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Research Notes: Growth Hormone PhysiologyDomest Anim Endocrinol. 2007 Sep 11. In this study the hypothesis that irreversible glucose loss results in an 'uncoupling' of the somatotrophic axis (increasing plasma GH levels and decreasing plasma IGF-I) was tested. During periods of negative energy balance the somatotrophic axis respond by increasing plasma GH and decreasing plasma IGF-I levels. In turn, elevated GH repartitions nutrient by increasing lipolysis and protein synthesis, and decreases protein degradation. Irreversible glucose loss was induced using sub-cutaneous injections of phloridizin. Seven non-lactating cows were treated with 8g/day phloridizin (PHZ) and seven control animals (CTRL, 0g/day), while being restricted to a diet of 80% maintenance. PHZ treatment increased urinary glucose excretion (P<0.001), resulting in hypoglycemia (P<0.001). As a response to this glucose loss, the PHZ treated animals had elevated plasma NEFA (P<0.005) and BHBA (P<0.001) levels. Average plasma insulin concentrations were not altered with PHZ treatment (P=0.059). Plasma GH was not different between the two groups (P>0.1), whereas plasma IGF-I levels decreased significantly (P<0.001) with PHZ treatment. The decline in plasma IGF-I concentrations was mirrored by a decrease in the abundance of hepatic IGF-I mRNA (P=0.005), in addition the abundance of hepatic mRNA for both growth hormone receptors (GHR(tot) and GHR(1A)) was also decreased (P<0.05). Therefore, the irreversible glucose loss resulted in a partial 'uncoupling' of the somatotrophic axis, as no increase in plasma GH levels occurred although plasma IGF-I levels, hepatic IGF-I mRNA declined, and the abundance of liver GH receptor mRNA declined. Am J Physiol Endocrinol Metab. 2007 Jul. Muscle is a target of growth hormone (GH) action and a major contributor to whole body metabolism. Little is known about how GH regulates metabolic processes in muscle or the extent to which muscle contributes to changes in whole body substrate metabolism during GH treatment. To identify GH-responsive genes that regulate substrate metabolism in muscle, we studied six hypopituitary men who underwent whole body metabolic measurement and skeletal muscle biopsies before and after 2 wk of GH treatment (0.5 mg/day). Transcript profiles of four subjects were analyzed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF-I) and procollagens I and III were measured by RIA. GH increased serum IGF-I and procollagens I and III, enhanced whole body lipid oxidation, reduced carbohydrate oxidation, and stimulated protein synthesis. It induced gene expression of IGF-I and collagens in muscle. GH reduced expression of several enzymes regulating lipid oxidation and energy production. It reduced calpain 3, increased ribosomal protein L38 expression, and displayed mixed effects on genes encoding myofibrillar proteins. It increased expression of circadian gene CLOCK, and reduced that of PERIOD. In summary, GH exerted concordant effects on muscle expression and blood levels of IGF-I and collagens. It induced changes in genes regulating protein metabolism in parallel with a whole body anabolic effect. The discordance between muscle gene expression profiles and metabolic responses suggests that muscle is unlikely to contribute to GH-induced stimulation of whole body energy and lipid metabolism. GH may regulate circadian function in skeletal muscle by modulating circadian gene expression with possible metabolic consequences. Glia. 2007 Jun 18. Proinflammatory cytokine-mediated injury to oligodendrocyte progenitor cells (OPCs) has been proposed as a cause of periventricular leukomalacia (PVL), the most common brain injury found in preterm infants. Preventing death of OPCs is a potential strategy to prevent or treat PVL. In the current study, we utilized an in vitro cell culture system to investigate the effect of insulin-like growth factor-1 (IGF-1) on tumor necrosis factor-alpha (TNFalpha)-induced OPC injury and the possible mechanisms involved. OPCs were isolated from neonatal rat optic nerves and cultured in chemically defined medium (CDM) supplemented with platelet-derived growth factor and basic fibroblast growth factor. Exposure to TNFalpha resulted in death of OPCs. IGF-1 protected OPCs from TNFalpha cytotoxicity in a dose-dependent manner as measured by the XTT and TUNEL assays. IGF-1 activates both the PI3K/Akt and the extracellular signal-regulated kinase (ERK) pathway. However, IGF-1-enhanced cell survival signals were mediated by the PI3K/Akt, but not by the ERK pathway, as evidenced by the observation that IGF-1-enhanced cell survival was partially abrogated by Akti, the Akt inhibitor, or wortmannin, the PI3K inhibitor, but not by PD98059, the MAPK kinase/ERK kinase inhibitor. The downstream events of IGF-1-triggered survival signals included phosphorylation of BAD, blockade of TNFalpha-induced translocation of Bax from the cytosol to the mitochondrial membrane, and suppression of caspase-9 and caspase-3 activation. These observations indicate that the protection of OPCs by IGF-1 is mediated, at least partially, by interruption of the mitochondrial apoptotic pathway via activation of PI3K/Akt. J Clin Densitom. 