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Actions of Steroids: New Neurotransmitters - PubMed

  • ️Fri Jan 01 2016

Review

Actions of Steroids: New Neurotransmitters

Lauren M Rudolph et al. J Neurosci. 2016.

Abstract

Over the past two decades, the classical understanding of steroid action has been updated to include rapid, membrane-initiated, neurotransmitter-like functions. While steroids were known to function on very short time spans to induce physiological and behavioral changes, the mechanisms by which these changes occur are now becoming more clear. In avian systems, rapid estradiol effects can be mediated via local alterations in aromatase activity, which precisely regulates the temporal and spatial availability of estrogens. Acute regulation of brain-derived estrogens has been shown to rapidly affect sensorimotor function and sexual motivation in birds. In rodents, estrogens and progesterone are critical for reproduction, including preovulatory events and female sexual receptivity. Membrane progesterone receptor as well as classical progesterone receptor trafficked to the membrane mediate reproductive-related hypothalamic physiology, via second messenger systems with dopamine-induced cell signals. In addition to these relatively rapid actions, estrogen membrane-initiated signaling elicits changes in morphology. In the arcuate nucleus of the hypothalamus, these changes are needed for lordosis behavior. Recent evidence also demonstrates that membrane glucocorticoid receptor is present in numerous cell types and species, including mammals. Further, membrane glucocorticoid receptor influences glucocorticoid receptor translocation to the nucleus effecting transcriptional activity. The studies presented here underscore the evidence that steroids behave like neurotransmitters to regulate CNS functions. In the future, we hope to fully characterize steroid receptor-specific functions in the brain.

Copyright © 2016 the authors 0270-6474/16/3611449-10$15.00/0.

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Figures

Figure 1.
Figure 1.

Schematic representation of the dual action of estrogen hypothesis for the regulation of male sexual behavior. The nuclear-initiated effects of brain estrogens associated with long-term changes in gonadal testosterone secretion would activate the circuits underlying the expression of sexual behavior, while membrane-initiated effects would, in a manner similar to neuromodulators, acutely (within 15 min) modulate these primed circuits and determine whether animals engage in this behavior at a specific moment. These two complementary modes of action of the same chemical messenger would thus cooperate to regulate the long- and short-term aspect of the same behavior.

Figure 2.
Figure 2.

EMS induces dendritic spine formation in the ARH. A, During low estradiol conditions (e.g., diestrus), ARH neurons have a population of mature spines. B, Estradiol stimulates the ERα-mGluR1a signaling complex, leading to activation of PKC and LIM kinase (LIMK) and the phosphorylation of cofilin. This deactivation of cofilin allows for the formation of immature, filopodial spines. EMS stimulates gene expression through the activation of the MAPK pathway leading to CREB-mediated transcription. C, Spine maturation results in mushroom-shaped spines that are thought to be functional and stable. The time course of spine maturation coincides with the display of lordosis behavior in the female rat, beginning 20 h after estradiol treatment. Spine maturation is regulated by either gene transcription resulting from membrane to nucleus signaling (B) or direct nuclear action (C).

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