Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by growth hormone in rat white adipose tissue.

Peter, M.; Winterhalter, Kaspar H.; Böni-Schnetzler, Marianne; Froesch, E. R.; Zapf, J.

doi:10.1210/endo.133.6.7694843

Cited by 53 publications

(25 citation statements)

References 38 publications

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“…This probably indicates a fast turnover rate of the IGF-I in the infused animals caused by the lack of IGF binding proteins (IGFBPs) and, therefore, a short half-life of IGF-I. It is known that GH is an essential stimulator of acid-labile subunit (ALS) synthesis [25] as well as IGFBP-3, IGFBP-5 [26,27] and formation of the 150-kilodalton ternary IGF-I-IGFBP-3, (or IGFBP-5)-ALS complex will not occur in the absence of GH, greatly reducing the half-life of IGF-I [28,29]. It had previously been demonstrated using both the SDRs [29] and hypophysectomized rats [28] that IGF-I administration only partially restores the circulating levels of IGF-I and normal body weight gain is only acquired in the presence of GH, and it has now been categorically demonstrated using the IGF-I and GH receptor (GHR) double knockout mouse model that both IGF-I and GH are required for normal body growth [30].…”

Section: Discussionmentioning

confidence: 99%

Mammary tumorigenesis in growth hormone deficient spontaneous dwarf rats; effects of hormonal treatments

Thórdarson¹,

Semaan²,

Low³

et al. 2004

Breast Cancer Res Treat

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This study was carried out to investigate mammary tumorigenesis in growth hormone (GH) deficient spontaneous dwarf rats (SDR). At 50-60 days of age, the rats were divided into five groups. Group 1 received bovine (b) GH (prolonged release formulation) administered at a dose of 40-50 mg/kg body wt. in 50 microl weekly injections; group 2 received recombinant human insulin-like growth factor-I (IGF-I) at a dose of 1 mg/kg body wt./day administered via osmotic pumps; animals in group 3 were fitted with subcutaneous silastic capsule containing 30 microg 17 beta-estradiol (E2) plus 30 mg progesterone (P4), replaced every 2 months; group 4 received both bGH and E2 plus P4 treatments at the same doses as above, and control animals (group 5) received sham treatments (vegetable oil injection, silastic capsules containing cellulose). After 1 week of treatment, all animals were injected intraperitoneally with the carcinogen N-methyl-N-nitrosourea (MNU) at a dose of 50 mg/kg body wt. Other groups of animals, receiving identical hormonal treatment to those exposed to MNU, were treated for 10 days only and then sacrificed for assessment of circulating concentrations of hormones and mammary gland characteristics at the time of carcinogen exposure. The hormonal treatments of the animals exposed to the MNU were continued for an additional 20 weeks and mammary tumor development monitored by weekly palpation and tumors collected as necessary. The rats were weighed weekly. At the end of the treatment period, all animals were sacrificed and remaining tumors were collected. Rats in all groups continued to gain weight throughout the experimental period, but the largest weight gain was see in animals receiving GH either alone or with E2 and P4. Animals treated with IGF-I also gained weight compared to controls, but this weight gain was less than that seen in GH-treated rats. GH treatment alone increased mammary tumor incidence from 4.8% in controls to 100%. Average tumor load and latency in the GH-treated rats were 7.0 +/- 0.8 tumors/tumor-bearing rat (mean +/- SEM) and 57.3 +/- 2.7 days (mean +/- SEM), respectively. As in intact Sprague-Dawley rats, approximately 90% of the tumors that developed in the GH-treated rats were ovarian dependent for growth. IGF-I treatment also increased mammary tumor development to 62.5%. Average tumor load and latency in the IGF-I-treated rats were 1.6 +/- 0.4 tumors/tumor-bearing rat (mean +/- SEM) and 96.2 +/- 14.5 days (mean +/- SEM), respectively. However E2 + P4 treatments did not significantly alter tumorigenesis and, surprisingly, simultaneous treatment with E2 + P4 and GH obliterated the GH-stimulated increase in tumor development. Prolactin (PRL) did not appear to influence mammary tumorigenesis in the SDRs, as untreated SDRs had significantly elevated serum concentration of PRL as compared with normal Sprague-Dawley (SD) rats, whereas GH-treated SDRs had PRL levels similar to that of normal SD rats. No obvious structural characteristics were associated with high or low susceptibility to mammary ...

