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      Progesterone Signaling Mechanisms in Brain and Behavior

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          Steroid hormone, progesterone, modulates neuroendocrine functions in the central nervous system resulting in alterations in physiology and behavior. These neuronal effects are mediated primarily by intracellular progestin receptors (PRs) in the steroid-sensitive neurons, resulting in transcription-dependent genomic actions (classical mechanism). In addition to progesterone, intracellular PRs can also be activated in a “ligand-independent” manner by neurotransmitters, peptide growth factors, cyclic nucleotides, and neurosteroids. Recent studies indicate that rapid, non-classical progesterone actions involving cytoplasmic kinase signaling and/or extranuclear PRs can result in both transcription-independent and transcription-dependent actions. Cross-talk between extranuclear and classical intracellular signaling pathways promotes progesterone-dependent behavior in mammals. This review focuses on the mechanisms by which progesterone-initiated signaling mechanisms converge with PRs in the brain to modulate reproductive behavior in female rodents.

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          Most cited references 148

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          Src family protein tyrosine kinases are activated following engagement of many different classes of cellular receptors and participate in signaling pathways that control a diverse spectrum of receptor-induced biological activities. While several of these kinases have evolved to play distinct roles in specific receptor pathways, there is considerable redundancy in the functions of these kinases, both with respect to the receptor pathways that activate these kinases and the downstream effectors that mediate their biological activities. This chapter reviews the evidence implicating Src family kinases in specific receptor pathways and describes the mechanisms leading to their activation, the targets that interact with these kinases, and the biological events that they regulate.
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              The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes.

              Xenopus oocytes convert a continuously variable stimulus, the concentration of the maturation-inducing hormone progesterone, into an all-or-none biological response-oocyte maturation. Here evidence is presented that the all-or-none character of the response is generated by the mitogen-activated protein kinase (MAPK) cascade. Analysis of individual oocytes showed that the response of MAPK to progesterone or Mos was equivalent to that of a cooperative enzyme with a Hill coefficient of at least 35, more than 10 times the Hill coefficient for the binding of oxygen to hemoglobin. The response can be accounted for by the intrinsic ultrasensitivity of the oocyte's MAPK cascade and a positive feedback loop in which the cascade is embedded. These findings provide a biochemical rationale for the all-or-none character of this cell fate switch.

                Author and article information

                Front Endocrinol (Lausanne)
                Front Endocrinol (Lausanne)
                Front. Endocrin.
                Frontiers in Endocrinology
                Frontiers Research Foundation
                26 December 2011
                30 January 2012
                : 3
                1simpleCenter on Addiction, Learning and Memory, Department of Neuroscience, Baylor College of Medicine Houston, TX, USA
                2simpleDepartment of Molecular and Cellular Biology, Baylor College of Medicine Houston, TX, USA
                Author notes

                Edited by: Kazuyoshi Tsutsui, Waseda University, Japan

                Reviewed by: Suguru Kawato, University of Tokyo, Japan; Nobuhiro Harada, Fujita Health University School of Medicine, Japan

                *Correspondence: Shaila K. Mani, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. e-mail: smani@

                This article was submitted to Frontiers in Neuroendocrine Science, a specialty of Frontiers in Endocrinology.

                Copyright © 2012 Mani and Oyola.

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 140, Pages: 8, Words: 8494
                Review Article

                Endocrinology & Diabetes

                cross-talk, progesterone, dopamine, non-classical, progestin receptors, signaling


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