Serum leptin levels during recombinant human GH therapy in adults with GH deficiency

Janssen, Y. J. H.; Frölich, Marijke; Deurenberg, P.; Roelfsema, Ferdinand

doi:10.1530/eje.0.1370650

Cited by 49 publications

(36 citation statements)

References 39 publications

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“…GH, but not insulin-like growth factor, directly inhibits leptin gene expression in visceral fat in the obese rat (30). Likewise, treatment with recombinant human GH reduces plasma leptin levels in GHdeficient patients in parallel with a fall in fat mass and a rise in lean body mass (31,32). Thus, it could be inferred that diminished GH secretion in Cushing's syndrome results in disinhibition of leptin secretion (33,34).…”

Section: Discussionmentioning

confidence: 99%

Hyperleptinemia in women with Cushing's disease is driven by high-amplitude pulsatile, but orderly and eurhythmic, leptin secretion

Veldman¹,

Frölich

Pincus

et al. 2001

European Journal of Endocrinology

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The episodicity of 24 h leptin release was studied in seven women (mean age 39 years, range 22±56 years) with pituitary-dependent hypercortisolism and in seven age-and body mass index (BMI)-matched female controls. Pulsatile leptin release was quantified by model-free CLUSTER analysis and deconvolution, the orderliness of leptin patterns by the approximate entropy statistic (ApEn), and nyctohemeral leptin rhythmicity by cosinor analysis. Blood samples were taken at 10 min intervals for 24 h. Both CLUSTER and deconvolution analysis revealed 2.4-fold increased leptin secretion in patients, caused by combined and equal amplification of basal and pulsatile secretion. Cluster analysis identified 7X1^1X5 peaks per 24 h in patients and 6X0^0X5 in controls (not significant). The statistical distribution of the individual sample secretory rates was similarly skewed in patients and controls 0X55^0X12 vs 0X52^0X07X The acrophase (timing of the nyctohemeral leptin peak) in patients occurred at 2314 h (^76 min) and at 0058 h (^18 min) in controls (not significant). The approximate entropy of leptin release was equivalent in patients and controls 1X67^0X03 vs 1X610 X05X The approximate entropy (ApEn) for cortisol in patients was 1X53^0X09 and in controls was 0X93^0X07 P , 0X0005X Cross-ApEn showed significant pattern synchrony between leptin and cortisol release, which (unexpectedly) was not disrupted by the cortisol excess (patients, 2X02^0X04; controls, 1X88^0X09; P 0X233X Insulin levels in fasting patients (`fasting insulin') were 275 X7 mUal vs 14^1X6 mUal in controls P 0X035X Leptin secretion correlated with fasting insulin levels R 2 0X34Y P 0X028 and with the cortisol production rate R 2 0X33Y P 0X033 when patients and controls were combined. In summary, Cushing's disease in women increases leptin production about twofold in an amplitude-specific way. The pulse-generating, nyctohemeral phasedetermining, and entropy-control mechanisms that govern the 24 h leptin release are not altered. The increased secretion is not explained by BMI and is probably only partly explained by increased insulin production, suggesting a cortisol-dependent change in adipose leptin secretion.

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Section: Discussionmentioning

confidence: 99%

Hyperleptinemia in women with Cushing's disease is driven by high-amplitude pulsatile, but orderly and eurhythmic, leptin secretion

Veldman¹,

Frölich

Pincus

et al. 2001

European Journal of Endocrinology

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“…Since leptin levels are strongly associated with fat mass, it can be expected that changes in plasma leptin levels will occur during treatment with GH. Most reports on GH treatment in these patients show a decrease in leptin levels, concomitant with the decreases in percentage body fat (264,269,273,274), but not independent of changes in body composition (264).…”

