Oestrogen, ocular function and low-level vision: a review
- College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester LE1 9HN, UK
1Harvard Medical School, Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
2Division of Biomedical Sciences, St George's Medical School, University of London, London SW17 0RE, UK
- Correspondence should be addressed to C V Hutchinson; Email: ch190{at}le.ac.uk
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Figure 1
Synthesis of oestrogens. Structures of the three main types of oestrogen are shown: E1, oestradiol (E2) and E3. Oestrogens are synthesised from androgens, testosterone and androstenedione, by the enzyme aromatase. The aromatase inhibitor anastrozole is used in the treatment of breast cancer after surgery to inhibit the synthesis of oestrogens. Oestrogens are produced primarily in the ovaries, but also in smaller amounts in liver, adrenal glands, breast and neurons.
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Figure 2
Oestrogen-regulated signalling pathways that could affect retinal function and health. The nuclear-initiated signalling response of oestrogens is mediated by the classical oestrogen receptors (ERs – ERα and ERβ), which relocate to the nucleus after ligand binding and dimerisation. By binding to estrogen-response elements (ERE) at specific target genes, ERs can activate transcription. E1 and oestradiol can also bind to ERs (ERα, ERβ and G-protein-coupled oestrogen receptor (GPER)) located at the cell membrane and rapidly activate signalling pathways including the RAS/ERK, PI3K/AKT and cAMP/PKA pathways. These can influence transcription, cytoskeleton remodelling, apoptosis/cell survival as well as neuron-specific functions, such as transmitter release and synaptic plasticity. Dysregulation of these processes could be important in visual dysfunction. There is considerable cross-talk between ERs and other receptors such as insulin-like growth factor receptor (IGF1R) and epidermal growth factor receptor (EGFR). Note: oestrogen has a higher affinity for ERα than ERβ. AC, adenylyl cyclase; PKA, protein kinase A, MMP, metalloproteinase, PI3K, phosphoinositide 3-kinase, GSK3β, glycogen synthase kinase 3β. G15 is a GPER antagonist. A full colour version of this figure available via http://dx.doi.org/10.1530/JOE-14-0349.
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Figure 3
Putative cardiovascular effects of oestrogen. Oestradiol activates two brain areas to decrease heart rate via the parasympathetic nervous system. The rostral ventrolateral medulla (RVLM) is activated via ERβ receptors and the nucleus ambiguous (NA) is activated via GPER. This decreased heart rate might decrease hypertension-related visual pathologies. One oestradiol metabolite is 2-methoxyestradiol, which can decrease smooth muscle cell proliferation in blood vessels, also reducing hypertension. A full colour version of this figure available via http://dx.doi.org/10.1530/JOE-14-0349.
- © 2014 Society for Endocrinology
