On the role of sex steroids in biological functions by classical and non-classical pathways. An update

Abstract

The sex steroid hormones (SSHs) play several roles in regulation of various processes in the cardiovascular, immune, muscular and neural systems. SSHs affect prenatal and postnatal development of various brain structures, including regions associated with important physiological, behavioral, cognitive, and emotional functions. This action can be mediated by either intracellular or transmembrane receptors. While the classical mechanisms of SSHs action are relatively well examined, the physiological importance of non-classical mechanism of SSHs action through membrane-associated and transmembrane receptors in the brain remains unclear. The most recent summary describing the role of SSHs in different body systems is lacking. Therefore, the aim of this review is to discuss classical and non-classical signaling pathways of testosterone and estradiol action via their receptors at functional, cellular, tissue level and to describe the effects on various body systems and behavior. Particular emphasis will be on brain regions including the hippocampus, hypothalamus, frontal cortex and cerebellum.

Steroid Sulfation in Neurodegenerative Diseases

“…Regarding the unconjugated steroids, the reactions between DHEA and androst-5-ene-3β,17β-diol, androstenedione and testosterone and estrone and estradiol are preferentially conducted in the reductase direction (Purohit and Foster, 2012;Mostaghel, 2013). generally act as neuroprotective substances (Fargo et al, 2009;Spence and Voskuhl, 2012;Duong et al, 2020;Yang et al, 2020) and promote neurogenesis and neuro-regeneration (Pillerová et al, 2021;Azcoitia et al, 2019). These processes in the brain take place through classical nuclear steroid receptors (estrogen receptor α and β-ERα and ERβ, androgen receptor-AR, progesterone receptor-PR), non-classical membraneassociated steroid receptors (AR, ERα, ERβ) and transmembrane receptors (zinc transporter protein 9, G protein coupled estrogen receptor 1) (Pillerová et al, 2021).…”

“…Particularly E2 exert pleiotropic effects there, facilitating learning and memory ( Frick, 2015 ; Sun et al, 2019 ; Luine and Frankfurt, 2012 ; Tozzi et al, 2020 ; Dieni et al, 2020 ), as well as influencing emotional ( Altemus, 2019 ) and sexual behavior ( Diotel et al, 2018 ). They generally act as neuroprotective substances ( Fargo et al, 2009 ; Spence and Voskuhl, 2012 ; Duong et al, 2020 ; Yang et al, 2020 ) and promote neurogenesis and neuro-regeneration ( Pillerová et al, 2021 ; Azcoitia et al, 2019 ). These processes in the brain take place through classical nuclear steroid receptors (estrogen receptor α and β-ERα and ERβ, androgen receptor-AR, progesterone receptor-PR), non-classical membrane-associated steroid receptors (AR, ERα, ERβ) and transmembrane receptors (zinc transporter protein 9, G protein coupled estrogen receptor 1) ( Pillerová et al, 2021 ).…”

“…They generally act as neuroprotective substances ( Fargo et al, 2009 ; Spence and Voskuhl, 2012 ; Duong et al, 2020 ; Yang et al, 2020 ) and promote neurogenesis and neuro-regeneration ( Pillerová et al, 2021 ; Azcoitia et al, 2019 ). These processes in the brain take place through classical nuclear steroid receptors (estrogen receptor α and β-ERα and ERβ, androgen receptor-AR, progesterone receptor-PR), non-classical membrane-associated steroid receptors (AR, ERα, ERβ) and transmembrane receptors (zinc transporter protein 9, G protein coupled estrogen receptor 1) ( Pillerová et al, 2021 ). Finally, E2 can exert its action through neurotransmitter receptors such as serotonin receptor ( Wetzel et al, 1998 ), L-type voltage gated channel ( Sribnick et al, 2009 ; Vega-Vela et al, 2017 ; Sánchez et al, 2014 ) or N-methyl-D-aspartate (NMDA) receptor ( Weaver et al, 1997 ; Foy et al, 1999 ).…”

Molecular actions of sex hormones in the brain and their potential treatment use in anxiety disorders

“…Slow, classical processes, which last usually several hours, are mediating the transcription of specific genes in the nucleus. On the other hand, fast, non-classical signaling stimulates various extranuclear downstream cascades regulating different cellular responses, such as DNA synthesis, cell proliferation, migration, or survival ( 20 ). The dysregulation of physiological concentrations of SSHs during prenatal and early postnatal development may influence the formation of brain structures and lead to various affective, neurodevelopmental, or neurodegenerative disorders ( 12 , 13 , 21 , 22 ).…”

The Mechanisms and Management of Age-Related Oxidative Stress in Male Hypogonadism Associated with Non-communicable Chronic Disease

“…Steroid sex hormones are classified as androgens, estrogens, and progestogens. Although all three classes are important in male and female physiology, androgens are associated with "musculisation" effects and are considered primarily male sex hormones [ 1 ]. Androgens have diverse functions in muscle physiology, lean body mass, the regulation of adipose tissue, bone density, neurocognitive regulation, and spermatogenesis, male reproductive and sexual function [ 2 ].…”