The prevailing classical hypotheses for the mechanism of steroid hormones action postulate their genomic action. The signal is transmitted by the binding of steroids to the specific membrane, cytoplasmic and/or nuclear receptors, and next, these complexes modify the transcription of hormone-sensitive genes. Now it is proposed that the rapid steroid actions at the plasma membrane level could precede their traditional genomic mechanisms. There are two main patterns of nongenomic action. The first is linked with direct steroid interaction with the membrane proteins not being the specific receptors. The second way is the modulation of intracellular signaling systems by the steroid-receptor complex, but without contribution of transcriptional machinery. Interestingly, the hormones effects are detectable within minutes, and are insensitive to RNA and protein synthesis inhibitors.

Steroids have also a strong potential to modulate processes in the CNS, entailing diverse behavioral and psychopharmacological effects in humans and other species. Steroids that are able to regulate the neuron excitability in the CNS are named “neuroactive steroids”. Apart from endocrine glands, steroid hormones can be synthesized de novo in the brain, and the term “neurosteroids” was introduced for those synthesized in the CNS. The nervous tissue appears to be under permanent genomic and nongenomic control of steroids, although their concentrations are age- and sex-dependent, and notably differ in particular areas of the brain.

The nongenomic hormone action appears to be the very important alternative pathways in cellular signaling. The fast negative and positive modulatory effects were observed for g-aminobutyric acid (GABA_A) receptor complex, N-methyl-D-aspartate (NMDA) receptors, G proteins-coupled receptors, and ion channels and pumps. Steroids are able to activate ubiquitous regulatory cascades such as MAPK family members, PI3 kinase, Akt/protein kinase B, tyrosine kinases, protein kinases A and C, or phospholipases C and A₂, thereby can modulate generation of various second messengers, including Ca²⁺, IP₃, DAG, cAMP, cGMP and NO.

Disturbance in nervous cell homeostasis can alter both, nongenomic and genomic mechanisms in the brain leading to relevant pathophysiological consequences. The relationship between fast steroid-induced signaling and membrane-located effectors may represent an important area for future investigation to elucidate their potential role in neurodegenerative diseases, as well as in an eventual therapy.

Supported in part by the grants No 2 P05A 03529 and 503-6086-2

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/10808 must be provided.

1. Glutathione in PC12 cells with altered calcium homeostasis
2. The activity of p38 MAPK, ERK1/2, JNK in PC12 cells with altered Ca²⁺ homeostasis
3. Fast effect of estradiol on calcium transport in PC12 cells
4. A study on selected glutathione transferases in PC12 cells with disturbed calcium homeostasis