Actin Cytoskeleton Remodelling by Sex Steroids in Neurones

Abstract

Sex steroid hormones are fundamental regulators of cell growth, proliferation and migration. Oestrogens direct the development of tissues and organs (1) and orchestrate cell growth and proliferation during adult life (2). Cells respond to the environment through the expression of transmembrane receptors that sense extracellular stimuli and activate an elaborate network of intracellular signalling molecules. Given the large number of different signalling molecules and the complex relationships between them, a major challenge is to understand how specific signals generate unique responses. The architecture of signalling networks plays an important role in achieving signalling specificity (3).Cell morphology and its interaction with the extracellular environment requires a number of regulators orchestrating the different cytoskeletal components and their interactions with the cell membrane and anchorage proteins (4). Recent findings indicate that the extranuclear signalling of oestrogen is a fundamental regulator of cell morphology in diverse cellular lines, including neurones (5,6), and that many of these actions are played via rapid signalling to the actin cytoskeleton achieved via actin recruitment (7-11).The present review describes and discusses the current understanding of the regulatory actions of sex steroids on the cytoskeleton of neurones, with the aim of highlighting how these hormones influence the turnover of dendritic spines. Sex steroids and the brainThe brain is an important target of sex steroids that play multiple regulatory roles. These hormones are powerful mediators of dynamic brain differentiation into a male or female phenotype. This phenomenon has been originally described in studies on neuronal cell migration in the developing pre-optic area ⁄ anterior hypothalamus (12-15). The effects of sex hormones turn into differences in neuronal cell number, glial complexity, neurochemical expression Journal of NeuroendocrinologyCorrespondence to: T. Simoncini, Molecular and Cellular Gynecological Endocrinology Laboratory (MCGEL), Department of Reproductive Medicine and Child Development, Division of Obstetrics and Gynecology, University of Pisa, Via Roma, 57, 56100 Pisa, Italy (e-mail: tommaso.simoncini@ med.unipi.it).Cell morphology and its interaction with the extracellular environment are integrated processes involving a number of intracellular controllers orchestrating cytoskeletal proteins and their interaction with the cell membrane and anchorage proteins. Sex steroids are effective regulators of cell morphology and tissue organisation, and recent evidence indicates that this is obtained through the regulation of the actin cytoskeleton. Intriguingly, many of these regulatory actions related to cell morphology are achieved through the rapid, nonclassical signalling of sex steroid receptors to kinase cascades, independently from nuclear alteration of gene expression or protein synthesis. The identification of the mechanistic basis for these rapid actions on cell cytoskeleton has special relevance...

Plasticity in the olfactory bulb of the maternal mouse is prevented by gestational stress

“…For example the mechanisms involved in motherhood-induced enhanced dendritic complexity of bulbar neurons and on the prevention of this effect in stressed mothers remain to be determined. Unfortunately, the role of the different factors known to impact dendritic development, such as cytoskeletal and transcriptional factors5152, as well as sex and stress hormones535455, has yet to be studied in the context of olfactory neurogenesis and dendritogenesis. Nevertheless, in the context of motherhood, it is likely that sex steroids, whose levels change at the time of parturition and during lactation, may be involved.…”

“…Nevertheless, in the context of motherhood, it is likely that sex steroids, whose levels change at the time of parturition and during lactation, may be involved. Indeed, progesterone and estradiol, along with prolactin and oxytocin show variations that were found to modify maternal responsiveness3456 and most of them were found to modulate dendritic growth53545557, albeit in systems other than the olfactory bulb. Another very likely candidate is GABA, one of the few factors known to modulate dendritogenesis in the OB.…”

Integrating Neural Circuits Controlling Female Sexual Behavior

“…In the ARH, an increase in β-actin immunoreactivity is correlated an increase in spines demonstrated with Golgi staining (Christensen et al, 2011). Estrogenic regulation of spinogenesis was shown to involve ERα-mGluR1a signaling leading to modulation of actin dynamics through phosphorylation of molecules important for spine formation including cofilin, an actin depolymerizing factor (for review see Sarmiere and Bamburg, 2004; Hotulainen and Hoogenraad, 2010; Sanchez et al, 2012). Cofilin must be deactivated (phosphorylated) to allow the formation of filamentous actin and new spines (Bamburg, 1999; Meng et al, 2002).…”

Expression of cytoskeletal and molt-related genes is temporally scheduled in the hypodermis of the crayfish Procambarus clarkii during premolt

“…A variety of effectors of the expression of cytoskeletal genes are also well documented (e.g. Girard et al, 1996;Jones et al, 1999;Mayfield et al, 2010;Müller et al, 2007;Sanchez et al, 2012;Sántha et al, 2013). The changes in the expression of actin system members may be related here to increasing ecdysteroid levels, but owing to the complexity of the expression patterns, other factors are hypothesized to be involved as well.…”