The hypothalamic-pituitary (HP) axis is the central regulator of endocrine action, controlling the function of a number of endocrine glands including thyroid, adrenal, gonadal and the growth hormone (GH)/insulin growth factor-1 (IGF-1) system, which modulate a myriad of physiological processes. The HP axis integrates various stimuli, including those generated internally such as energy levels, stress, inflammation and also in response to external stimuli (dark/light cycles and temperature) (Petrescu et al., 2018) and orchestrates endocrine outputs which control numerous physiological processes. The role of endocrine hormones and growth factors are interlinked, often being involved in the same cellular functions leading to crosstalk between the pathways and demonstrating bi-functional roles. Moreover, alterations in signalling through these pathways leads to a diverse number of diseases including many cancers, neurodevelopmental disorders and metabolic syndromes, highlighting the critical importance of understanding the precise regulation of these pathways and their interconnectivity. Furthermore, sex steroids crosstalk with several growth factors such as the epidermal growth factor (EGF) (Auricchio et al., 2008), fibroblast growth factor (FGF) (Smith et al., 2002), vascular endothelial growth factor (VEGF) (Hyder, 2006), transforming growth factor (TGF), platelet-derived growth factor (PDGF) (Schmahl et al., 2008), nerve growth factor (NGF) (Luo et al., 2018), and IGF in both normal and cancerous cells (Kenney and Dickson, 1996). This occurs at a number of different levels to influence cellular processes, including the production of steroids (Schmahl et al., 2008; Luo et al., 2018). Many of these growth factors are also known to be involved in mechanisms of resistance to endocrine therapies for the treatment of breast and prostate cancer (Schiff et al., 2003). This review aims to outline the role of the IGF/IGF-1R and steroid hormone interplay during normal growth and development, followed by an in-depth look at how these pathways impact metabolism and the potential consequences of this in the development of endocrine-related cancers.

6 May, 2022

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