Cellular and Molecular Mechanisms of the Effects of Sex Hormones on the Nervous System

Abstract

The mechanisms of the action of sex steroid hormones on the nervous system are related to both classical, intracellularly mediated effects and non-classical membrane effects due to binding to membrane receptors. Some steroids are capable of inducing rapid neurotransmitter-like effects, similar to those of dopamine or glutamate that alter the activity of neuronal systems via different types of receptors. The neuroactive steroids are endogenous neuromodulators synthesized in the brain and rapidly affecting neuronal excitability. Sex steroids exert many pleiotropic effects in the nervous system: they modulate main neurotransmitter systems, promote the viability of neurons, play an important role in myelination, and influence cognitive processes. Estradiol protects neurons from excitotoxic damage and increases neuronal survival. Progesterone stimulates neurological and functional recovery. Androgens also exhibit a wide array of neuroprotective effects in motoneurons, including supporting cell survival, axonal regeneration, and dendritic maintenance. Despite the considerable increase of sex hormones and neurosteroids research in recent years and the ongoing discovery of biochemical mechanisms of action, their role in neurodegenerative processes remains not well determined.

Expression of Androgen and Estrogen Receptors in the Human Lacrimal Gland

“…Testosterone and dihydrotestosterone are ligands for AR, while estrogens (estrone-E1, 17β-estradiol-E2, and estriol-E3) act through ER (ERα, ERβ, and GPER). SSHs act predominantly as intranuclear ligand-activated transcription factors, leading to slow transcription-dependent genomic actions [ 44 , 45 , 46 , 47 ]. The integration of all steroid actions in the cell coordinates outcomes such as cell fate, proliferation, differentiation, and migration [ 48 , 49 , 50 , 51 , 52 , 53 ].…”

Sex Differences and Role of Gonadal Hormones on Glutamate Level, After Spinal Cord Injury in Rats: A Microdialysis Study

“…As a neuroprotective agent, testosterone acts through multiple mechanisms, including attenuation of synaptic stripping (Bahnasy, El-Heneedy, & El-Seidy, 2018; Jones, Durica, & Jacob, 1997) and Glial Fibrillary Acidic Protein (GFAP), mediation of the central glial response (Coers, Tanzer, & Jones, 2002; Delchev & Georgieva, 2018; Jones, Coers, Storer, Tanzer, & Kinderman, 1999), and enhancement of the antioxidant enzymes (Ahlbom, Prins, & Ceccatelli, 2001), heat shock protein expression (Mancuso et al, 2018; Tetzlaff, Tanzer, & Jones, 2007; Zhang et al, 2004), ribosomal response (Kinderman & Jones, 1993), and the neurotrophin brain-derived neurotrophic factor (Verhovshek, Cai, Osborne, & Sengelaub, 2010).…”

Hormones and Sex-Specific Medicine in Human Physiopathology

“…More precisely, the activation of the receptors starts when estrogens bind to cytoplasmic ERs, which are then translocated to the nucleus. The ligand-receptor complex binds to a hormone response element, a particular supervisory DNA segment in the promoter region of genes, leading to the modulation of transcription and the mRNA modification [17]. More recent literature suggests that, apart from the typical genomic interaction of estrogens with their receptors, the binding of non-nuclear ERs may trigger prompt signaling pathways involved in various cell functions and has been detected in different histotypes, including nervous system cells and lymphocytes [9,[17][18][19].…”