Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Spontaneous and Growth Hormone (GH)-Releasing Hormone-Stimulated GH Secretion in Anorexia Nervosa

Gianotti, L.

doi:10.1210/jc.85.8.2805

Cited by 17 publications

(17 citation statements)

References 21 publications

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“…Reportedly, GH secretion is increased in the florid phase of the disease, and, although this has been related to a loss of the feedback action of circulating IGF-I (Berelowitz et al 1981, Counts et al 1992, Ross & Chew 1995, Gianotti et al 2000, a primary hyperfunction of GHRH-secreting neurons cannot be disregarded (Scacchi et al 1997, Stoving et al 1999a, 1999b, Gianotti et al 2000, Pincelli et al 2002. If this were the case, one cannot rule out the possibility that GHRH-secreting neurons are, in turn, under an enhanced stimulation by hypothalamic ghrelin-secreting neurons (Hewson & Dickson 2000).…”

Section: Discussionmentioning

confidence: 99%

Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients

Rigamonti¹,

Pincelli²,

Corra³

et al. 2002

Journal of Endocrinology

266

135

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Ghrelin, a novel endogenous ligand for the GH secretagogue receptor, has been reported to stimulate GH secretion and food intake in both humans and other animals. Interestingly, recent data indicate that ghrelin is up-and down-regulated in anorexia nervosa (AN) and obesity, which are also known to be accompanied by increased and reduced GH levels respectively. Ageing is associated with a gradual but progressive reduction in GH secretion, and by alterations in appetite and food intake. The role of ghrelin in the decline of somatotroph function and the anorexia of ageing is unknown.To investigate the influence of age on circulating levels of ghrelin, a total of 19 young and old normal weight subjects (Y-NW, n=12; O-NW, n=7), six patients with active AN (A-AN), and seven patients with morbid obesity (OB) were studied. In addition to fasting plasma ghrelin concentrations, baseline serum TSH, IGF-I and insulin levels were measured.Mean plasma ghrelin concentrations in A-AN or OB were higher and lower respectively than those present in Y-NW. Interestingly, mean plasma ghrelin concentrations in O-NW were significantly lower than those present in Y-NW and superimposable on those of OB. The mean fasting plasma ghrelin concentrations in all groups of subjects were negatively correlated with body mass index and serum insulin levels, but not with TSH and IGF-I levels.This study provides evidence of an age-related decline of plasma ghrelin concentrations, which might explain, at least partially, the somatotroph dysregulation and the anorexia of the elderly subject.

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Section: Discussionmentioning

confidence: 99%

Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients

Rigamonti¹,

Pincelli²,

Corra³

et al. 2002

Journal of Endocrinology

266

135

View full text Add to dashboard Cite

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“…One possible mechanism could involve the reduced IGF-I levels produced by malnutrition. Gianotti et al (61) showed that a low IGF-I dose inhibits, though does not normalize, spontaneous and stimulated GH secretion in patients with AN. These findings indicate the existence of a defective hypothalamic control of GH release (61).…”

Section: Gh -Igf-i Axismentioning

confidence: 99%

“…Gianotti et al (61) showed that a low IGF-I dose inhibits, though does not normalize, spontaneous and stimulated GH secretion in patients with AN. These findings indicate the existence of a defective hypothalamic control of GH release (61). This would effect a reduction in the negative feedback action that IGF-I exerts on GH secretion at the level of both the hypothalamus and the pituitary (60).…”

Section: Gh -Igf-i Axismentioning

confidence: 99%

Anorexia nervosa in female adolescents: endocrine and bone mineral density disturbances

Argente

2002

European Journal of Endocrinology

146

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Anorexia nervosa (AN) is a chronic childhood psychiatric illness that involves a reduction in caloric intake, loss of weight and amenorrhea, either primary or secondary. The diagnostic criteria for AN have been established by the American Psychiatric Association. The prevalence of this disease amongst adolescents and young adults is between 0.5 and 1% and the incidence of new cases per year is approximately 5-10/100 000 between 15 and 19 years of age. A number of endocrine and metabolic disturbances have been described in patients with AN including amenorrhea-oligomenorrhea, delayed puberty, hypothyroidism, hypercortisolism, IGF-I deficiency, electrolyte abnormalities, hypoglycemia and hypophosphatemia, among others. In addition to prolonged amenorrhea, osteopenia and osteoporosis are the most frequent complications leading to clinically relevant fractures and increased fracture risk throughout life. Patients exhibit an alteration in the hypothalamic -pituitary -gonadal axis, which is responsible for the menstrual disorders. The increase in gonadotropin secretion that can be observed after ponderal recuperation suggests that malnutrition could be the most important mechanism involved in the decrease in gonadotropin secretion. The loss of fat tissue as a consequence of nutrient restriction has been associated with hypoleptinemia and abnormal secretion of peptides implicated in food control (neuropeptide Y, melanocortins and corticotropin-releasing factor, among others). A review of the endocrine abnormalities, disturbances in neurotransmitters, as well as a detailed analysis of bone markers and bone mineral density in patients with AN is described.

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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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Effects of Recombinant Human Insulin-Like Growth Factor I Administration on Spontaneous and Growth Hormone (GH)-Releasing Hormone-Stimulated GH Secretion in Anorexia Nervosa

Cited by 17 publications

References 21 publications

Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients

Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients

Anorexia nervosa in female adolescents: endocrine and bone mineral density disturbances

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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