Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone

1996 ◽  
Vol 135 (2) ◽  
pp. 211-215 ◽  
Author(s):  
Giuseppe Saggese ◽  
Graziano Cesaretti ◽  
Giulia Franchi ◽  
Luisa Startari

Saggese G, Cesaretti G, Franchi G, Startari L. Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone. Eur J Endocrinol 1996;135:211–5. ISSN 0804–4643 Pubertal development is associated with a rise in plasma insulin-like growth factor I (IGF-I) levels that is related both to the increase in sex steroids and/or to the sex steroid-induced augmentation in endogenous growth hormone (GH) secretion. In order to investigate the relationship between IGF-I. GH and testosterone, we examined 42 male subjects with various clinical conditions (classical GH deficiency (CGHD, N = 5), non-classical GH deficiency (NCGHD, N = 7), short idiopathic stature (N = 6), nutritional obesity (N = 8), GH-treated CGHD (N = 4), GH-treated NCGHD (N = 5) and normal stature (N = 7)) in which, for evaluation of hypogonadism (i.e. the absence of one or both testes from the scrotal sac), human chorionic gonadotropin (hCG) tests were performed. We measured IGF-I, total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassays before and 48 and 96 h after the start of the test. The values of IGF-I were lower (0.001 < p < 0.005) in CGHD and NCGHD than in the other groups. In comparison to basal levels, IGF-I values increased (0.005 < p < 0.05) both 48 and 96 h after the start of the hCG test in short idiopathic and normal stature children and in GH-treated subjects with NCGHD, but only 96 h in subjects with untreated NCGHD and GH-treated CGHD. No difference was demonstrated in basal values of total testosterone among any of the groups, while basal free testosterone levels were higher (0.001 < p < 0.05) in GH-treated subjects with NCGHD than in all the other groups except nutritional obesity; furthermore, free testosterone was higher (p < 0.05) in nutritional obesity than in CGHD. The values of total and free testosterone obtained both 48 and 96 h after the start of the hCG test were higher (0.001 < p < 0.05) than basal values in all groups. The DHEAS values did not show any significant change during the hCG test. Basal values were higher (0.01 <p < 0.05) in nutritional obesity than in the other groups. Considering all groups, chonological age, bone age and bone age/chronological age ratio were correlated with basal free testosterone, IGF-I and DHEAS levels (0.001 < p < 0.05), while basal free testosterone and IGF-I values were correlated with DHEAS levels (p < 0.005 and <0.01, respectively). In conclusion, our study during the hCG test in boys with various clinical conditions demonstrated an increase in IGF-I concentrations only in those boys with sufficient GH secretion or GH replacement therapy. These findings indicate that both sex steroids and GH are necessary to allow for the pubertal increase in IGF-I levels. Giuseppe Saggese, Endocrine Unit, Department of Pediatrics, University of Pisa, Via Rome 67, 56125 Pisa, Italy

1997 ◽  
Vol 82 (4) ◽  
pp. 1064-1070 ◽  
Author(s):  
Michael I. Lewis ◽  
Thomas J. Lorusso ◽  
Mario Fournier

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.


1994 ◽  
Vol 267 (2) ◽  
pp. E331-E336 ◽  
Author(s):  
D. A. Fryburg

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.


1994 ◽  
Vol 180 (2) ◽  
pp. 727-732 ◽  
Author(s):  
H Kimata ◽  
M Fujimoto

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.


1998 ◽  
Vol 13 (5-6) ◽  
pp. 323-326 ◽  
Author(s):  
D. Infante ◽  
R. Tormo ◽  
C. Castro de Kolster ◽  
V. Mart�nez ◽  
J. Broto ◽  
...  

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