Pulsatile growth hormone secretion in normal-weight and obese men: Differential metabolic regulation during energy restriction

Riedel, Matthias; Hoeft, Birgit; Blum, Werner; Mühlen, A. von zur; Brabant, Georg

doi:10.1016/0026-0495(95)90117-5

Cited by 70 publications

(51 citation statements)

References 37 publications

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“…On the other hand, also the existence of GHRH hypoactivity has been proposed in obesity; 8,39,40 this, in turn, could cause reduced GH synthesis and, thus, explain the reduction in the maximal secretory capacity of somatotrope cells and present data. 8,41 Other data, however, do not support the existence Figure 1 Mean ( s.e.m.)…”

Section: Discussionsupporting

confidence: 60%

“…12,13,17,18,21,23,40 Con®rm-ing the metabolic pathogenesis of GH de®ciency in obesity there is the well known evidence that spontaneous and stimulated GH secretion are restored by weight loss 2,6 and that a clear inverse relationship exists between GH secretion and body mass. 2 From a diagnostic point of view, it has to be considered that the diagnosis of GH de®ciency in adulthood is still a matter of debate though there is clear evidence for usefulness of rhGH replacement.…”

Section: Discussionmentioning

confidence: 99%

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Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

et al. 1997

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OBJECTIVE: To evaluate the maximal secretory capacity of somatotrope cells in obesity and to compare it with that in hypopituitaric patients with GH de®ciency. DESIGN: Stimulation with GHRH. (1 mg/kg iv) combined with arginine (ARG, 0.5 g/kg iv), which strongly potentiates the GH response to the neurohormone, likely inhibiting hypothalamic somatostatin. The reproducibility of the GH response to GHRH ARG was evaluated in a second session. SUBJECTS: Forty-®ve patients with simple obesity (OB 11 male and 34 female, age 40.5 AE AE 1.8 y, BMI 38.8 AE AE 1.1 kg/m 2 ), 49 patients with hypopituitarism (GHD, 23 male and 26 female, 43.6 AE AE 2.4 y, 24.7 AE AE 0.7 kg/m 2 ) and 44 normal young volunteers (NS, 25 male and 19 female, 33.8 AE AE 1.0 y, 21.6 AE AE 0.3 kg/m 2 ) were studied. MEASUREMENTS: GH levels were assayed by IRMA method, basally at 7 60 and 0 min, and than every 15 min up to 120 min. Basal IGF±I levels were assayed by RIA method, after acid-ethanol extraction. RESULTS: IGF±I levels in OB were lower (P`0.005) than those in NS but higher (P`0.005) than those in GHD. Mean peak GH response to GHRH ARG in OB was clearly lower than that in NS (P`0.005) and higher (P`0.005) than that in GHD. Sixty±percent OB and 100% GHD showed peak GH responses lower than the minimum normal limit in NS (16.5 mg/l) while 4% OB and only 53% GHD with GH responses lower than 3 mg/l, the limit under which GH replacement therapy of severe de®ciency is allowed. Good intraindividual reproducibility of the GH response to GHRH arginine test was present in all groups (OB: r 0.78, P`0.0001; GHD: r 0.57, P`0.003; NS: r 0.74, P`0.0001;. CONCLUSIONS: The maximal secretory capacity of somatotrope cells is clearly less than normal in the obese but still more than is seen in GHD subjects. However, in about 50% of obese patients, the pituitary GH releasable pool overlaps with that of hypopituitaric patients with GH de®ciency. Thus, even when the maximal secretory capacity of somatotrope cells is evaluated by a potent and reproducible provocative tests such as GHRH arginine, overweight has to be taken in a great account as the cause of severely impaired GH response in patients with suspected GH de®ciency.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

et al. 1997

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“…Short-term fasting in obesity has attenuated Effect of short fasting on GH secretion in obesity M Maccario et al inhibitory effect on insulin secretion and stimulatory effect on IGFBP-1 levels but normally increases FFA levels. It is widely accepted that starvation enhances GH secretion in humans 12,13,23 as a result of increase in GH secretory burst frequency and amplitude without any change in estimated half-life. 12,13 Prolonged (more than 3 days) fasting and caloric restriction lead to peripheral GH resistance and reduced IGF-I synthesis and release.…”

