Effects of GH replacement on metabolism and physical performance in GH deficient adults

Shakoor, Sadaf; Shalet, Stephen M

doi:10.1007/bf03345243

Cited by 21 publications

(14 citation statements)

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“…Adult patients with growth hormone deficiency are predisposed to premature atherosclerosis and other cardiovascular diseases (Twickler et al, 2000;Elhadd et al, 2001). Growth hormone replacement in GH-deficient adult patients improves their LDL-cholesterol abnormalities (Twickler et al, 2000;Abdul Shakoor and Shalet, 2003). Therefore, growth hormone also prevents atherosclerosis and other cardiovascular diseases.…”

Section: Discussionmentioning

confidence: 99%

Hormonal and Chemical Regulation of Paraoxonases in Mice

Cheng

Klaassen

2012

J Pharmacol Exp Ther

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In humans and rodents, paraoxonase (PON/Pon) 1 expression and activity in livers and serum are higher in females than in males, and some drugs increase paraoxonase's expression. However, the underlining mechanisms of gender-divergent expression and chemical regulation of Pon1 remain largely unknown. The present study determined the regulatory mechanisms contributing to gender-divergent and chemically altered Pon expression in mouse livers. Pon1 mRNA was much more abundant in the livers of mice than other tissues, with higher levels in female livers than male livers at mRNA and protein levels. Pon2 mRNA was ubiquitously expressed in mouse tissues, but minimally in mouse liver. Pon3 mRNA was most abundant in mouse lung and liver and less abundant in other tissues. Pon1 mRNA was lowest in fetal liver, markedly increased at parturition, and remained relatively constant thereafter. Pon2 and Pon3 mRNA are highly expressed in fetal liver and decreased after birth. Male-pattern growth hormone (GH) administration in hypophysectomized and lit/lit mice decreased Pon1 expression. Sex hormones and female-pattern GH administration had no effect on Pon1 expression, indicating the importance of male-pattern GH in regulating Pon1. Aryl hydrocarbon receptor, pregnane X receptor, and NF-E2-related factor activators had no effect on Pon1 mRNA. A constitutive androstane receptor (CAR) activator decreased Pon1 expression in wild-type but not CAR-null mice. In conclusion, Pon1 mRNA was most abundant in adult mouse livers, whereas Pon2 and Pon3 mRNAs were most abundant in fetal mouse livers. Female-predominant Pon1 expression in mouse livers is caused by the inhibitory effects of male-pattern GH secretion, and CAR activation decreases Pon1 expression.

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Section: Discussionmentioning

confidence: 99%

Hormonal and Chemical Regulation of Paraoxonases in Mice

Cheng

Klaassen

2012

J Pharmacol Exp Ther

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“…In acromegalic patients, excess GH does not result in increased muscle mass or strength (21)(22)(23), while the observed increase in muscle strength and endurance experienced by GHD patients following GH treatment appear to be a result of altered metabolic functions as well as a stimulation of protein synthesis, suppression of protein oxidation and increased muscle mass (24)(25)(26)(27). Taken together, it is currently not clear whether GH/IGF1 and skeletal muscle myofibrillar protein synthesis are positively correlated in man, but investigating both acromegalic and GHD patients offers a unique possibility to address this question.…”

Section: Introductionmentioning

confidence: 97%

GH and IGF1 levels are positively associated with musculotendinous collagen expression: experiments in acromegalic and GH deficiency patients