2007 Apr 28. The aim of our study was to evaluate the effects of long-life severe growth hormone deficiency on bone mineral density (BMD) and bone scintigraphy in adult patients with childhood onset (CO) hypopituitarism never treated with growth hormone. Our studies included 22 adult patients with CO hypopituitarism never treated with growth hormone (13 males and 9 females, aged 25-66yr). The patients received replacement therapy with thyroxine, sex steroid hormones, and patients with secondary adrenocortical deficiency, hydrocortisone, but none of the patients had ever received GH treatment. In 22 patients, the total body with regional distribution of BMD, the lumbar spine L2-L4, and radial (33% site) BMD were determined by dual energy X-ray absorptiometry (DXA). In addition, 12 patients had the femoral neck BMD examined. In 10 cases, bone scintigraphy using 99-technetium labeled methylene diphosphonate was performed. Our studies revealed abnormalities, not yet described, in the regional distribution of BMD and bone scintigraphy in adults with CO hypopituitarism never treated with GH. In all patients, the results obtained from the total body showed definite disproportion in the regional distribution of BMD with a significantly advanced bone mineral deficit in the legs and a moderate deficit in the arms and total body. Local BMD measured at the radial (33% site) and lumbar spine L2-L4 revealed also a more pronounced bone mineral deficit in the cortical bone (33% distal radius) than in the trabecular bone (spine L2-L4). Bone scintigraphy showed a decrease in tracer accumulation in the shafts of the long bones but normal uptake in the spine, ribs, sternum, skull, and periarticular areas, indicating suppressed skeletal metabolism of cortical bone. Our studies indicate that long-life growth hormone deficiency leads to deficient and abnormal distribution of bone mineralization, a more pronounced deficit of BMD at the cortical bone, mainly expressed in the shafts of the long bones of the legs and arms, and moderately reduced BMD at the trabecular bone. Bone scans displaying low diphosphonates uptake in the shafts of the long bones point to greatly suppressed skeletal metabolism of the cortical bone in the patients with CO hypopituitarism never treated with GH. Clin Endocrinol (Oxf). 2007 Apr. The growth hormone-insulin-like growth factor 1 (GH-IGF-1) axis plays an important role in modulating the peripheral metabolism of glucocorticoids mainly through its effect on the isoenzyme 11 beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) which, in vivo, functions as a reductase catalysing the conversion of cortisone to cortisol. Several in vivo and ex vivo studies have shown that the GH-IGF-I system inhibits the expression and activity of 11beta-HSD1 in adipose tissues and the liver resulting in reduced local regeneration of cortisol. This interaction has clinically significant implications as it may at least partly explain the phenotypes of acromegaly and adult GH deficiency and the effects that treatment of these conditions has on body composition. In addition, by accelerating the peripheral metabolism of cortisol, GH therapy may precipitate adrenal insufficiency in susceptible hypopituitary patients, and endocrinologists should be mindful of this phenomenon when starting hypopituitary patients on GH replacement therapy. Gastroenterology. 2007 Mar. BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is an emerging progressive hepatic disease and demonstrates steatosis, inflammation, and fibrosis. Insulin resistance is a common feature in the development of NASH. Molecular pathogenesis of NASH consists of 2 steps: triglyceride accumulation in hepatocytes with insulin resistance and an enhanced oxidative stress caused by reactive oxygen species. Interestingly, NASH demonstrates a striking similarity to the pathologic conditions observed in adult growth hormone deficiency (AGHD). AGHD is characterized by decreased lean body mass, increased visceral adiposity, abnormal lipid profile, and insulin resistance. Moreover, liver dysfunctions with hyperlipidemia and nonalcoholic fatty liver disease (NAFLD) are frequently observed in patients with AGHD, and it is accompanied by metabolic syndrome. METHODS: We studied a case diagnosed as NASH with hyperlipidemia in AGHD. The effect of GH-replacement therapy on the patient was analyzed. RESULTS: Six months of GH-replacement therapy in the patient drastically ameliorated NASH and the abnormal lipid profile concomitant with a marked reduction in oxidative stress. CONCLUSIONS: These results suggest that GH plays an essential role in the metabolic and redox regulation in the liver. Diabetes Obes Metab. 