Introduction

Steroid hormones can be divided into five classes: progestins, estrogens, androgens, glucocorticosteroids, and mineralocorticosteroids. The principal site of synthesis are the corpus luteum and the placenta for the progestatifs, the ovary or testes for the estrogens or androgens, and the adrenal glands for the glucocorticosteroids and mineralocorticosteroids. Until rather recently, it was thought that steroid hormones were synthesized exclusively in peripheral tissues, as previously mentioned. Some evidence has, however, demonstrated that steroids are also synthesized in the nervous system (1-3). An important part of the interest in these neurosteroids comes from the fact that their synthesis is independent of the endocrine glands, suggesting that they may represent key modulators of neuronal activities.

Although direct correlations between steroid concentrations and psychological status are not readily established, it is generally accepted that modifications can occur in response to hormonal levels. The mood alterations that take place in women during the ovarian cycle or at menopause can lead to the simple hypothesis that some brain functions may be modulated by sex hormones. Moreover, clinical profiles such as premenstrual syndrome or postpartum depression reinforce the notion that abrupt changes in the levels of sex hormones can be linked with psychological disorders (4). The first experimental evidence of the action of steroid hormones on brain activity was provided in the late 1950s

From: Contemporary Endocrinology: Neurosteroids: A New Regulatory Function in the Nervous System Edited by: E.-E. Baulieu, P. Robel, and M. Schumacher © Humana Press Inc., Totowa, NJ

by the work of Kawakami and Sawyer (5), who observed that thresholds for electroencephalogram (EEG) arousal and for the induction of "paradoxical sleep" in rabbits were influenced by estrogens. Electrophysiological experiments providing an initial demonstration of the action of steroids on neuronal activities were carried out by Lincoln and Cross (6,7). Using electrodes implanted into rat brains, they observed a modification of neuronal activity in the hypothalamus, septum and preoptic area following estrogen administration(6,7). Such observations were later confirmed by other investigators (8,9). More recently, extracellular and/or intracellular recordings from hippocampus slices have demonstrated a direct effect of estrogens, androgens, and corticosteroids on synaptic transmission (10-12). In parallel, numerous histological studies reported that steroids are able to promote and/or modulate dendritic length (13), as well as dendritic spine density (14-16). A decisive step for elucidating the molecular effect of steroids in the brain was achieved by Majewska (17), Harrison (18), and colleagues who showed that steroids modulate the GABAa receptor (GABAaR) located in the outer membranes of some nerve cells and induce a potentiation of the GABA-evoked currents. Following these crucial observations, numerous studies have dissected the multiple interactions of steroids with the ionotropic GABAAR, which belong to the superfamily of ligand-gated channels (19-21).

From PMS To PPD

From PMS To PPD

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