Glucocorticoid (Gc) -Induced Growth Stunting and Therapeutic Possibilities With Growth Hormone (Gh) and/or Insulin-Like Growth Factor-I (Igf-I) 42

Lewis, Michael I., Thomas J. LoRusso, and Mario Fournier.Effect of insulin-like growth factor I and/or growth hormone on diaphragm of malnourished adolescent rats. J. Appl. Physiol. 82(4): 1064–1070, 1997.—Young growing animals appear to have significantly reduced “nutritional reserve” to short periods of unstressed starvation compared with adults, with resultant growth arrest and/or atrophy of diaphragm (Dia) muscle fibers. The aim of this study was to assess in an adolescent rat model of acute nutritional deprivation (ND; 72 h) the impact of insulin-like growth factor I (IGF-I), with or without added growth hormone (GH), on the cross-sectional areas (CSA) of individual Dia muscle fibers. Five groups were studied: 1) control (Ctr); 2) ND; 3) ND given IGF-I (ND/IGF-I); 4) ND given GH (ND/GH); and 5) ND given a combination of IGF-I and GH (ND/IGF-I/GH). IGF-I was given by a subcutaneously implanted osmotic minipump (200 μg/day), whereas GH was administered twice daily by a subcutaneous injection (250 μg every 12 h). Isometric contractile and fatigue properties of the Dia were determined in vitro. Forces were normalized for muscle CSA (i.e., specific force). Dia fiber type proportions were determined histochemically, and fiber CSA was quantified by using a computer-based image-processing system. Total serum IGF-I concentrations were significantly reduced in ND and ND/GH animals, compared with Ctr, and elevated in the groups receiving IGF-I. The provision of growth factors did not alter the contractile or fatigue properties of ND animals. Dia fiber type proportions were similar among the groups. In ND animals, there was a significant reduction in the CSA of types I, IIa, IIx, and IIc Dia fibers compared with Ctr. The administration of IGF-I alone or in combination with GH to ND animals significantly diminished the reduction in Dia fiber size. GH alone had no effect on Dia fiber size in ND animals. We conclude that with acute ND the peripheral resistance to the action of GH appears to be bypassed by the administration of IGF-I alone or in combination with GH.

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Insulin-like growth factor I exerts growth hormone- and insulin-like actions on human muscle protein metabolism

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.2.e331 ◽

1994 ◽

Vol 267 (2) ◽

pp. E331-E336 ◽

Cited By ~ 21

Author(s):

D. A. Fryburg

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Muscle Protein ◽

Muscle Metabolism ◽

Insulin Like Growth Factor ◽

Factor I ◽

Igf I ◽

Muscle Protein Metabolism ◽

Growth Factor I ◽

Forearm Muscle

The effect of a 6-h intra-arterial infusion of recombinant human (rh) insulin-like growth factor I (IGF-I) on forearm muscle metabolism was studied in 19 postabsorptive subjects. Forearm glucose, lactate, and phenylalanine (Phe) balances, as well as estimates of protein degradation (Phe Ra) and synthesis (Phe Rd) were measured before and at 3 and 6 h into an infusion of rhIGF-I at a dose of 1.8 (n = 6), 6.0 (n = 8), or 10.0 (n = 5) micrograms.kg-1.h-1. In response to intra-arterial IGF-I, deep venous IGF-I rose by 55, 141, and 315%, respectively (all P < 0.01), and forearm blood flow accelerated by 75 (1.8 microgram), 213 (6.0 micrograms), and 159% (10.0 micrograms; all P < 0.02). No change in forearm glucose uptake was observed at the lowest dose, whereas four- to sixfold increases were observed at both the 6 and 10 micrograms.kg-1.h-1 doses (both P < 0.02). Forearm Phe balance shifted positively at all three doses by 27 +/- 6, 48 +/- 7, and 51 +/- 9 nmol.min-1 x 100 ml-1, respectively (all P < 0.01). At all three doses, Phe Rd increased comparably by 49-74% (all P < 0.05). At the 6.0 and 10.0 but not the 1.8 microgram.kg-1.h-1 dose, Phe Ra decreased by approximately 45% (P < 0.02). Forearm muscle metabolism was also studied in the contralateral non-IGF-infused arm at these three doses. Despite increases in deep venous IGF-I up to 517 ng/ml due to recirculating IGF-I (10.0 micrograms.kg-1.h-1 dose), contralateral forearm muscle glucose, lactate, or Phe handling did not change. In conclusion, intra-arterial IGF-I exhibits growth hormone-like effects at all doses tested, whereas the insulin-like effects are observed at higher doses; these effects appear dependent on the route of administration.

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Growth hormone and insulin-like growth factor I induce immunoglobulin (Ig)E and IgG4 production by human B cells.

Journal of Experimental Medicine ◽

10.1084/jem.180.2.727 ◽

1994 ◽

Vol 180 (2) ◽

pp. 727-732 ◽

Cited By ~ 38

Author(s):

H Kimata ◽

M Fujimoto

Keyword(s):

Growth Hormone ◽

B Cells ◽

Growth Factor ◽

Mononuclear Cells ◽

Immunoglobulin E ◽

Interleukin 4 ◽

Insulin Like Growth Factor ◽

Factor I ◽

Igf I ◽

Growth Factor I

We studied the effects of growth hormone (GH), insulin-like growth factor I (IGF-I), IGF-II, and insulin on human immunoglobulin E (IgE) and IgG4 production. GH and IGF-I induced IgE and IgG4 production by normal donors' mononuclear cells (MNC) depleted of sIgE+ and sIgG4+ B cells without affecting IgM, IgG1, IgG2, IgG3, IgA1, or IgA2 production, whereas IGF-II and insulin failed to do so. GH-induced IgE and IgG4 production was specific, and was not mediated by IGF-I, interleukin 4 (IL-4), or IL-13, since it was blocked by anti-GH antibody (Ab), but not by anti-IGF-I Ab, anti-IL-4 Ab, or anti-IL-13 Ab. Conversely, IGF-I-induced IgE and IgG4 production was blocked by anti-IGF-I Ab, but not by anti-GH Ab, anti-IL-4 Ab, or anti-IL-13 Ab. Moreover, interferon alpha (IFN-alpha) or IFN-gamma, which counteracted IL-4-and IL-13-induced IgE and IgG4 production, had no effect on induction by GH or IGF-I. In contrast to MNC, GH or IGF-I failed to induce IgE and IgG4 production by purified sIgE-, sIgG4- B cells. However, in the presence of anti-CD40 monoclonal antibody (mAb), GH or IGF-I induced IgE and IgG4 production by these cells. Purified sIgE+, but not sIgE-, B cells from atopic patients spontaneously produced IgE. GH or IGF-I with anti-CD40 mAb failed to enhance IgE production by sIgE+ B cells, whereas they induced IgE production by sIgE- B cells. Similarly, whereas GH or IGF-I with anti-CD40 mAb failed to enhance IgG4 production by sIgG4+ B cells from atopic patients, they induced IgG4 production by sIgG4- B cells. Again, neither IgE nor IgG4 induction was blocked by anti-IL-4 Ab or anti-IL-13 Ab. These results indicate that GH and IGF-I induce IgE and IgG4 production by class switching in an IL-4- and IL-13-independent mechanism.

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