2007 Jan. Growth hormone (GH) is generally considered to exert anti-insulin actions, whereas insulin-like growth factor I (IGF-I) has insulin-like properties. Paradoxically, GH deficient adults and those with acromegaly are both predisposed to insulin resistance, but one cannot extrapolate from these pathological conditions to determine the normal metabolic roles of GH and IGF-I on glucose homeostasis. High doses of GH treatment have major effects on lipolysis, which plays a crucial role in promoting its anti-insulin effects, whereas IGF-I acts as an insulin sensitizer that does not exert any direct effect on lipolysis or lipogenesis. Under physiological conditions, the insulin-sensitizing effect of IGF-I is only evident after feeding when the bioavailability of circulating IGF-I is increased. In contrast, many studies in GH deficient adults have consistently shown that GH replacement improves the body composition profile although these studies differ considerably in terms of age, the presence or absence of multiple pituitary hormone deficiency, and whether GH deficiency was childhood or adult-onset. However, the improvement in body composition does not necessarily translate into improvements in insulin sensitivity presumably due to the anti-insulin effects of high doses of GH therapy. More recently, we have found that a very low dose GH therapy (0.1 mg/day) improved insulin sensitivity without affecting body composition in GH-deficient adults and in subjects with metabolic syndrome, and we postulate that these effects are mediated by its ability to increase free 'bioavailable' IGF-I without the induction of lipolysis. These results raise the possibility that this low GH dose may play a role in preventing the decline of beta-cell function and the development of type 2 diabetes in these "high risk" subjects. Zhonghua Jie He He Hu Xi Za Zhi. 2006 Apr. Objective: To explore the regulation of hypothalamus-pituitary-adrenal (HPA) axis and growth hormone (GH) axis in obstructive sleep apnea-hypopnea syndrome (OSAHS). Methods: OSAHS patients (OSAHS group) and subjects with obesity alone (control group) were monitored by polysomnography (PSG). The corticotropin-releasing hormone (CRH), growth hormone releasing hormone (GHRH), corticotropin (ACTH), cortisol and growth hormone levels in plasma were measured by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay before and after sleep. Their correlation were analyzed. Results: The CRH concentration [(1.66 +/- 0.34), (4.96 +/- 0.98) mmol/L before and after sleep] and cortisol content [(152.93 +/- 136.15), (445.53 +/- 123.09) microg/L before and after sleep] in the OSAHS group were significantly higher than those of the control group [CRH was (0.67 +/- 0.42), (2.27 +/- 1.10) mmol/L, cortisol concentration was (68.94 +/- 20.13), (146.05 +/- 30.48) microg/L, before and after sleep, respectively, all P < 0.01]; GHRH significantly decreased in the OSAHS group [(1.42 +/- 0.07), (1.01 +/- 0.05) mmol/L before and after sleep] compared with the control group [(1.99 +/- 0.34), (1.58 +/- 0.15) mmol/L, respectively; all P < 0.01]; but there was no difference in growth hormone. The ratio of the variation of CRH, GHRH level (DeltaCRH/DeltaGHRH) was significantly higher in the OSAHS group (285.02 +/- 143.32) than that in the control group (71.15 +/- 15.37, P < 0.01). The bivariate correlation analysis of the OSAHS group indicated that DeltaCRH/DeltaGHRH was correlated positively with average awake duration (r = 0.882), but negatively with average blood oxygen concentration (r = -0.696). The average blood oxygen concentration was negatively correlated with average awake duration (r = -0.729). Conclusions: There are abnormal changes of HPA axis and GH axis in OSAHS patients, and the feedback regulation is disordered. These abnormalities are related to sleep structure variation and hypoxia during sleep. Horm Metab Res. 2005 Dec. Background: Growth hormone (GH) treatment in patients with GH deficiency (GHD) can determine changes in the thyroid function. The clinical significance of these changes remains controversial, and all studies have so far covered rather a short period - usually no longer than one year. Objective: To determine the effect of long-term recombinant hGH treatment in children with idiopathic GHD on the thyroid function. Patients and methods: Nineteen prepubertal children (12 boys and 7 girls, mean age 9.2 +/- 3.1 years) with idiopathic GHD were studied and followed for twenty-four months. None of the patients showed multiple pituitary hormone deficiencies. Nineteen healthy children matched for age and sex acted as controls. Results: Patients with GHD showed