Growth-promoting Actions Of Growth Hormone Research Articles

524 In vitro evaluation of phototoxic properties of systemic antipsoriatics

524 In vitro evaluation of phototoxic properties of systemic antipsoriatics

Effects of Oral Administration of Insulin-Like Growth Factor-I on Circulating Concentration of Insulin-Like Growth Factor-I and Growth of Internal Organs in Weanling Mice

Insulin-like growth factor (IGF)-I is a polypeptide that mediates the growth-promoting action of growth hormone in postnatal animals. The present study was conducted to examine whether orally administered IGF-I would be absorbed into the general circulation and also whether ingested IGF-I would enhance the growth of whole body as well as internal organs, and tissues in 3-week-old ICR-strain female weanling mice. In experiment (Exp) 1, a total of 70 mice received IGF-I orally at 1 µg·g^–1 in 0.2-ml PBS or the vehicle alone. Concentrations of IGF-I and glucose in heart blood were measured after killing 5 animals in each group every fourth hour during a 24-hour period. In Exp 2, a total of 40 mice received oral IGF-I administration at 1 µg·g^–1 or vehicle every third day beginning from day 0 for a 13-day period. Half the animals were killed at day 7 and the other half at day 13. Weights of whole body and organs/tissues (small intestine, liver, thigh muscle, and brain) were measured every day and at slaughter, respectively. In Exp 1, following the oral IGF-I administration, serum IGF-I concentration increased at hour 4 (p < 0.01) and returned to the hour 0 level by hour 8, whereas glucose concentration was lowest at hour 4 and returned to the hour 0 level by hour 16. In the PBS-fed group, neither IGF-I nor glucose concentration changed during the 24-hour period. In Exp 2, weight of small intestine increased (p < 0.05) in response to the oral IGF-I, whereas weights of liver and thigh muscle of the IGF-I-fed group were greater (p < 0.01) and tended to be greater (p = 0.06), respectively, than those of the PBS-fed only at day 13. However, brain weight and serum concentrations of IGF-I and IGF-II were not affected by oral IGF-I administration. Results suggest that although orally administered IGF-I mainly acts at the intestine, a portion of ingested IGF-I is absorbed into the general circulation to enhance the growth of selective organs/tissues in weanling mice.

More questions about growth hormone in Crohn disease.

More questions about growth hormone in Crohn disease.

IGF-I Does Not Mediate T-Lymphoblast Colony Formation in Response to Estradiol, Testosterone, 1,25(OH)2Vitamin D3, and Triiodothyronine: Studies in Control and Pygmy T-Cell Lines

The mechanism by which estradiol, testosterone, 1,25(OH)2vitamin D3, and triiodothyronine promote tissue growth is unknown, although, in some tissues, a role for local IGF-I has been suggested. We previously showed that HTLV-II-transformed T-cell lines from healthy adults augmented basal colony formation in response to peptide (growth hormone, parathormone, and adrenocorticotrophin) and glycoprotein (thyroid-stimulating hormone) hormones through stimulation of local IGF-I. T-cell lines from African Efe Pygmies, however, were resistant to the direct growth-promoting action of IGF-I, as well as to the growth-promoting action of growth hormone, parathormone, adrenocorticotrophin, and thyroid-stimulating hormone. We, therefore, used these cell lines to determine the mechanism of T-cell growth in response to steroid and thyroid hormones. We quantified colony formation of American control T-cell lines in the presence and absence of αIR-3 antibody against the type 1 IGF receptor and Pygmy T-cell lines in response to estradiol (36.7–1835 pmol/ liter), testosterone (34.7–17,350 pmol/liter), 1,25(OH)2vitamin D3(2.4–24,000 pmol/liter), and triiodothyronine (1536–192,000 pmol/liter). There were no statistically significant differences by ANOVA in overall response curves for any of the four hormones comparing control clonal responses in the presence or absence of αIR-3 and no statistically significant difference in overall responsiveness between control and Pygmy T-cell lines. From these data, we conclude that (i) normal T-cell lines grow in response to estradiol, testosterone, 1,25(OH)2vitamin D3, and triiodothyronine; (ii) these responses are not mediated through local IGF-I since they are not blocked by pretreatment with antibody to the type 1 IGF receptor; and (iii) Pygmy T-cell lines, which are genetically resistant to IGF-I, grow equivalently to control T-cell lines in response to estradiol, testosterone, 1,25(OH)2vitamin D3, and triiodothyronine, further underscoring the IGF-I independence of this stimulation in our system.