Section: Leptin and The Gh Axismentioning

confidence: 93%

Human leptin: from an adipocyte hormone to an endocrine mediator

2000

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Leptin is a mainly adipocyte-secreted protein that was discovered 5 years ago. Most of the research following this discovery focused on the role of leptin in body weight regulation, aiming to illuminate the pathophysiology of human obesity. However, more and more data are emerging that leptin is not only important in the regulation of food intake and energy balance, but that it also has a function as a metabolic and neuroendocrine hormone. It is now clear that it is especially involved in glucose metabolism, as well as in normal sexual maturation and reproduction. Besides this, interactions with the hypothalamic±pituitary±adrenal, thyroid and GH axes and even with haematopoiesis and the immune system have also been described. It has been shown that leptin secretion by the adipocyte is partly regulated by other hormones, such as insulin, cortisol, and sex steroids, mainly testosterone. Also, other hormones like thyroid hormone and GH are possibly involved in leptin synthesis. Leptin itself exerts effects on different endocrine axes, mainly on the hypothalamic±pituitary±gonadal axis and on insulin metabolism, but also on the hypothalamic±pituitary±adrenal, thyroid and GH axes.Leptin may thus be considered a new endocrine mediator, besides its obvious role in body weight regulation.

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“…With both testosterone as well as growth hormone treatment these variables improve (8,13,14). Testosterone administration to hypogonadal men improves bone density and muscle mass and decreases adipose tissue (4, 9, 15 -18).…”

Section: Introductionmentioning

confidence: 99%

Testosterone substitution of hypogonadal men prevents the age-dependent increases in body mass index, body fat and leptin seen in healthy ageing men: results of a cross-sectional study

Claus¹,

Eckardstein²,

Koken³

et al. 2002

European Journal of Endocrinology

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Introduction: In healthy men, body weight and total fat content increase with advancing age, while serum testosterone levels decrease. In order to elucidate whether a causal relationship between these phenomena exists, we investigated the influence of testosterone or human chorionic gonadotrophin substitution on body mass index (BMI), total fat mass and serum leptin in testosterone-treated and untreated hypogonadal patients in comparison with ageing eugonadal men. Methods: In a cross-sectional study, the inter-relationships of body weight, total fat mass, serum sex hormones and leptin were analysed in untreated hypogonadal men (n ¼ 24; age 19-65 years), treated hypogonadal men (n ¼ 61; age 20-67 years) and healthy eugonadal men (n ¼ 60; age 24-78 years). Total fat mass was assessed by bioimpedance measurement. Univariate and multiple linear regression analysis was used to detect possible differences. Results: In eugonadal men, serum testosterone levels decreased with advancing age (correlation coefficents: r ¼ 20:71; P , 0:0001), while BMI ðr ¼ 0:39; P ¼ 0:002Þ; total fat content ðr ¼ 0:51; P , 0:0001Þ and leptin ðr ¼ 0:48; P , 0:0001Þ increased significantly. In untreated hypogonadal patients, an increase in BMI ðr ¼ 0:50; P ¼ 0:013Þ and total fat mass ðr ¼ 0:41; P ¼ 0:044Þ was also observed with advancing age. However, in substituted hypogonadal patients, no age-dependent change in BMI ðr ¼ 0:067; P ¼ 0:606Þ; body fat content ðr ¼ 20:083; P ¼ 0:522Þ; serum testosterone ðr ¼ 20; 071; P ¼ 0:59Þ or serum leptin ðr ¼ 20:23; P ¼ 0:176Þ was found. Conclusion: Since testosterone-substituted older hypogonadal men show BMI and fat mass similar to those of younger eugonadal men and since non-treated hypogonadal men are similar to normal ageing men, testosterone appears to be an important factor contributing to these changes. Thus ageing men should benefit from testosterone substitution as far as body composition is concerned.

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Serum leptin levels during recombinant human GH therapy in adults with GH deficiency

Cited by 49 publications

References 39 publications

Hyperleptinemia in women with Cushing's disease is driven by high-amplitude pulsatile, but orderly and eurhythmic, leptin secretion

Hyperleptinemia in women with Cushing's disease is driven by high-amplitude pulsatile, but orderly and eurhythmic, leptin secretion

Human leptin: from an adipocyte hormone to an endocrine mediator

Testosterone substitution of hypogonadal men prevents the age-dependent increases in body mass index, body fat and leptin seen in healthy ageing men: results of a cross-sectional study

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