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Section: Discussionmentioning

confidence: 99%

Mammary tumorigenesis in growth hormone deficient spontaneous dwarf rats; effects of hormonal treatments

Thórdarson¹,

Semaan²,

Low³

et al. 2004

Breast Cancer Res Treat

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“…STAT5A and STAT5B bind to the ALS-GAS1 in response to GH and mediate transcriptional activation of the ALS gene (Ooi et al, 1997). Although it is well-recognized that GH stimulates IGF-1 production and gene expression in liver and other cell types (Bichell et al, 1992;Isgaard et al, 1988;Mathews et al, 1986;Peter et al, 1993), identifying the GH-regulated transcription factors involved has been challenging. Establishment of novel GH-responsive cell lines has facilitated demonstration that STAT5 participates in GH-stimulated expression of IGF-1.…”

Section: Stat5 Involvement In the Expression Of Serine Protease Inhibmentioning

confidence: 99%

The role of STAT proteins in growth hormone signaling

et al. 2000

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Growth hormone (GH) has long been known to be the body's primary regulator of body growth and a regulator of metabolism, yet the mechanisms by which GH regulates the transcription of speci®c genes required for these processes are just now being delineated. GH binding to its receptor recruits and activates the receptor-associated JAK2 that in turn phosphorylates tyrosines within itself and the GH receptor. These tyrosines form binding sites for a number of signaling proteins, including members of the family of signal transducers and activators of transcription (STAT). Among the known signaling molecules for GH, STAT proteins play a particularly prominent role in the regulation of gene transcription. This paper will review what is currently understood about which STAT proteins are regulated by GH, how they are regulated by GH, the GH-dependent genes they regulate, and discuss current theories about how GH-activated STAT signaling is regulated. Particular attention will be given to the novel role that STAT5 plays in sexually dimorphic gene expression in the liver as determined by the secretory pattern of GH and the role of STAT5 in body growth.

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“…The demonstration that IGF-I mRNA levels in adipose tissue are similar to those found in the liver [72], known to be the major source of circulating IGF-I, has led to the hypothesis that adipose tissue could be a major contributor of circulating IGF-I levels in obesity (fig. 1).…”

Section: Gh-igf-i Axis and Ghbp/gh Receptor In Obesitymentioning

confidence: 99%

“…Hypophysectomy results in a marked decrease in IGF-I mRNA in rat adipose tissues. GH replacement almost completely restored IGF-I mRNA level and normalized the IGF-I level in this tissue [72, 73]. Although GH hyposecretion in obesity may cause a decrease in the generation of IGF-I in each adipocyte, significantly greater amounts of IGF-I could be secreted from the accumulated adipose tissues in obesity than from other tissues on a tissue weight basis [75].…”

Section: Gh-igf-i Axis and Ghbp/gh Receptor In Obesitymentioning

confidence: 99%

“…In the human, both the exon-3-retaining and exon-3-deleting isoforms of the GH receptor are expressed [80]. Hypophysectomy has been demonstrated to decrease adipose tissue GH receptor gene expression in the rat, and GH replacement restores receptor expression towards normal [72, 85]. Similarly in the human, treatment of Prader-Willi syndrome or GH-deficient patients with GH results in an upregulation of adipose tissue GH receptor gene expression [86].…”

Section: Effect Of Gh On Adipocytesmentioning

confidence: 99%

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Growth Hormone and Adipocyte Function in Obesity

Nam

Marcus

2000

Horm Res Paediatr

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In obesity, growth hormone (GH) secretion is impaired which is considered a consequence rather than a cause of obesity. GH regulates the expression of GH receptor and the synthesis of insulin-like growth factor I (IGF-I) in adipocytes. Although GH hyposecretion in obesity may decrease the generation of IGF-I in each adipocyte, increased amounts of IGF-I and GH-binding protein could be secreted from the excessively enlarged amounts of adipose tissue. This may contribute to the normal/high serum-IGF-I and high GH-binding protein levels in obesity. Hyperinsulinemia and increased GH receptor activity may also affect the GH-IGF-I axis. Favorable effects of GH treatment have been observed in obese children and adults. GH treatment decreases adiposity, reduces triglyceride accumulation by inhibiting lipoprotein lipase and enhances lipolysis both via increased hormone-sensitive lipase activity and via induction of beta adrenoreceptors. GH treatment also has a favorable effect on obesity-associated dyslipidemia, but the effects on insulin sensitivity have been conflicting.

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Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by growth hormone in rat white adipose tissue.

Cited by 53 publications

References 38 publications

Mammary tumorigenesis in growth hormone deficient spontaneous dwarf rats; effects of hormonal treatments

Mammary tumorigenesis in growth hormone deficient spontaneous dwarf rats; effects of hormonal treatments

The role of STAT proteins in growth hormone signaling

Growth Hormone and Adipocyte Function in Obesity

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