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Neuroactive steroids in the neuroendocrine control of food intake, metabolism, and reproduction

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Abstract

Neuroactive steroids are a type of steroid hormones produced within the nervous system or in peripheral glands and then transported to the brain to exert their neuromodulatory effects. Neuroactive steroids have pleiotropic effects, that include promoting myelination, neuroplasticity, and brain development. They also regulate important physiological functions, such as metabolism, feeding, reproduction, and stress response. The homoeostatic processes of metabolism and reproduction are closely linked and mutually dependent. Reproductive events, such as pregnancy, bring about significant changes in metabolism, and metabolic status may affect reproductive function in mammals. In females, the regulation of reproduction and energy balance is controlled by the fluctuations of oestradiol and progesterone throughout the menstrual cycle. Neurosteroids play a key role in the neuroendocrine control of reproduction. The synthesis of neuroestradiol and neuroprogesterone within the brain is a crucial process that facilitates the release of GnRH and LH, which in turn, regulate the transition from oestrogen-negative to oestrogen-positive feedback. In addition to their function in the reproductive system, oestrogen has a key role in the regulation of energy homoeostasis by acting at central and peripheral levels. The oestrogenic effects on body weight homoeostasis are primarily mediated by oestrogen receptors-α (ERα), which are abundantly expressed in multiple brain regions that are implicated in the regulation of food intake, basal metabolism, thermogenesis, and brown tissue distribution. The tight interplay between energy balance and reproductive physiology is facilitated by shared regulatory pathways, namely POMC, NPY and kisspeptin neurons, which are targets of oestrogen regulation and likely participate in different aspects of the joint control of energy balance and reproductive function. The aim of this review is to present a summary of the progress made in uncovering shared regulatory pathways that facilitate the tight coupling between energy balance and reproductive physiology, as well as their reciprocal interactions and the modulation induced by neurosteroids.

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Authors and Affiliations

  1. Institute of Medical Physiology “Richard Burian”, School of Medicine, University of Belgrade, Belgrade, Serbia

    Aleksandra Rasic-Markovic, Emilija Djuric, Daniel Skrijelj, Nikola Sutulovic, Dragan Hrncic & Olivera Stanojlovic

  2. Department of Endocrinology, UMC Bežanijska kosa, School of Medicine, University of Belgrade, Belgrade, Serbia

    Jelica Bjekic-Macut

  3. Department of Biochemistry, Institute for Biological Research “Siniša Stanković” - National Institute of Republic of Serbia, University of Belgrade, Belgrade, Serbia

    Đurđica Ignjatovic

  4. Institute of Pathophysiology, School of Medicine, University of Belgrade, Belgrade, Serbia

    Dusan Mladenovic

  5. Department of Endocrinology, Internal Medicine Clinic, University Clinical Centre of the Republic of Srpska, Faculty of Medicine, University of Banja Luka, Banja Luka, Bosnia and Herzegovina

    Aleksandra Marković

  6. Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center Niš, Faculty of Medicine, University of Niš, Niš, Serbia

    Saša Radenković

  7. Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia, Belgrade, Serbia

    Lena Radić

  8. Serbian Academy of Sciences and Arts, Belgrade, Serbia

    Nebojsa Radunovic

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  1. Aleksandra Rasic-Markovic
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Rasic-Markovic, A., Djuric, E., Skrijelj, D. et al. Neuroactive steroids in the neuroendocrine control of food intake, metabolism, and reproduction. Endocrine (2024). https://doi.org/10.1007/s12020-024-03755-x

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