a significant increase in TT (3) at twelve months and in FT (3) at six and twelve months after starting GH treatment, with a significant decrease at eighteen and twenty-four months. TT (4) level decreased significantly at twelve months and increased significantly at eighteen and twenty-four months. FT (4) also decreased, but only slightly, after twelve months of hGH treatment, and then increased significantly at twenty-four months. TSH levels did not vary significantly during the course of therapy. TT (3)/TT (4) and FT (3)/FT (4) ratios increased significantly after six and twelve months of therapy and significantly decreased later, approaching pre-therapy values. The SDS of Growth Velocity (SDS-GV) increased remarkably during the first year of therapy and then decreased significantly during the second year, although it remained significantly higher than the pre-therapy values. TT (3) and TT (3)/TT (4) ratio displayed a significant correlation with SDS-GV at twelve months of therapy. In a multiple regression analysis with age, bone age, parental height, GH dose, TT (3,) TT (3)/TT (4), and the SDS of IGF-I, only the TT (3)/TT (4) ratio at twelve months of therapy (p < 0.001) was identified as a significant predictor of SDS-GV. Conclusion: Our data confirm that changes in thyroid function are present in GHD children during long-term hGH therapy. These changes probably resulted from the effect of hGH on the peripheral metabolism of thyroid hormones and appear to be transitory, disappearing during the second year of hGH treatment. We speculate on the functional significance of these changes, and in particular, on their role in catch-up growth after hGH therapy. J Clin Endocrinol Metab. 2003 Apr. The effects of GH replacement therapy on energy metabolism are still uncertain, and long-term benefits of increased muscle mass are thought to outweigh short-term negative metabolic effects. This study was designed to address this issue by examining both short-term (1 wk) and long-term (6 months) effects of a low-dose (9.6 micro g/kg body weight.d) GH replacement therapy or placebo on whole-body glucose and lipid metabolism (oral glucose tolerance test and euglycemic hyperinsulinemic clamp combined with indirect calorimetry and infusion of 3-[(3)H]glucose) and on muscle composition and muscle enzymes/metabolites, as determined from biopsies obtained at the end of the clamp in 19 GH-deficient adult subjects. GH therapy resulted in impaired insulin-stimulated glucose uptake at 1 wk (-52%; P = 0.008) and 6 months (-39%; P = 0.008), which correlated with deterioration of glucose tolerance (r = -0.481; P = 0.003). The decrease in glucose uptake was associated with an increase in lipid oxidation at 1 wk (60%; P = 0.008) and 6 months (60%; P = 0.008) and a concomitant decrease in glucose oxidation. The deterioration of glucose metabolism during GH therapy also correlated with the enhanced rate of lipid oxidation (r = -0.508; P = 0.0002). In addition, there was a shift toward more glycolytic type II fibers during GH therapy. In conclusion, replacement therapy with a low-dose GH in GH-deficient adult subjects is associated with a sustained deterioration of glucose metabolism as a consequence of the lipolytic effect of GH, resulting in enhanced oxidation of lipid substrates. Also, a shift toward more insulin-resistant type II X fibers is seen in muscle. Glucose metabolism should be carefully monitored during long-term GH replacement therapy. Med Hypotheses. 2001 May. A new technique for controllable elevation of night time growth hormone (GH) release in adult humans involves a synergy between oral intake of the naturally occurring compounds acetyl-L-carnitine (500 mg) and L-ornithine (25-100 mg) taken at night time sleep after a 3 to 4 hour fast. The set point for normal hypothalamic GH release appears to include a 'whole body' mitochondrial State 3 status 'feed back loop' controlled by systemic acetyl-L-carnitine levels. J Pediatr Endocrinol Metab. 2000 Sep. Physiological effects of growth hormone (GH) extend beyond the stimulation of linear growth. These include important metabolic effects upon adipose tissue. GH affects both proliferation and differentiation of preadipocytes, although this varies between clonal cell lines and preadipocyte cultures. Both preadipocytes and mature adipocytes possess specific GH receptors. GH may mediate its actions via these receptors, but some effects are indirectly mediated through the GH-mediated secretion of insulin-like growth factor-I (IGF-I) within adipose tissue. GH promotes lipolysis via inhibition of lipoprotein lipase, which hydrolyzes triglycerides in the circulation to make them available for triglyceride accumulation in adipose tissue. GH also stimulates hormone sensitive lipase (HSL), the rate-limiting step for release of stored triglyceride in adipocytes (lipolysis). As GH becomes utilized for various "non-growth" concerns (see Figure 1), awareness of the metabolic effects on adipocytes is important to understand the clinical effects seen with GH therapy. J Clin Endocrinol Metab. 