THE MECHANISMS BY WHICH GROWTH HORMONE BRINGS ABOUT GROWTH: The Relative Contributions of Growth Hormone and Insulin-Like Growth Factors

Growth hormone is the major regulator of postnatal growth. Although intrauterine growth seems to be largely growth hormone independent, gene knockout studies have established the pivotal role of the IGF system in both prenatal and postnatal growth. The original "somatomedin hypothesis" postulated that all of the growth-promoting actions of growth hormone were mediated by IGFs. Several in vitro and in vivo studies have suggested, however, that growth hormone may have specific growth-related actions in addition to stimulating IGF production, including promoting differentiation of prechondrocytes at the growth plate and stimulation of synthesis of proteins involved in IGF transport and clearance. An integrated model of interrelated role(s) of growth hormone and IGF in skeletal growth is proposed.

The effect of luteinizing hormone-releasing hormone analog for central precocious puberty on growth hormone (GH) and GH-binding protein.

The pubertal growth spurt is characterized by a marked increase in the amplitude of GH secretory pulses. The high affinity GH-binding protein (GHBP) reportedly has an important role in enhancing the growth-promoting action of GH. Levels of GHBP are characteristic for an individual and increase only slightly as puberty progresses. It has been hypothesized that each individual adjusts GH production to a level appropriate for his GHBP environment. The withdrawal of gonadal steroids that occurs in children with central precocious puberty (CPP) treated with LH-releasing hormone agonist (LHRHa) therapy results in a decrease in growth velocity (GV) and GH secretion. This study was performed to determine the effect of treatment of CPP with the LHRHa leuprolide acetate for depot suspension on GH secretion and levels of GHBP. Six girls and one boy with CPP were studied before and 6 months after treatment was initiated. Within 6 months of initiation of therapy, there was a significant decline in GV, from 8.9 +/- 3.2 to 5.4 +/- 2.0 cm/yr (P < 0.05). Twelve-hour mean nocturnal GH levels decreased significantly from 8.6 +/- 3.5 to 5.1 +/- 2.3 micrograms/L (P < 0.05). This occurred via a decrease in the amplitude of GH pulses as the number of peaks remained 4.6 and 4.1/12 h. Individual levels of GHBP were variable and reflect the wide range of levels observed in normal children. Although GV and GH levels decreased substantially, mean GHBP levels remained unchanged at 139.9 +/- 46.0 and 152 +/- 39.8 pmol/L. In children with CPP, within 6 months of LHRHa therapy, the decrease in GV occurs via a decrease in nocturnal GH secretion as levels of GHBP remain unchanged. In children with CPP, the withdrawal of gonadal steroids may inhibit the child's ability to secrete the GH appropriate for his/her GH/GHBP milieu.

Hormonal influences on in vitro [35S]-sulfate uptake by gill arches from the goldfish (Carassius auratus L.)

A bioassay for insulin-like growth factor (IGF), based on the in vitro incorporation of [(35)S]-sulfate into gill arch tissue was used to study the hormonal regulation of proteoglycan synthesis in the goldfish (Carassius auratus). [(35)S]-sulfate incorporation into gill arch tissue was found to be time-dependent with maximal uptake occurring by 48h, suggesting that proteoglycan synthesis in this tissue was maintained for at least 48h in vitro. The addition of human recombinant IGF-I (IGF-I) to the incubation medium was found to significantly stimulate [(35)S]-sulfate uptake into the gill arches, whereas bovine growth hormone (GH) was without effect. Porcine insulin was also stimulatory, but results indicate that the effects of porcine insulin and IGF-I may be mediated by a single receptor system. Finally, arches from hypophysectomized fish were significantly less responsive to IGF-I than were arches from sham-operated fish. Furthermore, administration of ovine GH in vivo appeared to increase subsequent responsiveness in vitro. Together, these results provide evidence that the growth-promoting actions of GH in the goldfish may be mediated, at least in part, by a peptide related in structure to mammalian IGF-I.

