Serum IGF-I Is Not a Reliable Pharmacodynamic Marker of Exogenous Growth Hormone Activity in Mice

Bielohuby, Maximilian; Schaab, Michael; Kummann, Moritz; Sawitzky, Mandy; Gebhardt, Rolf; Binder, Gerhard; Frystyk, Jan; Bjerre, Mette; Hoeflich, Andreas; Kratzsch, Juergen; Bidlingmaier, Martin

doi:10.1210/en.2011-1432

Cited by 22 publications

(21 citation statements)

References 44 publications

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“…These authors had also observed the persistency of high IGF1 levels at adulthood in that GH-overexpression model (Mt-bGH mice) and concluded animals were already maximally stimulated. More recently, IGF1 has been reported not to be a predictable marker of GH function in mice (Bielohuby, et al 2011), which may account for the lack of correlation we found between basal STAT5 phosphorylation levels and IGF1 induction in adult animals.…”

Section: Discussioncontrasting

confidence: 54%

GH/STAT5 signaling during the growth period in livers of mice overexpressing GH

Martínez¹,

Piazza²,

Díaz³

et al. 2015

Journal of Molecular Endocrinology

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Growth hormone (GH)/STAT5 signaling is desensitized in liver of adult transgenic mice overexpressing GH; however, these animals present greater body size. To assess if the STAT5 pathway is active during the growth period in liver of these animals, and how signaling modulators participate in this process, growing transgenic mice and normal siblings were evaluated. STAT5 does not respond to an acute GH-stimulus but presents higher basal phosphorylation in liver of growing GH-overexpressing mice. GH receptor and positive modulators GR and HNF1 display greater abundance in transgenic animals, supporting STAT5 activity. Negative modulators CIS and PTP1B are increased in GH-overexpressing mice. Suppressors SOCS2 and SOCS3 exhibit higher mRNA levels in transgenic mice but lower protein content, suggesting they are being actively degraded. Therefore, STAT5 signaling is increased in liver of GH-transgenic mice during the growth period, with a balance between positive and negative effectors resulting in an accelerated but controlled growth.

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Section: Discussioncontrasting

confidence: 54%

GH/STAT5 signaling during the growth period in livers of mice overexpressing GH

Martínez¹,

Piazza²,

Díaz³

et al. 2015

Journal of Molecular Endocrinology

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“…This limited the statistical analysis to a Cox regression and, consequently, the small increase in IGF‐1 as a result of GH injection was not detected as being significant. The response of IGF‐1 to GH injection was poor, although it has previously been noted that IGF‐1 may not be a reliable pharmacodynamic marker of exogenous GH treatment in rodents . The increase in body mass was contributed to by an increase in both liver and kidney mass for GH‐treated hamsters.…”

Section: Discussionmentioning

confidence: 94%

Somatostatin Agonist Pasireotide Promotes a Physiological State Resembling Short‐Day Acclimation in the Photoperiodic Male Siberian Hamster (Phodopus sungorus)

Dumbell

Scherbarth²,

Diedrich³

et al. 2015

J Neuroendocrinology

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The timing of growth in seasonal mammals is inextricably linked to food availability. This is exemplified in the Siberian hamster (Phodopus sungorus), which uses the annual cycle of photoperiod to optimally programme energy expenditure in anticipation of seasonal fluctuations in food resources. During the autumn, energy expenditure is progressively minimised by physiological adaptations, including a 30% reduction in body mass, comprising a reduction in both fat and lean tissues. However, the mechanistic basis of this adaptation is still unexplained. We hypothesised that growth hormone (GH) was a likely candidate to underpin these reversible changes in body mass. Administration of pasireotide, a long-acting somatostatin receptor agonist developed for the treatment of acromegaly, to male hamsters under a long-day (LD) photoperiod produced a body weight loss. This comprised a reduction in lean and fat mass, including kidneys, testes and brown adipose tissue, typically found in short-day (SD) housed hamsters. Furthermore, when administered to hamsters switched from SD to LD, pasireotide retarded the body weight increase compared to vehicle-treated hamsters. Pasireotide did not alter photoperiod-mediated changes in hypothalamic energy balance gene expression but altered the expression of Srif mRNA expression in the periventricular nucleus and Ghrh mRNA expression in the arcuate nucleus consistent with a reduction in GH feedback and concurrent with reduced serum insulin-like growth factor-1. Conversely, GH treatment of SD hamsters increased body mass, which included increased mass of liver and kidneys. Together, these data indicate a role for the GH axis in the determination of seasonal body mass of the Siberian hamster.

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“…Thirdly, some of the effects of GH on the brain are probably mediated by peripheral circulating IGF1 (for review, see Å berg et al (2006)). As circulating IGF1 levels are much more even and regulated by the cumulative effect of GH stimulation over 1-2 days (Bielohuby et al 2011), the pulsatility of GH injections may be partially attenuated. Specifically, it appears that there are two major transport systems of IGF1 across the BBB.…”

Section: Effects Of Gh Administration With Respect To Plasticity and mentioning

confidence: 99%

Different modes of GH administration influence gene expression in the male rat brain

Walser

Schiöler

Oscarsson

et al. 2014

Journal of Endocrinology

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The endogenous secretion pattern in males of GH is episodic in rats and in humans, whereas GH administration is usually even. Different types of GH administration have different effects on body mass, longitudinal bone growth, and liver metabolism in rodents, whereas possible effects on brain plasticity have not been investigated. In this study, GH was administered as a continuous infusion or as two daily injections in hypophysectomized male rats. Thirteen transcripts previously known to respond to GH in the hippocampus and parietal cortex (cortex) were assessed by RT-PCR. To investigate the effects of type of GH administration on several transcripts with different variations, and categories of transcripts (neuron-, glia-, and GH-related), a mixed model analysis was applied. Accordingly, GH injections increased overall transcript abundance more than GH infusions (21% in the hippocampus, P!0.001 and 10% in the cortex, PZ0.09). Specifically, GH infusions and injections robustly increased neuronal hemoglobin beta (Hbb) expression significantly (1.8-to 3.6-fold), and GH injections were more effective than GH infusions in increasing Hbb in the cortex (41%, PZ0.02), whereas a 23% difference in the hippocampus was not significant. Also cortical connexin 43 was higher in the group with GH injections than in those with GH infusions (26%, P!0.007). Also, there were differences between GH injections and infusions in GH-related transcripts of the cortex (23%, PZ0.04) and glia-related transcripts of the hippocampus (15%, PZ0.02). Thus, with the exception of Hbb there is a moderate difference in responsiveness to different modes of GH administration.

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Serum IGF-I Is Not a Reliable Pharmacodynamic Marker of Exogenous Growth Hormone Activity in Mice

Cited by 22 publications

References 44 publications

GH/STAT5 signaling during the growth period in livers of mice overexpressing GH

GH/STAT5 signaling during the growth period in livers of mice overexpressing GH

Somatostatin Agonist Pasireotide Promotes a Physiological State Resembling Short‐Day Acclimation in the Photoperiodic Male Siberian Hamster (Phodopus sungorus)

Different modes of GH administration influence gene expression in the male rat brain

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