The Brain: Target and Source for Sex Steroid Hormones
There is a large body of evidence indicating that in the brain the action of sex hormones is not limited to the regulation of endocrine functions and mating behavior. In fact, the brain is one of the specific target tissues for sex steroid hormones and the identification of estrogen, progestin, and androgen receptors in numerous regions of the central nervous system (CNS) suggests a role for sex hormones in modulating different brain functions. The mechanism of action of these steroids in the CNS is similar to that observed in the peripheral target organs, producing both genomic and nongenomic effects. In the classical genomic mechanism of steroids, estrogen induces relatively long-term actions on neurons by activating specific intracellular receptors that modulate gene transcription and protein synthesis. Thus, gonadal steroids modulate the synthesis, release, and metabolism of many neuropeptides and neuroactive transmitters and the expression of their receptors (Table 1). Among the neurotransmitters, noradrenaline, dopamine, γ-aminobutirric acid (GABA), acetylcholine, serotonin, and melatonin are modulated by sex steroid hormones. The neuropeptides, which are directly influenced by gonadal hormones, include the opioid peptides, gonadotropin-releasing hormone (GnRH), corticotropin-releasing factor (CRF), neuropeptide Y (NPY), and galanin . Moreover, estrogen exerts very rapid effects in the brain that cannot be attributed to genomic mechanisms. These nongenomic effects of estrogen modulate electrical excitability, synaptic functioning, and morphological features, and are involved in many of the physiological functions and clinical effects of estrogen in the brain [2,3].
KeywordsEstrous Cycle Gonadal Steroid Premenstrual Syndrome Neuroactive Steroid Nongenomic Effect
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- 1.Speroff L, Glass RH, Kase NH. Clinical gynecological endocrinology and infertility. 5th edition. Baltimore, Maryland: Williams and Wilkins, 1995.Google Scholar
- 5.Bohus B, Koolhaas JM, Korte SM. Psychological stress, anxiety and depression: Physiological and neuroendocrine correlates in animal model In: Genazzani AR, Nappi G, Petraglia F, Martignoni E, editors. Stress and related disorders from adaptation to dysfunction. Carnforth, UK: The Parthenon Publishing Group, 1991:28–31.Google Scholar
- 9.Panay N, Sands RH, Studd JWW. Estrogen and behavior. In: Genazzani AR, Petraglia F, Purdy RH, editors. The brain: Source and target for sex steroid hormones. Carnforth, UK: The Parthenon Publishing Group, 1996:257–76.Google Scholar
- 11.Linghtman SL, Jacobs HS, Maguire AK, et al. Climateric flushing: Clinical and endocrine response to infusion of naloxone. Br J Obstet Gynec 1981;88:919–24.Google Scholar
- 13.Mc Loughin L, Grossman A, Tomlin S, et al. CRF-41 stimulates the release of beta-lipotropin and beta-endorphin in normal human subjects. Neuroendocrinology 1984;38: 282–84.Google Scholar
- 14.Karla SP. Gonadal steroid hormones promote interactive communication. In: Genazzani A R, Petraglia F, Purdy RH, editors. The brain: Source and target for sex steroid hormones. Carnforth, UK: The Parthenon Publishing Group, 1996:257–76.Google Scholar
- 18.Wooley C, McEwen BS. Estradiol regulates hippocampal dendritic spine density via an N-methyl-D-aspartate receptor-dependent mechanism. J Neurosci 1994;14:7680–87.Google Scholar
- 23.Barbaccia ML, Roscetti G, Trabucchi M, et al. Brain allopregnanolone concentrations and GABA A receptor function in stressed rats. Society for neuroscience, 1995. Abstract 408.Google Scholar
- 24.Patchev VK, Shoaib M, Holsboer F, Almeida OFX. The neurosteroid tetrahydroprogesterone counteracts corticotropin-releasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus. Neuroscience 1994;62:265.PubMedCrossRefGoogle Scholar
- 25.Genazzani AR, Salvestroni C, Guo A-L, et al. Neurosteroids and regulation of neuroendocrine function. In: Genazzani A R, Petraglia F, Purdy RH, editors. The brain: Source and target for sex steroid hormones. Carnforth, UK: The Parthenon Publishing Group, 1996: 83–91.Google Scholar
- 26.Wang M, Seippel L, Purdy RH, Backstrom T. Relationship between symptom severity and steroid variation in women with premenstrual syndrome: Study on serum pregnenolone sulfate, 5α-pregnan-3,20-dione and 3α-hydroxy-5α-pregnan-20-one. J Clin Endocrinol Metab 1996;81:1076–82.PubMedCrossRefGoogle Scholar