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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the effects on carbohydrate metabolism of human GH produced by recombinant DNA technology (methionyl-hGH) compared with pituitary hGH. Twelve normal adult male subjects received four daily im injections of either methionyl-hGH or pituitary hGH in a double blind, crossover study. Oral glucose tolerance tests and assays of insulin binding to peripheral monocytes were performed before th initial administration and 12 h after the fourth injection of both hGH preparations. Both methionyl-hGH and pituitary hGH resulted in significant carbohydrate intolerance, with a rise in fasting plasma glucose from 96.6 +/- 2.9 to 105.9 +/- 3.0 mg/ml (mean +/- SEM) after pituitary hGH and from 96.2 +/- 1.5 to 107.5 +/- 3.3 mg/dl after methionyl-hGH (P less than 0.01). The area under the glucose tolerance curve increased by 34% after pituitary hGH and by 37% after methionyl-hGH. With both hGH preparations, carbohydrate intolerance was associated with marked hyperinsulinemia, with a rise in fasting plasma insulin levels from 9.4 +/- 1.2 to 33.2 +/- 7.8 microU/ml after pituitary hGH and from 7.4 +/- 1.1 to 45.8 +/- 11.1 microU/ml after methionyl-hGH (P less than 0.01). The integrated plasma insulin levels during the oral glucose tolerance test tripled after both hGH preparations. The pronounced insulin resistance could not be attributed to an alteration in insulin receptor concentrations. Both hGH preparations were associated with small reductions in insulin binding to monocytes at tracer concentrations, but the decline in binding was not statistically significant. The calculated binding sites per cell and Ke were not significantly altered by hGH administration. We conclude that methionyl-hGH and pituitary hGH are indistinguishable in their ability to induce insulin-resistant carbohydrate intolerance. This decrease in insulin sensitivity cannot be attributed to an alteration in insulin binding, and presumably represents a postreceptor defect in insulin action.
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PMID:Both human pituitary growth hormone and recombinant DNA-derived human growth hormone cause insulin resistance at a postreceptor site. 703 19

Plasma and red blood cell folacin concentrations (Lactobacillus casei activity) and other pertinent parameters have been studied in 10 infants and children fed home-made cow's milk mixtures until 5 months of age. The folacin concentrations have been estimated in 44 samples of pasteurized cow's milk before and after pretreatment with conjugase. The effect of boiling on the folacin concentration has been studied in 11 samples of pasteurized cow's milk. During the time the infants were fed home-made cow's milk mixtures they developed signs of folacin deficiency, as judged from the plasma and red cell folacin concentrations as well as from other hematologic studies. The mean folacin concentration in pasteurized cow's milk was 168.9 SEM 7.80, and range 72 to 262 nmol/liter. Pretreatment with conjugase did not increase the folacin concentrations. During boiling for 1 min 2/3 of the folacin activity was lost. This could be prevented by adding ascorbic acid, 1 mg/ml, before the boiling procedure. The folacin deficiency observed in the infants is probably secondary to loss of folacin activity in connection with the preparation of the cow's milk mixtures.
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PMID:Plasma and red cell folacin in cow's milk-fed infants and children during the first 2 years of life: the significance of boiling pasteurized cow's milk. 738 12

The embryonic chicken cartilage somatomedin bioassay was modified so that human serum stimulation of simultaneous [3H]methylthymidine and H2[35S]O4 incorporation could be assessed. The assay consisted of a 6 h pre-incubation of 10 day pelvic rudiments in enriched buffer, followed by a 24 h incubation with buffer and low (0.5, 2 and 5% v/v) serum concentrations. Both labels were present for the final 6 h. Other modifications were shortening of washing, elimination of drying and weighing, and simplification of digestion. Normal human serum produced a linear log dose-response with these serum concentrations. Potency ratios in patients with GH deficiency were less than those of normal adults for both thymidine 0.39 +/- 0.05 (mean +/- SEM, n = 16, range 0.22-0.71) vs. 0.90 +/- 0.05 (n = 19, 0.62-1.36, P < 0.001) and for sulphate 0.40 +/- 0.04 (0.15-0.65) vs. 94 +/- 0.05 (0.61-1.29, P < 0.001). Potency ratios for both labels rose following administration of a single dose (0.2 IU/kg im) of hGH to 4 GH deficient children. The reliability of prediction of GH deficiency, reproducibility, and precision were similar to other Sm bioassays. The major advantages of these modifications were the ability to examine 2 cartilage metabolic processes simultaneously and the small amount of serum (350 mul) necessary for patient assays.
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PMID:Growth hormone dependent human serum stimulation of thymidine and sulphate incorporation into embryonic chicken cartilage. 743 10

