Consequences of postnatally elevated insulin-like growth factor-II in transgenic mice: endocrine changes and effects on body and organ growth.

Wolf, Eckhard; Kramer, Rainer; Blum, Werner; Föll, Jürgen; Brem, Gottfried

doi:10.1210/endo.135.5.7525257

Cited by 83 publications

(39 citation statements)

References 39 publications

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“…Also IGF2 seems to have specific effects for adrenal growth and function. Although body weight was not significantly affected in mice overexpressing IGF2, the adrenal glands in these transgenic mice showed significant increases in weight ( Wolf et al 1994, Weber et al 1999. In summary, several components of the GH/IGF1 system potently influence growth and function of the mouse adrenal gland.…”

Section: Gh/igfmentioning

confidence: 86%

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

Hoeflich¹,

Bielohuby²

2008

Journal of Molecular Endocrinology

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The adrenal gland influences a multitude of processes during stress response, but also potently affects the immune system, glucose metabolism, electrolyte or water homeostasis, and cardiovascular functions. According to the present understanding, the adrenal cortex is tightly controlled by the hypothalamic-pituitary-adrenal axis. This axis involves hypothalamic CRH and pituitary ACTH which determine processes of adrenocortical growth and function. However, control of the adrenal gland comprises a plethora of additional endogenous or exogenous factors. Among those are diverse hormones, psychosocial parameters, physiological stress, secondary plant products, or even environmental pollutants. In the present review, we summarize the current view of endocrine growth control in the adrenal gland. We then discuss intracellular mechanisms of adrenal growth control and focus on extracellular signal regulated kinases 1/2 ( ERK1/2), which have been demonstrated to be controlled by not only ACTH or angiotensin II, but also by a large number of additional effectors. On the basis of these multiple exogenous or endogenous factors which impact on the adrenal gland through ERK1/2 activity, we speculate on a mechanism by which ERK1/2 act as a central integrative growth regulatory elements in the adrenal gland.

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Section: Gh/igfmentioning

confidence: 86%

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

Hoeflich¹,

Bielohuby²

2008

Journal of Molecular Endocrinology

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“…Furthermore, adult IGF-II serum levels are very high (700 ng/ml), and the biologically active fraction that is not bound to IGFBPs might be large enough to exert an endocrine effect in the adrenal gland (Humbel 1990). An endocrine effect of elevated levels of IGF-II on the adrenal gland has recently been suggested by the findings of Wolf et al (1994), who reported an increased adrenal weight in transgenic mice that develop elevated serum levels of IGF-II postnatally (Wolf et al 1994). Adult bovine and human adrenocortical cells therefore represent a useful model system to help us to investigate the complex interaction of two IGF ligands, two IGF receptors, six IGFBPs and at least as many IGFBP-specific proteases.…”

Section: Discussionmentioning

confidence: 99%

Regulation of steroidogenesis by insulin-like growth factors (IGFs) in adult human adrenocortical cells: IGF-I and, more potently, IGF-II preferentially enhance androgen biosynthesis through interaction with the IGF-I receptor and IGF-binding proteins