Spinal and peripheral bone mineral densities in acromegaly: the effects of excess growth hormone and hypogonadism.

To measure spinal and peripheral bone mineral densities in patients with acromegaly. Retrospective study. Tertiary care center. Twenty-four patients with acromegaly and 24 case controls. Seventeen patients (12 eugonadal and 5 hypogonadal) had "active" disease as indicated by elevated plasma concentrations of growth hormone or somatomedin C or both at the time of the study. Seven patients (all hypogonadal) had inactive disease by these criteria. Bone mineral was measured by single photon absorptiometry of the forearm and dual photon absorptiometry of the spine. The forearm bone mineral content of patients with active disease, regardless of gonadal status, was significantly higher than that of normal subjects (P less than 0.001) or of patients with inactive disease (P less than 0.001). The disease "activity" (17.2 +/- 3.7; CI, 9.5 to 24.9) and the sex of the patient (female, -16.6 +/- 3.4; CI, -23.7 to -9.5) were the only independent predictors of forearm measurements. Vertebral bone densities were lower in acromegalic patients than in normal subjects (P less than 0.001). Vertebral values were correlated with the gonadal status of the patients (hypogonadism, -0.126 +/- 0.056; CI, -0.244 to -0.009) and with serum calcium concentrations (0.592 +/- 0.274; CI, 0.032 to 1.153) but not with acromegalic activity. In 13 patients, forearm bone was measured before and after treatment (mean duration of follow-up, 3.4 years). Patients with persistently elevated, plasma somatomedin C concentrations at the end of the study period showed a mean annual increase of 1.5% in forearm measurements during the period of observation, whereas patients with normal concentrations showed a mean annual decrease of 1.0% (P less than 0.01 for the difference between the groups). The percent change in forearm bone mineral content per year (y) was highly correlated with residual somatomedin C activity (x): y = 2.023x - 2.75; r = 0.665. Forearm and vertebral bone mineral measurements change in opposite directions in acromegaly. The high forearm values are attributable to the growth-promoting action of growth hormone and somatomedin C, whereas low vertebral values are associated with hypogonadism.

Influence of age on responsiveness to diabetogenic action of growth hormone.

Responsiveness to the growth-promoting action of growth hormone (GH) develops gradually during post-natal life, and as the organism ages, sensitivity to the hormone declines. Our study was undertaken to determine whether there is a similar age-related pattern of sensitivity to the diabetogenic action of purified native human GH (hGH) in the obese (ob/ob) mouse. The ob/ob mouse was used because adults of this strain respond to chronic GH treatment with increases in fasting plasma insulin and blood glucose concentrations and with glucose intolerance. When hGH was given subcutaneously to adult (4-mo-old) female mice at doses of 5, 10, or 25 micrograms/day for 3 days, a significant increase in fasting blood glucose concentration and an impairment in glucose tolerance were produced by the 10-micrograms/day dose. Larger effects were obtained with the 25-micrograms/day dose. A threefold increase in fasting plasma insulin concentration was also produced with this dose of the hormone. By contrast, 25 micrograms/day of hGH had no effect on fasting plasma insulin, blood glucose, or glucose tolerance in 1-mo-old ob/ob mice. When a dose of 100 micrograms/day of hGH was given to 1-mo-old animals, a significant increase in fasting plasma insulin concentration occurred, but again there were no effects on fasting blood glucose or glucose tolerance. Mice 1.5 mo old showed marginal changes in fasting blood glucose and glucose tolerance when given hGH at doses of 25 or 100 micrograms/day. Mice 9 or 12 mo old exhibited responsiveness similar to that of 4-mo-old animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Some Biochemical Effects of the Growth Hormone Analogue Produced by Plerocercoids of the Tapeworm Spirometra mansonoides on Carbohydrate Metabolism of Adipose Tissue from Normal, Diabetic, and Hypophysectomized Rats