To test the hypothesis that a dysfunctional growth hormone (GH)-insulin-like growth factor (IGF) axis may play a role in the pathogenesis of osteoporosis, we compared the levels of IGF-I, IGF-II and IGF binding protein 3 (IGFBP-3) in 15 women with spinal osteoporosis (i.e. at least one non-traumatic vertebral fracture) and 15 normal age-matched women. Furthermore, the response to 3 days' treatment with recombinant human GH (r-hGH) (0.2 IU kg-1.day-1) was determined. The basal levels of IGF-I, IGF-II and IGFBP-3 were similar in patients and controls (mean +/- SEM): IGF-I, 16.5 +/- 1.3 versus 16.0 +/- 1.3 nmol/l (NS); IGF-II, 79.9 +/- 3.6 versus 72.5 +/- 4.1 nmol/l (NS); and IGFBP-3, 125.7 +/- 6.5 versus 130.3 +/- 7.8 nmol/l (NS). Stimulation with r-hGH elicited increased levels of IGF-I, IGF-II and IGFBP-3 within both groups (p < 0.001). The maximal values expressed as a percentage of baseline were: IGF-I, 341 +/- 26% versus 369 +/- 22%, IGF-II, 125 +/- 4% versus 119 +/- 5%, IGFBP-3, 141 +/- 5% versus 147 +/- 7% in osteoporotic patients and controls, respectively. No significant differences were observed between patients and controls in either their maximal response or in the area under the response curves. Our results do not support the hypothesis of a dysfunctional GH-IGF axis in women with spinal osteoporosis.
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PMID:No evidence for reduced spontaneous or growth-hormone-stimulated serum levels of insulin-like growth factor (IGF)-I, IGF-II or IGF binding protein 3 in women with spinal osteoporosis. 752 Dec 46

Removal of a craniopharyngioma usually results in panhypopituitarism. Some children, however, grow normally or even excessively after extirpation of the tumor despite a proven lack of GH and have so far not been treated with hGH. We studied the effects of short (2-day) and long term (1-yr) administration of hGH on metabolism and growth in six patients receiving regular hormonal replacement therapy. During short term human (h) GH treatment, 15N retention was not significantly increased (mean +/- SEM, 115.4 +/- 9.6% of basal balance) and was not different from the control value. In contrast, 15N retention was 210.3 +/- 20.7% in children with GH deficiency from other causes. Long term administration of hGH (2 IU/m2.day, sc, for 12 months) did not influence growth velocity, but increased the calf circumference and decreased the body mass index and skinfold thickness in prepubertal patients. Insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), and the 150-kilodalton IGFBP complex were decreased before and restored to normal during treatment. The reverse was observed for the 50-kilodalton IGFBP complex. Growth (velocity) in these patients did not correlate with any of the usual indicators of the growth status and remains unexplained. Although hGH did not affect growth, it had other beneficial effects and is recommended for these patients.
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PMID:Replacement of growth hormone (GH) in normally growing GH-deficient patients operated for craniopharyngioma. 785 93