Section: Discussionmentioning

confidence: 99%

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

et al. 2001

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OBJECTIVE: Reduction of growth hormone (GH) secretion in obesity probably reflects neuroendocrine and metabolic abnormalities. Even short-term fasting stimulates GH secretion and distinguishes normal from hypopituitary subjects with growth hormone deficiency (GHD). Marked weight loss improves GH secretion in obesity but the effect of fasting is controversial. We studied the effects of a 36 h fasting on the GH=IGF-I axis and metabolic parameters in obesity. SUBJECTS: We studied nine obese patients (OB; three male and six female; age, 29.2 AE 4.8; range, 18 -59 y; body mass index (BMI), 43.4 AE 2.7 kg=m 2 ; WHR, 0.9 AE 0.1). Fifteen normal subjects (NS; eight male and seven female 28.9 AE 0.6, 25 -35 y; 21.6 AE 0.4 kg=m 2 ) and 10 adult hypopituitary patients with severe GH deficiency (GHD; seven male and three female; 37.6 AE 2.3, 29 -50 y; 24.5 AE 1.0 kg=m 2 ; GH peak < 3mg=l after ITT and=or < 9mg=l after GHRH þ arginine) served as control groups. STUDY DESIGN: We studied the effects of 36 h fasting on 8 h diurnal mean GH, insulin and glucose concentrations (mGHc, mINSc and mGLUc; assay every 30 min from 8.00 am to 4.00 pm) as well as on IGF-I, IGFBP-3, ALS, IGFBP-1, GHBP and free fatty acid (FFA) levels. RESULTS: Before fasting, basal IGF-I and ALS levels in OB were similar to those in NS and both were higher (P < 0.001) than those in GHD. IGFBP-3 levels in OB were lower (P < 0.01) than in NS but higher (P < 0.02) than in GHD. GHBP levels in OB and GHD were similar and both were higher (P < 0.01) than in NS. Glucose levels were similar in all groups. FFA levels in OB were higher (P < 0.01) than in NS but similar to those in GHD. IGFBP-1 in OB were lower (P < 0.05) than in NS and GHD which, in turn, were similar. On the other hand, mINSc in OB was higher (P < 0.01) than that in NS and GHD which, in turn, were similar. The mGHc in OB was similar to that in NS but only the latter was higher (P < 0.05) than in GHD. The individual mGHc in the three groups overlapped. After fasting, IGF-I levels in GHD were unchanged while they decreased in OB (P ¼ NS) as well as in NS (P < 0.01). IGFBP-3 and ALS levels did not change. GHBP levels in OB and GHD were unchanged while they increased in NS (P < 0.01). Glucose and FFA levels were reduced and increased, respectively, in all groups (P < 0.02 and P < 0.01). IGFBP-1 increased while mINSc decreased in all groups (P < 0.02 and P < 0.01); in OB they persisted lower and higher (P < 0.01) respectively, than in NS and GHD. Fasting significantly increased mGHc in NS (P < 0.001) but not in OB as well as in GHD. Individual mGHc in OB showed persistent overlap with GHD. CONCLUSIONS: Short-term fasting does not increase GH secretion in obesity and does not distinguish somatotroph function in obese from that in severe GHD adults. Short-term fasting in obesity has attenuated effects on insulin and IGFBP-1 secretion while it normally increases free fatty acids in spite of any change in GH secretion.

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“…However, the GH-secretory response to reduced food intake is species dependent. In humans, nutrient deprivation results in a rise in circulating GH (Ho et al 1988, Riedel et al 1995, Stoving et al 1999 accompanied by a paradoxical decrease in insulin-like growth factor (IGF)-I due to the GH resistance of peripheral target tissues (Ho et al 1992, Gianotti et al 2000. The increase in GH release is associated with an increase in pituitary sensitivity to growth hormone-releasing hormone (GHRH) and a decrease in pituitary sensitivity to somatostatin (SRIF) (Gianotti et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Fasting-induced changes in the hypothalamic-pituitary-GH axis in the absence of GH expression: lessons from the spontaneous dwarf rat

Park

Sohn²,

Kineman³

2004

Journal of Endocrinology

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Fasting results in a reciprocal shift in hypothalamic neuropeptide Y (NPY) and GH-releasing hormone (GHRH) expression in the adult male rat. It is hypothesized that the fasting-induced rise in NPY is responsible for the GHRH decline and subsequent attenuation of pulsatile GH release. Fasting also leads to a decrease in circulating IGF-I, attributed to both reduced GH release and peripheral GH resistance. Although pituitary GH output is suppressed in the fasted rat, we report herein that pituitary GHRH receptor (GHRH-R) and GH secretagogue receptor (GHS-R) mRNA levels are increased, while pituitary expression of the somatostatin receptor subtype 2 (sst2) and 5 (sst5) is decreased, as determined by real-time reverse transcription (RT)-PCR. A shift in the expression of pituitary receptor subtypes to favor GH synthesis and release may be due, at least in part, to a decline in GH/IGF-I negative feedback. In order to test this hypothesis, we compared hypothalamic and pituitary response to fasting (72 h) in normal male rats and rats with isolated GH deficiency (spontaneous dwarf rats (SDR)). Circulating GH levels were undetectable in SDR, and IGF-I levels were less than 10% of normal controls. Fasting stimulated NPY mRNA levels in SDR; however, the rise in NPY mRNA levels was not accompanied by a fall in GHRH mRNA, as observed in fasted normal rats. In fact, GHRH mRNA levels paradoxically rose in the fasted SDR to 135% of fed controls. At the pituitary level, fasting did not alter sst2 and sst5 mRNA levels in SDR but did stimulate the expression of GHRH-R and GHS-R to 165% and 149% of fed controls, respectively. These results demonstrate that the fasting-induced changes in pituitary expression of sst2 and sst5, but not GHRH-R and GHS-R, are GH/IGF-I dependent. In addition, these results argue against the theory that the negative association of NPY and GHRH expression observed following fasting represents a simple cause-and-effect relationship and suggest that GH, either directly or indirectly, mediates the effects of fasting on hypothalamic GHRH expression.

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Pulsatile growth hormone secretion in normal-weight and obese men: Differential metabolic regulation during energy restriction

Cited by 70 publications

References 37 publications

Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

Fasting-induced changes in the hypothalamic-pituitary-GH axis in the absence of GH expression: lessons from the spontaneous dwarf rat

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