Review Endocrine induced changes in brain function during pregnancy ☆ Paula J. Brunton, John A. Russell ⁎ Laboratory of Neuroendocrinology, Centre for Integrative Physiology, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK ARTICLE INFO ABSTRACT Article history: Accepted 16 September 2010 Available online 22 September 2010 The female sex steroid hormones, estrogens and progesterone, are produced in large amounts in pregnancy, increasing as pregnancy progresses. These hormones have essential peripheral actions to maintain pregnancy, and to secure safe delivery at term. They also have important actions on the brain in pregnancy, generally through interactions with neuropeptide systems in the brain, or through modulating the actions of circulating peptide hormones on the brain. Together, these steroid–peptide links form short chains that evoke changes in central physiological systems that favour the pregnancy, including altered control of water and electrolyte balance, appetite and energy partitioning and stress responses. In parallel such links prepare the brain, through inhibition of oxytocin secretion until it is needed to support parturition and for immediate expression of maternal behaviour postpartum. We focus here on recent advances in understanding some of these steroid– peptide links, especially on non-classical progesterone actions through allopregnanolone, its neuroactive steroid metabolite, and opioid peptide mechanisms. © 2010 Elsevier B.V. All rights reserved. Keywords: Allopregnanolone Estradiol HPA axis Oxytocin Progesterone Relaxin Contents 1. Introduction .......................................................... 199 1.1. Sex steroid hormones in pregnancy ......................................... 201 1.2. Peripheral peptide hormones and the brain in pregnancy .............................. 202 BRAIN RESEARCH 1364 (2010) 198 – 215 ☆ Special Issue: “New Insights into the Neurobiology of Reproduction and Puberty” for Brain Research. Editors: Tony M. Plant and David R. Mann. ⁎ Corresponding author. Fax: +44 131 650 2872. E-mail address: J.A.Russell@ed.ac.uk (J.A. Russell). Abbreviations: 3α-HSD, 3α-hydroxysteroid dehydrogenase; 5αR, 5α-reductase; ACTH, adrenocorticotropic hormone; AgRP, agouti related peptide; α-MSH, α-melanocyte stimulating hormone; AII, angiotensin II; ANP, atrial natriuretic peptide; AVPV, anteroventral periventricular nucleus; CCK, cholecystokinin; CART, cocaine and amphetamine regulated transcript; CRH, corticotropin releasing hormone; DHP, dihydroprogesterone; DNA, deoxyribonucleic acid; ERα, estrogen receptor alpha; ERRα, estrogen related receptor alpha; ERβ, estrogen receptor-beta; GABA, gamma-aminobutyric acid; GnRH, gonadotropin releasing hormone; GPR30, G protein-coupled receptor 30; GPR54, G protein-coupled receptor 54; KiSS, kisspeptin; KISS1R, Kisspeptin1-derived peptide receptor; HPA, hypothalamo- pituitary-adrenal; MAP, mitogen activated protein; MnPO, median preoptic nucleus; mPOA, medial preoptic area; mRNA, messenger ribonucleic acid; NMDA, N-methyl-D-aspartic acid; NPY, neuropeptide Y; NTS, nucleus tractus solitarii; Ob-Rb, leptin receptor (long form); OVLT, organum vasculosum of the lamina terminalis; pPVN, parvocellular paraventricular nucleus; PL, placental lactogen; pENK-A, proenkephalin-A; pSTAT3, phosphorylated signal transducer and activator of transcription 3; POMC, pro-opiomelanocortin; PR, progesterone receptor; SFO, subfornical organ; SON, supraoptic nucleus; VMH, ventromedial hypothalamus 0006-8993/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2010.09.062 available at www.sciencedirect.com www.elsevier.com/locate/brainres