To clarify the roles of the rat placental lactogens in embryogenesis and fetal development, we measured the concentrations of rat placental lactogen-II (rPL-II) in fetal rat serum and examined the distribution and expression of rPL-I- and rPL-II-binding sites in rat uteroplacental and fetal tissues. The concentration of rPL-II in fetal rat serum on day 20 of gestation was 28.3 +/- 0.8 ng/ml (mean +/- SEM; n = 6), approximately 1/14th its concentration in maternal serum (398.3 +/- 45.3 ng/ml; n = 6). In the midgestational uterus and placenta, rat PL-I bound specifically to mesometrial decidua and to a capsular layer of stroma overlying the antimesometrial decidua. The binding of radiolabeled rPL-I to these tissues was inhibited by unlabeled rat PRL and human (h) GH, but not by rat GH, suggesting that the rPL-I-binding sites are lactogenic in nature. In the late gestational fetus, rat PL-II bound specifically to fetal adrenal, kidney, small intestine, liver, and pancreas; its binding, like that of rPL-I, was inhibited by rPRL, but not by rGH. rPL-II-binding sites in fetal adrenal were detected as early as day 16, whereas rPL-II-binding sites in fetal kidney and small intestine were not demonstrable until day 18. Lactogenic binding sites in fetal liver and pancreas did not appear until days 19-20. The relative amounts of specific binding of rPL-II to fetal tissues correlated positively with tissue levels of expression of the 4.2- and 1.8-kilobase PRL receptor mRNA transcripts. Radiolabeled hGH, which interacts with somatogenic receptors as well as lactogenic receptors, bound specifically to mesometrial decidua, fetal adrenal, kidney, small intestine, liver, and pancreas. In addition, radiolabeled hGH bound specifically, but with low intensity, to fetal brain. In mesometrial decidua and fetal adrenal, kidney, and small intestine, the binding of hGH was blocked by rPL-II and rPRL, but not by rGH or ovine GH, suggesting the predominance of lactogenic receptors. In contrast, in fetal brain, the binding of hGH was inhibited by rGH, but not by rPL-II, suggesting that the fetal brain contains somatogenic receptors. The presence of rPL-I-binding sites in maternal decidua suggests a paracrine role for the hormone in decidual function at midgestation. The presence of rPL-II in fetal serum and the widespread distribution of rPL-II-binding sites in fetal tissues indicate a role for rPL-II in fetal development.
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PMID:Pregnancy lactogens in the rat conceptus and fetus: circulating levels, distribution of binding, and expression of receptor messenger ribonucleic acid. 840 26

We investigated the relationship between urinary growth hormone (u-GH) and spontaneous 24-hour plasma GH secretion in 15 acromegalic patients. To measure u-GH, we have developed a method based on concentrating the sample by centrifugal ultrafiltration and then performing an immunoradiometric assay using commercially available reagents. u-GH correlated well with the integrated concentration of plasma GH (r = 0.66, p < 0.02). Additionally, u-GH excretion in acromegalic patients was significantly higher than in the control group (190 +/- 100 vs. 3.89 +/- 0.56 pg/min, mean +/- SEM, p < 0.001). Immunoreactive u-GH showed the same elution pattern in Sephadex G-75 as standard or labeled hGH, proving that the substance measured in urine is authentic GH. In conclusion, u-GH appears to be a simple, noninvasive and inexpensive test for evaluating GH secretion in active acromegaly.
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PMID:Usefulness of urinary growth hormone (GH) measurement for evaluating endogenous GH secretion in acromegaly. 840 34