Fottner¹,

Engelhardt²,

Weber³

1998

Journal of Endocrinology

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Although the effect of insulin-like growth factors (IGFs) in fetal adrenocortical cells has been investigated extensively, the role of the IGF system in the adult human adrenal gland remains unclear. In the present study we investigated the effect of recombinant human IGF-I and IGF-II on cortisol, dehydroepiandrosterone sulfate (DHEA-S) and cAMP synthesis in adult human adrenocortical cells in primary culture. Both IGFs stimulate basal as well as adrenocorticotropin (ACTH)-induced steroid secretion in a time-and dose-dependent fashion. While both IGFs (6·5 nM) induced only a moderate 2-fold increase in basal cortisol output after 48 h, the effect on basal DHEA-S secretion was significantly stronger, with a 2·7-and 3·7-fold stimulation by IGF-I and IGF-II respectively. Similarly, IGF-II enhanced ACTH-induced cortisol and DHEA-S secretion more potently than IGF-I. In doseresponse experiments, the maximum stimulation of ACTH-induced DHEA-S secretion was induced by 1·6 nM IGF-I (2-fold increase) or IGF-II (2·9-fold increase), while the maximum response of cortisol secretion was elicited only at 13 nM IGF-I (2-fold increase) or IGF-II (2·5-fold increase). This resulted in a significant shift of the DHEA-S dose-response curves to the left, indicating a relative selective stimulation of androgen biosynthesis by physiologically low concentrations (0·4-3·2 nM) of IGF-II, and less potently by IGF-I. At all doses tested, the steroidogenic effect of IGF-II was significantly stronger than the effect of IGF-I. Although both IGF receptors are present in adult human adrenocortical cells, the steroidogenic effect of IGF-II is mediated through the IGF-I receptor, since [Arg 54,55 ]IGF-II, which only binds to the IGF-I receptor, was equipotent with native IGF-II, whereas [Leu 27 ]IGF-II, which preferentially binds to the type II IGF receptor, did not show any effect. In addition, [des 1-3 ]IGF-I, which exhibits only minimal binding to IGFBPs, was significantly more potent than native IGF-I in stimulating adrenal steroid biosynthesis, and elicited almost the same maximum stimulatory effect as IGF-II and [des [1][2][3][4][5][6] ]IGF-II. By Western ligand blotting of conditioned medium it was shown that adult human adrenocortical cells secrete various IGF-binding proteins (IGFBPs), which are induced differentially by treatment with ACTH. In conclusion, these results demonstrate that: (1) IGF-II stimulates basal as well as ACTH-induced DHEA-S and cortisol secretion from adult human adrenocortical cells more potently than IGF-I; (2) both IGFs predominantly stimulate androgen biosynthesis; (3) the steroidogenic effect of IGF-I and IGF-II is mediated through interaction with the IGF-I receptor; (4) the different steroidogenic potency of IGF-I and IGF-II might be explained by interaction of these ligands with locally produced IGFBPs. These data indicate that the IGF system plays an important role in the regulation of the differentiated function of adult human adrenocortical cells.

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“…While GH-over-expressing mice exhibit increased kidney size and hypertrophy [27], IGF-I over-expression results in hyperplasia [28] and increased glomerular size [27,29] indicative of distinct effects of GH and IGF-I on kidney growth or development. IGF-II over-expression also results in an overall increase in kidney size [30,31]. IGF-I-deficient animals display particular muscle hypoplasia [24], and IGF-I excess results in skeletal muscle hypertrophy [32].…”

Section: The Gh-igf-i Axis In Modulating Growth and Organ Developmentmentioning

confidence: 99%

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

Mak

Cheung

Roberts

2008

Growth Hormone & IGF Research

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Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are important physiologic regulators of growth, body composition, and kidney function. Perturbations in the GH-IGF-I axis are responsible for many important complications seen in chronic kidney disease (CKD), such as growth retardation and cachectic wasting, as well as disease progression. Recent evidence suggests that CKD is characterized by abnormalities in GH and IGF-I signal transduction and the interaction of these pathways with those that involve other molecules such as ghrelin, myostatin, and the suppressor of cytokine signaling (SOCS) family. Further understanding of GH/IGF pathophysiology in CKD may lead to the development of therapeutic strategies for these devastating complications, which are associated with high rates of mortality and morbidity.

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Consequences of postnatally elevated insulin-like growth factor-II in transgenic mice: endocrine changes and effects on body and organ growth.

Abstract: Insulin-like growth factor-II

Cited by 83 publications

References 39 publications

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

Mechanisms of adrenal gland growth: signal integration by extracellular signal regulated kinases1/2

Regulation of steroidogenesis by insulin-like growth factors (IGFs) in adult human adrenocortical cells: IGF-I and, more potently, IGF-II preferentially enhance androgen biosynthesis through interaction with the IGF-I receptor and IGF-binding proteins

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

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