2000 Apr. We examined the effects of recombinant human (rh) insulin-like growth factor I (IGF-I) vs. rhGH in a variety of metabolic paths in a group of eight severely GH-deficient young adults using an array of contemporary tools. Protein, glucose, and calcium metabolism were studied using stable labeled tracer infusions of L-[1-13C]leucine, [6,6-2H2]glucose, and 42Ca and 44Ca; substrate oxidation rates were assessed using indirect calorimetry; muscle strength was determined by isokinetic and isometric dynamometry of the anterior quadriceps, as well as growth factors, hormones, glucose, and lipid concentrations in plasma before and after 8 weeks of rhIGF-I (60 microg/kg, sc, twice daily), followed by 4 weeks of washout, then 8 weeks ofrhGH (12.5 microg/kg-day, sc); the treatment order was randomized. In the doses administered, rhIGF-I and rhGH both increased fat-free mass and decreased the percent fat mass, with a more robust decrease in the percent fat mass after rhGH; both were associated with an increase in whole body protein synthesis rates and a decrease in protein oxidation. Neither hormone affected isokinetic or isometric measures of skeletal muscle strength. However, rhGH was more potent than rhIGF-I at increasing lipid oxidation rates and improving plasma lipid profiles. Both hormones increased hepatic glucose output, but rhGH treatment was also associated with decreased carbohydrate oxidation and increased glucose and insulin concentrations, indicating subtle insulin resistance. Neither hormone significantly affected bone calcium fluxes, supporting the concept that these hormones, by themselves, are not pivotal in bone calcium metabolism. In conclusion, rhIGF-I and rhGH share common effects on protein, muscle, and calcium metabolism, yet have divergent effects on lipid and carbohydrate metabolism in the GH-deficient state. These differences may allow for better selection of treatment modalities depending on the choice of desired effects in hypopituitarism. Endocr Rev. 1996 Oct. It is very clear that the GH-IGF axis plays a major role in controlling the growth and differentiation of skeletal muscles, as it does virtually all of the tissues in the animal body. One aspect of this control is unquestioned: circulating GH acts on the liver to stimulate expression of the IGF-I and IGFBP3 genes, substantially increasing the levels of these proteins in the circulation. It also seems that GH stimulates expression of IGF-I genes in skeletal muscle, although there are a number of cases in which skeletal muscle IGF-I expression is elevated in the absence of GH. It is substantially less clear that GH acts directly on skeletal muscle to stimulate its growth; the presence of GH receptor mRNA in skeletal muscle is well established, but most investigators have been unsuccessful in demonstrating any specific binding of GH to skeletal muscle or to myoblasts in culture. It has been equally difficult to show direct actions of GH on cultured muscle cells; the only positive report concludes that the early insulin-like effects of GH can result from direct interactions between GH and isolated muscle cells. The effects of the IGFs on skeletal muscle are much clearer. It is well established by studies in a number of laboratories on a variety of systems that IGFs stimulate many anabolic responses in myoblasts, as they do in other cell types. IGFs have the unusual property of stimulating both proliferation and differentiation of myoblasts, responses that are generally believed to be mutually exclusive; in myoblasts, they are in fact temporally separated. The stimulation of differentiation by IGF-I is (at least in part) a result of substantially increased levels of the mRNA for myogenin, the member of the MyoD family most directly associated with terminal myogenesis. As levels of myogenin mRNA rise, those of myf-5 mRNA (the only other member of the MyoD family expressed significantly in L6 myoblasts) fall dramatically, although myf-5 expression is required for the initial elevation of myogenin. The effects of IGFs are significantly modulated by IGFBPs secreted by myoblasts in serum-free medium, inhibitory IG-FBPs-4 and -6 are expressed and secreted by L6A1 myoblasts, while expression of IGFBP-5 rises dramatically as differentiation proceeds. Other myoblasts also secrete IGFBP-2. Even if exogenous IGFs are not added to the low-serum "differentiation" medium, myoblasts express sufficient amounts of autocrine IGF-II to stimulate myogenesis after a period of time; some myogenic cell lines, (such as Sol 8) are so active in expressing the IGF-II gene that it is not possible to demonstrate effects of exogenous IGFs. This