Sex steroid hormones and brain function:PETimaging as a tool for research

Abstract

Sex steroid hormones are major regulators of sexual characteristic among species. These hormones, however, are also produced in the brain. Steroidal hormone-mediated signalling via the corresponding hormone receptors can influence brain function at the cellular level and thus affect behaviour and higher brain functions. Altered steroid hormone signalling has been associated with psychiatric disorders, such as anxiety and depression.Neurosteroids are also considered to have a neuroprotective effect in neurodegenerative diseases. So far, the role of steroid hormone receptors in physiological and pathological conditions has mainly been investigated post mortem on animal or human brain tissues. To study the dynamic interplay between sex steroids, their receptors, brain function and behaviour in psychiatric and neurological disorders in a longitudinal manner, however, noninvasive techniques are needed. Positron emission tomography (PET) is a non-invasive imaging tool that is used to quantitatively investigate a variety of physiological and biochemical parameters in vivo. PET uses radiotracers aimed at a specific target (eg, receptor, enzyme, transporter) to visualise the processes of interest. In this review, we discuss the current status of the use of PET imaging for studying sex steroid hormones in the brain. So far, PET has mainly been investigated as a tool to measure (changes in) sex hormone receptor expression in the brain, to measure a key enzyme in the steroid synthesis pathway (aromatase) and to evaluate the effects of hormonal treatment by imaging specific downstream processes in the brain. Although validated radiotracers for a number of targets are still warranted, PET can already be a useful technique for steroid hormone research and facilitate the translation of interesting findings in animal studies to clinical trials in patients. K E Y W O R D Sandrogen receptor, neuroimaging, oestrogen receptor, positron emission tomography, sex steroid hormones | INTRODUCTIONSex steroid hormones are a family of steroidal hormones that can be divided into 3 classes: oestrogens, progestins and androgens. These hormones are major regulators of sexual functions, including the reproductive cycle, reproductive physiology and the development of accessory reproductive organs.1 However, our vision of the function of these hormones has been expanded because they not only regulate sexual behaviour, but also affect brain functions, such as memory, 2 anxiety-related behaviour 3 and other functions at the cellular level. 4 Sex steroid hormones are mainly synthesised by the ovaries and testis. The hypothalamic-pituitary-gonadal (HPG) axis is the main system by which the production and release of sex steroids is regulated. 5 Circulating sex hormones can stimulate the release ofThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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