Doessing¹,

Holm²,

Heinemeier³

et al. 2010

European Journal of Endocrinology

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Objective: Disproportionate growth of musculoskeletal tissue is a major cause of morbidity in both acromegalic (ACRO) and GH-deficient (GHD) patients. GH/IGF1 is likely to play an important role in the regulation of tendon and muscle collagen. We hypothesized that the local production of collagen is associated with the level of GH/IGF1. Design and methods: As primary outcomes, collagen mRNA expression and collagen protein fractional synthesis rate (FSR) were determined locally in skeletal muscle and tendon in nine ACRO and nine GHD patients. Moreover, muscle myofibrillar protein synthesis and tendon collagen morphology were determined. Results and conclusions: Muscle collagen I and III mRNA expression was higher in ACRO patients versus GHD patients (P!0.05), whereas collagen protein FSR did not differ significantly between ACRO and GHD patients in muscle (PZ0.21) and tendon (PZ0.15). IGF1Ea and IGF1Ec mRNA expression in muscle was higher in ACRO patients versus GHD patients (P!0.01). Muscle IGF1Ea mRNA expression correlated positively with collagen I mRNA expression (P!0.01). Tendon collagen fibrillar area tended to be higher in GHD patients relative to ACRO patients (PZ0.07). Thus, we observed a higher expression for collagen and IGF1 mRNA in local musculotendinous tissue in ACRO patients relative to GHD patients. Moreover, there was a tendency towards a higher collagen protein FSR and a smaller collagen fibril diameter in ACRO patients relative to GHD patients. The results indicate a collagenstimulating role of local IGF1 in human connective tissue and add to the understanding of musculoskeletal pathology in patients with either high or low GH/IGF1 axis activity.

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“…GH has important physiological functions in adult humans and several studies have shown that GHD in adult patients is associated with abnormalities in body composition, visceral obesity, metabolic derangements and impaired physical performance (2 -7). These impairments improve with recombinant human GHreplacement therapy (rhGH) (2,4,6,(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index

et al. 2005

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Objective: The diagnosis of growth hormone (GH) deficiency (GHD) in adults is based on a reduced peak GH response to provocative tests, such as the insulin tolerance test (ITT) and the GH-releasing hormone-arginine (GHRH-ARG) test. However, the cut-off limits of peak GH response in lean subjects are not reliable in obese patients; this is noteworthy since adult GHD is often associated with obesity. Aim of this study was to evaluate the diagnostic cut-off limits of peak GH response to the GHRH-ARG test in overweight and obese as well as in lean population. Design and methods: The GH responses to the GHRH-ARG test were studied in 322 patients with organic hypothalamic-pituitary disease and in 318 control subjects. Patients were subdivided into two groups on the basis of the number of pituitary hormone deficits, except for GH deficiency: (a) patients with total pituitary hormone deficit (TPHD) and (b) patients without or with no more than two pituitary hormone deficits (PHD). Both patients and control subjects were divided into three subgroups according to body mass index (BMI): lean (BMI , 25 kg/m 2 ), overweight (BMI $ 25 and , 30 kg/m 2 ) and obese (BMI $30 kg/m 2 ). TPHD patients were assumed to be GH deficient, whereas PHD patients may include subjects with either normal or impaired GH secretion. The statistical analysis was carried out by the Receiver-Operating Characteristic curve analysis (Medcalc 7.2). The diagnostic cut-off points were calculated for lean, overweight and obese subjects to provide optimal separation of GH-deficient patients and control subjects according to two criteria: (1) a balance between high sensitivity and high specificity; (2) to provide the highest pair of sensitivity/specificity values for GH deficiency. Results: In the lean population the best pair of values, with highest sensitivity as 98.7% and highest specificity as 83.7%, was found using a peak GH cut-off point of 11.5 mg/l. In the overweight population the best pair of values, 96.7 and 75.5%, respectively, was found using a peak GH cut-off point of 8.0 mg/l. In the obese population the best pair of values, 93.5 and 78.3%, respectively, was found using a peak GH cut-off point of 4.2 mg/l. Applying the above mentioned cut-off points, among PHD patients we found that 80 subjects (72%) were GHD whereas 31 (28%) had normal GH secretion. Conclusions: In conclusion the GHRH-ARG test is a reliable tool for the diagnosis of adult GH deficiency in lean, overweight and obese patients, provided that specific BMI-related cut-off limits are assumed.European Journal of Endocrinology 153 257-264

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Effects of GH replacement on metabolism and physical performance in GH deficient adults

Cited by 21 publications

References 58 publications

Hormonal and Chemical Regulation of Paraoxonases in Mice

Hormonal and Chemical Regulation of Paraoxonases in Mice

GH and IGF1 levels are positively associated with musculotendinous collagen expression: experiments in acromegalic and GH deficiency patients

The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index

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