Life Sciences, Vol. 37, pp. 893-906 Pergamon Press Printed in the U.S.A. MINIREVIEW ROLE OF FEMALE GONADAL HORMONES IN THE CNS: CLINICAL AND EXPERIMENTAL ASPECTS Adriana Maggi and Jorge Perez Milano Molecular Pharmacology Laboratory Institute of Pharmacology and Pharmacognosy, University of Milan P.za Durante ii - 20131 Milan, Italy Introduction Various lines of evidence have clearly demonstrated that female steroid hormones carl act in the Central Nervous System (CNS), principally in the thalamic and hypothalamic areas, to regulate endocrine functions and sex related behavior. In the past few years, clinical observations have been accumulated suggesting that estrogens and progesterone may be involved also in the modulation of functions not strictly related to endocrine control. In fact, these hormones seem to par tecipate in the control of motor areas (as demonstrated by their effects on clinical or experimental tardive dyskinesia, chorea, epilepsy) and limbic areas (since they are reported to influence psychiatric disorders like depression and schizophrenia). However, it is still controversial whether these effects are secondary to the hormone action in the well known brain target areas (thus resulting in altered levels of gonado- tropins, etc.) or are due to a direct action of the sex steroids in the motor and limbic areas. The finding that receptors for progesterone and estrogens are present in numerous extrahypothalamic brain regions has given a new impulse to studies aimed at understanding whether these hormones are implicated also in the regulation of brain functions not related to endocrine control or sexual behavior. The goal of this report is to review the clinical and experimental data supporting a widespread effect of estrogens and progesterone in the C.N.S. of mammals. Areas target for sex hormones in the CNS of mammals In most of the mammalian species studied the major number of binding sites specific for estrogens carl be found in the following regions of the CNS: i) preop<ic area (nuclei preopticus-medialis and interstitialis, striae terminalis) ; 2) hypothalamic area (nuclei infundibularis, ventro-medialis, premammilaris-ventralis) ; and 3) amygdaloid area (nuclei medialis, corticalis and basalis) (i). Outside these three major areas other regions display estrogen binding activity: H-estradiol visibly accumulates in the septal nuclei and hippocampus 0024-3205/85 $3.00 + .00 Copyright (c) 1985 Pergamon Press Ltd.