Dwarf tyrosine hydroxylase-human GH (TH-hGH) transgenic mice carrying the hGH reporter gene targeted by the TH promoter express hGH in those regions of the hypothalamus responsible for regulation of pituitary GH secretion. Central expression of the hGH gene decreases GH-releasing hormone (GHRH) and increases somatostatin, which ultimately impacts on pituitary function by reducing the overall amount of GH produced. In the present study, we sought to determine if the reduction of pituitary GH in TH-hGH mice could be attributed to a decrease in somatotrope cell numbers and/or an impairment of somatotrope function. Pituitaries from TH-hGH or wild-type (WT) male and female mice were enzymatically dispersed, counted, and immunostained for GH, PRL, TSH, and ACTH. The total number of pituitary cells recovered from TH-hGH pituitaries was approximately one-half of that from WT controls. However, the proportion of cells that stained for GH and PRL were virtually identical (males, GH-TH-hGH, 58.1 +/- 1.0% [mean +/- SEM] vs. WT, 60.7 +/- 1.0%; PRL-TH-hGH, 43.4 +/- 2.2% vs. WT, 43.1 +/- 0.7%; females, GH-TH-hGH, 47.9 +/- 2.3% vs. WT, 41.5 +/- 3.5%; PRL-TH-hGH, 43.3 +/- 3.2% vs. WT, 47.1 +/- 3.3%). In contrast, percentages of both TSH- and ACTH-containing cells were increased in TH-hGH pituitaries relative to controls (males, TSH-TH-hGH, 15.1 +/- 2.3% vs. WT, 9.6 +/- 1.5%; ACTH-TH-hGH, 24.5 +/- 2.5% vs. WT, 10.9 +/- 0.9%; females: TSH-TH-hGH, 11.3 +/- 0.7% vs. WT, 7.5 +/- 0.6%; ACTH-TH-hGH, 19.8 +/- 1.6% vs. WT, 9.3 +/- 0.8%; P < 0.05). Calculation of the absolute number of each cell type per pituitary demonstrated TH-hGH mice to have about one-half the number of GH and PRL cells, whereas TSH and ACTH cell populations were comparable with that of their WT counterparts. Immunocytochemical localization of GH cells within pituitary sections from TH-hGH mice revealed that somatotropes were confined primarily to the lateral wings of the adenohypophysis, in contrast to the heterogeneous distribution of GH-immunostained cells in WT pituitaries. To assess the functional capacity of the somatotrope populations, pituitary cells from TH-hGH and WT mice were challenged with mouse GHRH (0.01-10 nM). The quantity of GH released (as assessed by both RIA and reverse hemolytic plaque assay) under basal and stimulated conditions did not differ among TH-hGH and WT pituitary cell cultures. Similarly, GHRH induced intracellular cAMP levels were comparable. These results indicate that proliferation of pituitary somatotropes and lactotropes is much more sensitive to changes in GHRH input than is the capability of developing regulated GH secretory function.
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PMID:The tyrosine hydroxylase-human growth hormone (GH) transgenic mouse as a model of hypothalamic GH deficiency: growth retardation is the result of a selective reduction in somatotrope numbers despite normal somatotrope function. 889 26

The aim of this study was to verify the persistence in adulthood of GH deficiency diagnosed in childhood and treated with hGH in childhood and to study whether anatomical hypothalamic-pituitary alterations evaluated by magnetic resonance (MR) imaging could predict it. To this goal, in six GHD adults (3 males and 3 females aged 17.2-24.5 yr, BMI 21.8 +/- 1.3), we studied anterior pituitary hormone response to GHRH (1 microgram/kg iv)+pyridostigmine (120 mg po)+ GnRH (100 micrograms iv) +TRH (400 micrograms iv)+hCRH (100 micrograms iv) as well as brain MR imaging. In childhood, the diagnosis of severe isolated GHD had been done based on auxological findings as well as on GH response < 7 micrograms/L after two classical provocative stimuli. In the present study, hormonal responses showed the persistence of severe isolated GHD in 4 out of 6 patients (peak, mean +/- SEM: 3.8 +/- 0.6, range 2.6-4.8 micrograms/L). In these patients, IGF-I levels were found low or low-normal. In other 2 patients, a clear GH response to stimulation (peak: 51.3 and 43.0 micrograms/L, respectively) together with normal IGF-I levels were found. No other anterior pituitary hormone deficiency was present in all subjects. MR imaging showed pituitary hypoplasia in all patients with persistent GHD; in 2 out of them, pituitary stalk interruption and ectopic neurohypophysis was also present. On the other hand, MR imaging showed normal hypothalamo-pituitary morphology in the 2 subjects with normal somatotrope response. In conclusion, our present data indicate that testing with a potent stimulus such as GHRH+pyridostigmine is a reliable method to assess the persistence of GH deficiency which associates with anatomical hypothalamic-pituitary alterations at the MR imaging. Patients with transient GH deficiency in childhood and normal pituitary GH reserve in adulthood have normal hypothalamic-pituitary MR imaging.
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PMID:Is the persistence of isolated GH deficiency in adulthood predicted by anatomical hypothalamic-pituitary alterations? 929 76


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