 4.49 +/- 0.70 micro Units/ml in prolactin producing pituitary adenoma (n = 17), respectively. The maximal TSH responses to sulpiride in prolactin-producing pituitary adenoma were significantly greater than those in non-functioning pituitary adenoma (p less than 0.05) and those in acromegalic patients (p less than 0.001). On the other hand, we could observe no TSH responses to sulpiride in 9 cases of hypothalamic tumor with hyperprolactinemia. These results suggest that the dopaminergic inhibitory influence on TSH secretion is increased in patients with pituitary adenoma, and that it is especially dominant in patients with prolactin producing pituitary adenoma. It is concluded that hypothalamic dopaminergic tone can be evaluated indirectly by the sulpiride test, and that the test is useful in the differential diagnosis of hypothalamo-pituitary disorders.
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PMID:[Effect of sulpiride on plasma TSH secretion in various hypothalamo-pituitary disorders (author's transl)]. 709 11

Thirteen patients with prolactin-secreting and/or growth hormone secreting pituitary tumours have been treated with bromocriptine in doses of about 10 mg/day for several months. Nine of these patients were previously submitted to external or interstitial radiotherapy and one case to pituitary microsurgery. Serum prolactin concentration in patients with prolactinomas was still very high within one year after pituitary irradiation or operation, i.e. 5,125.6 +/- 974 mU/l (mean +/- SEM). It has been reduced to normal level only during bromocriptine therapy, i.e. to 329.1 +/- 88mU/l (p less than 0.001), and increased thereafter, but remained to a significantly lower concentration than before bromocriptine treatment, i.e. 2,709.0 +/- 553 mU/l (p less than 0.05). Serial pneumonecephalotomography has demonstrated the reduction of tumour size afrer bromcriptine therapy to two prolactinomas with suprasellar extension. In patients with acromegaly the effects of bromocriptine were less evident. The antitumoral effects of bromocriptine on prolactin-secreting adenomas is independent and additional to the effects of pituitary radiotherapy or microsurgery, and has therapeuticical implications.
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PMID:Additional antitumoral effects of bromocriptine and radiotherapy in patients with prolactinomas or acromegaly. 720 60

Plasma human prolactin (hPRL) was measured in 73 untreated acromegalic patients and was found to be elevated in 32% of the total population. Hyperprolactinemia was present in 40% of the females and in 27% of the male patients. In both groups, plasma hPRL correlated with plasma human growth hormone (hGH) levels with correlation coefficients of 0.38 (P less than 0.05) for females and 0.41 (P less than 0.005) for males. Forty-five patients were treated with conventional supervoltage pituitary irradiation and evaluated 2, 5, and 10 yr after treatment. The patients with hyperprolactinemia before irradiation showed a decrease in plasma hPRL at the most recent follow-up (mean +/- SEM, 125 +/- 34 vs. 67 +/- 15 ng/ml; P less than 0.01), although, in general, they did not achieve normal values. The patients who had normal plasma hPRL before irradiation (mean +/- SEM, 14 +/- 2 ng/ml) had increased levels after therapy (23 +/- ng/ml; P less than 0.005) but remained in the normal range during long term follow-up. In 10 patients followed for 1-10 yr without treatment, there was a tendency for plasma hPRL to rise progressively (mean increment, 122% above the initial value), with individual changes in hPRL strikingly parallel to the changes in plasma hGH. When serum hPRL was initially elevated, similar responses in both hormones were also seen in a small group of patients treated with surgical hypophysectomy. Galactorrhea was present in 5 of the 25 female patients; in 4 of the 5, plasma hPRL was within the normal range. Overall, these data suggest a closer relationship between hGH and hPRL in acromegaly than had been suspected, not only at the level of pituitary secretion but possibly also at the target cell.
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PMID:Plasma prolactin in acromegaly before and after treatment. 725 17

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

Lipoprotein lipase (LPL) hydrolyzes lipoprotein triglyceride into nonesterified fatty acids, which are then reesterified and stored in adipose tissue. Previous studies have demonstrated increases in LPL in response to insulin-like growth factor I and GH when added in vitro. This study examined the effects of acromegaly treatment on adipose tissue LPL. Ten patients with clinically active acromegaly were recruited. A fasting adipose tissue biopsy was performed both before and 3 months after treatment with octreotide (8 patients) or surgery plus octreotide (2 patients). With treatment, mean baseline insulin-like growth factor I levels fell from 6.41 to 3.98 U/mL (normal, < 2.2 U/mL; P < 0.05), and serum glycohemoglobin fell from 8.6 to 7.2 (normal, < 6.8). Adipose LPL was measured in the heparin-released fraction as well as the cellular fraction extracted with nonionic detergent (EXT). After treatment of acromegaly, there was no change in heparin-released fraction LPL activity or immunoreactive mass. However, there was an increase in EXT activity from 0.73 +/- 0.33 to 1.83 +/- 0.58 nEq/min.10(6) cells (mean +/- SEM; P < 0.05) and an increase in EXT mass from 4.1 +/- 0.89 to 11.4 +/- 2.0 ng/10(6) cells (P < 0.05). There was no change in LPL messenger ribonucleic acid levels with treatment, determined using both quantitative polymerase chain reaction and Northern blotting. Thus, treatment of acromegaly resulted in an increase in the intracellular level of the LPL protein, with no change in messenger ribonucleic acid levels, suggesting posttranscriptional regulation of LPL. These changes in LPL may be due to improved insulin sensitivity, or to other changes associated with acromegaly treatment.
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PMID:Effects of acromegaly treatment and growth hormone on adipose tissue lipoprotein lipase. 759 31

This study was designed to ascertain the long-term safety and efficacy profile of the somatostatin analogue octreotide as treatment of refractory acromegaly. Eight patients (aged 21-62 years) with persistent growth hormone (GH) elevation (duration 1-15 years) despite previous therapy were studied. Octreotide was given subcutaneously in increasing doses for the first year to a maximum of 500 micrograms three times daily. The dose then was reduced to 200 micrograms three times daily for the next 3 years. At annual assessments, 24-h GH profiles, insulin-like growth factor I (IGF-I) and a side-effect profile including gall-bladder ultrasound were studied. Oral glucose tolerance tests (75 g) were performed basally and after 6 months and 3 years of therapy. Haemoglobin A1 (HbA1) was also assessed. Side effects were recorded. Mean GH (+/- SEM) was 36.0 +/- 9 mU/l basally and was reduced significantly at all subsequent assessments on therapy (4-year mean, 9.4 +/- 2.1 mU/l). The IGF-I level also remained suppressed and was normalized in four of eight patients who remained on octreotide. Fasting plasma glucose and HbA1 were not changed by therapy but 2-h glucose was elevated after 6 months and 3 years (basal mean, 7.6 mmol/l (5.3-9.0 mmol/l); 3-year mean, 10.7 mmol/l (8.4-15.7 mmol/l); p < 0.05). Five patients developed gallstones and in three these had disappeared following 1 year of bile salt dissolution therapy. Octreotide continues to suppress serum GH and IGF-I long term without attenuation of effect. Gallstone formation is a major side effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Four years' treatment of resistant acromegaly with octreotide. 771 80


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