Modulation of the growth hormone–insulin-like growth factor (GH–IGF) axis by pharmaceutical, nutraceutical and environmental xenobiotics: An emerging role for xenobiotic-metabolizing enzymes and the transcription factors regulating their expression. A review

Abstract

The growth hormone-insulin-like growth factor (GH-IGF) axis has gained considerable focus over recent years. One cause of this increased interest is due to a correlation of age-related decline in plasma GH/IGF levels with age-related degenerative processes, and it has led to the prescribing of GH replacement therapy by some practitioners. On the other hand, however, research has also focused on the pro-carcinogenic effects of high GH-IGF levels, providing strong impetus for finding regimes that reduce its activity. Whereas the effects of GH/IGF activity on the action of xenobiotic-metabolizing enzyme systems is reasonably well appreciated, the effects of xenobiotic exposure on the GH-IGF axis has not received substantial review. Relevant xenobiotics are derived from pharmaceutical, nutraceutical and environmental exposure, and many of the mechanisms involved are highly complex in nature, not easily predictable from existing in vitro tests and do not always predict well from in vivo animal models. After a review of the human and animal in vivo and in vitro literature, a framework for considering the different levels of direct and indirect modulation by xenobiotics is developed herein, and areas that still require further investigation are highlighted, i.e. the actions of common endocrine disruptors such as pesticides and phytoestrogens, as well as the role of xenobiotic-metabolizing enzymes and the transcription factors regulating their expression. It is anticipated that a fuller appreciation of the existing human paradigms for GH-IGF axis modulation gained through this review may help explain some of the variation in levels of plasma IGF-1 and its binding proteins in the population, aid in the prescription of particular dietary regimens to certain individuals such as those with particular medical conditions, guide the direction of long-term drug/nutraceutical safety trials, and stimulate ideas for future research. It also serves to warn athletes that using compounds touted as performance enhancing because they promote short-term GH release could in fact be detrimental to performance in the long-run.

Ameliorative Potential of Morin in Streptozotocin-Induced Neuropathic Pain in Rats

“…The growth-promoting properties of IGF-1 are reported in almost all biological tissues, especially liver, cartilage, bone, skeletal muscle, lungs, nerves, skin, and kidney. IGF-1 can also control the growth and development of nerve cells as well as synthesis of DNA [32]. In the present study, levels of both NGF and IGF-1 were markedly decreased in the sciatic nerves of the diabetic animals indicating loss of neurointegrity and increased rate of nerve cells apoptosis.…”

Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats

“…IGF is a neurological growth factor with a structure similar to that of insulin, and exhibits anabolic effects that inhibit neural cell apoptosis. Furthermore, IGF regulates DNA synthesis and thus the growth and proliferation of nerve cells (47). NGF performs a vital neuroprotective role with the ability to potentiate axonal growth.…”

Comparative transcriptome analysis of testes and ovaries for the discovery of novel genes from Amur sturgeon (Acipenser schrenckii)

“…GH promotes growthby increasing the concentration of glucose and free fatty acids (Ranabirand Reetu, 2011). In addition, GH also promotes growth by stimulating the production of insulin-like growth factor 1 (IGF-1) (Scarth, 2006). IGF-1 is generated in target tissues, making it both an endocrine and autocrine hormone (Jansen et al, 1983).…”