autocrine expression of IGFs is by no means unique to skeletal muscle cells; indeed, it is so widely seen in cells responding to mitogenic stimuli that we suggest that IGFs can be viewed as extracellular second messengers that mediate most, if not all, such actions of agents that stimulate cell proliferation. The component of serum that suppresses IGF-II gene expression under "growth" conditions appears to be the IGFs themselves, which exhibit a very high potency in the feedback inhibition of IGF-II expression. In addition, IGFs have effects on the expression of other genes related to differentiation. Treatment of L6A1 cell with IGFs suppresses their expression of the myogenesis-inhibiting TGF beta s with a time course consistent with an initial proliferative step followed by differentiation, i.e. expression is first increased and then very substantially decreased. It is not established that this plays a role in control of differentiation, but experiments with FGF antisense constructs suggests that this may well be the case. Until recently, IGFs were the only circulating agents known to stimulate myoblast differentiation, in contrast to the relatively large number of growth factors that inhibit the process. It is now clear that thyroid hormones and RA also stimulate myogenesis... Metabolism. 1996 Aug. The role of growth hormone (GH) and thyroid hormone in the regulation of lipid and lipoprotein metabolism is not fully established. Furthermore, the possible linkage between the well-known GH-induced increase in peripheral thyroxine (T4) to triiodothyronine (T3) generation and the effects of GH on lipid and lipoprotein metabolism has not been elucidated. In this double-blind placebo-controlled study, we compared the effects of GH and T3 administration alone and in combination on lipid and lipoprotein metabolism in a group of healthy young adults. The dose of T3 was selected to mimic the T2 increase seen during exogenous GH exposure. Eight normal male subjects (aged 21 to 27 years; body mass index, 21.11 to 27.17 kg/m2) were randomly studied during four 10-day treatment periods with (1) daily subcutaneous placebo injections and placebo injections and placebo tablets, (2) daily subcutaneous GH injections (0.1 IU/kg.d) and placebo tablets, (3) daily T3 administration (40 micrograms on even dates or 20 micrograms on uneven dates) plus placebo injections, and (4) daily GH injections plus T3 administration. GH administration increased free T3 (FT3) to the same level as during T3 administration. GH caused decreased levels of total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol and increased levels of triglycerides (TG) and lipoprotein(a) (Lp(a)), but no changes in high-density lipoprotein (HDL) cholesterol and apolipoprotein B (apo B). T3 administration caused no alteration in these parameters, except for decreased levels of TC comparable to those seen after GH administration. Combined GH and T3 administration caused changes identical to those seen after GH administration, in addition to decreased apo B levels and a further decrease of TC levels. We conclude that GH and iodothyronines in the physiologic range exert distinct but disparate effects on lipids and lipoproteins, and do not support the hypothesis that the effects observed during GH administration are exclusively secondary to changes in peripheral T3 levels. Eur J Endocrinol. 1996 May. Insulin-like growth factor I (IGF-I) is considered to mediate some of the growth-promoting and metabolic effects of growth hormone (GH). Growth hormone treatment of healthy and GH-deficient subjects is accompanied by increased conversion of thyroxine (T4) to triiodothyronine (T3) in peripheral tissues. Whether these effects are mediated by IGF-I is unknown. To assess the respective roles of these hormones on thyroid hormone metabolism we have treated two groups of subjects. The first group consisted of eight healthy subjects who were treated with IGF-I (10 micrograms.kg-1.h-1 sc for 5 days). The second group consisted of eight subjects with combined GH and thyrotropin (TSH) deficiency due to acquired pituitary disease. They were treated with IGF-I (10 micrograms.kg-1.h-1 sc for 7 days), GH (2 IU m-2 sc q.i.d.) or both hormones together. The IGF-I treatment in healthy subjects led to an increase in free T3 (FT3) and a reduction in TSH levels, whereas FT4 and total T4 (TT4) levels remained unchanged. In the second group-in which all subjects were substituted with oral L-thyroxine-treatment with IGF-I led to an elevation of FT3 in the face of unchanged T4 levels. Growth hormone alone and GH plus IGF-I resulted in a more pronounced elevation in T3 level. The results suggest that IGF-I partially mediates the well-known effects of GH on peripheral conversion of T4 to T3. However, GH has more pronounced effects on thyroid hormones that apparently are not mediated by IGF-I. |