Plerocercoids of Spirometra mansonoides produce a functional analogue of mammalian growth hormone (GH). Plerocercoid growth factor (PGF) mimics the growth-promoting actions of GH, but has not been shown to duplicate all of the actions reported for GH. The purpose of this study was to determine the effects of plerocercoid infection (chronic PGF treatment) on glucose metabolism of adipose tissue and to compare the effects to those elicited by insulin and GH in intact, diabetic, and hypophysectomized male rats. Groups of rats were constantly exposed to PGF (via plerocercoid infection) or injected twice daily with bovine GH, insulin, or saline for 10 days. Basal oxidation rates of [U-14C]glucose to 14CO2 in adipose tissue segments were measured in vitro immediately after tissue removal. Other aliquots of adipose tissue were preincubated in hormone-free medium for 3 hr prior to testing the ability of the tissue to respond to insulin or human GH (hGH) added in vitro. Adipose tissue from PGF-treated intact and hypophysectomized rats had significantly elevated basal glucose oxidation rates, and the tissue was sensitive to further stimulation by insulin or hGH. The results obtained with intact and hypophysectomized rats were essentially the same, indicating that the effects of PGF were not due to suppression of endogenous GH. The basal glucose oxidation rate in adipose tissue from diabetic rats was stimulated (P less than 0.01) by PGF, but the tissue was not sensitive to insulin added in vitro. Furthermore, PGF had no effect on body growth or blood glucose concentrations of diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that somatomedin is synthesized by multiple tissues in the fetus

Production of somatomedin-C, a growth hormone-dependent peptide believed to mediate the growth-promoting actions of growth hormone, has been assessed using explants of fetal mouse tissues. Quantitation of this peptide in media of explants cultured for 3 days has been accomplished with a membrane receptor assay for somatomedin and a specific radioimmunoassay for somatomedin-C. Somatomedin-C is produced by the 11-day-gestation fetal mouse liver, increases exponentially in parallel with liver growth until the 16th day of gestation, and falls postnatally. Media somatomedin is believed to be derived by de novo synthesis since saline extracts of liver and most other fetal tissues contain only a small fraction of the activity in culture media. The immunoreactive material secreted into media appears to be closely related to human somatomedin-C since it produces dilution curves which are parallel to those of pure hormone, migrates on Sephacryl 200 at a size similar to that of one of the components of human serum somatomedin-C, dissociates into small molecular weight material with acid treatment, and isofocuses in a range comparable with that of somatomedin-C purified from human serum. Eleven-day limb bud mesenchymal micromass cultures and 17-day-gestation intestine, heart, brain, kidney, and lung also synthesize immunoreactive somatomedin-C in serum-free medium. For these tissues, the media activity was far in excess of the tissue extractable activity. Somatomedin activity in excess of the tissue extractable activity, however, was not found in media from 17-day-gestation placenta. The finding that multiple tissues synthesize somatomedin-C raises the possibility that the primary biological actions of this hormone are exerted locally at its sites of origin. Although a function of this type by a peptide has not been widely suspected, it seems plausible that the cells of fetal tissues are capable of producing local mitogens in much the same manner as the postulated inducers of tissue differentiation.

Islet cell function and glucose homeostasis in hypopituitary dwarfism: Synergism between growth hormone and cortisone

Detailed studies of islet cell function and glucose regulation were carried out in fourboys with idiopathic hypopituitary dwarfism to assess the relative importance of glucocorticoid and growth hormone deficiencies in the pathogenesis of hypoglycemia in this condition. Studies in each boy were done during a control period with no hormonal replacement and during three experimental regimens in which growth hormone alone, cortisone alone, and cortisone combined with growth hormone were administered. Combined cortisone-growth hormone therapy significantly raised blood sugar levels after overnight fasting and during fasting for prolonged periods, delayed the rate of glucose removal, decreased sensitivity to exogenous insulin, and resulted in augmentation of plasma insulin responses to intravenous administration of glucose, leucine, and tolbutamide. Thus improved islet cell function was associated with normalization of glucose homeostasis. When given separately, growth hormone and cortisone had smaller and less consistent effects. These findings are consistent with the clinical observation that treatment of hypopituitary patients with cortisone or growth hormone alone is usually ineffective in controlling hypoglycemic attacks. The synergism between cortisone and growth hormone on glucose homeostasis contrasts sharply with the antagonism of cortisone to the anabolic and growth-promoting actions of growth hormone.