Steroid Transport, Local Synthesis, and Signaling within the Brain: Roles in Neurogenesis, Neuroprotection, and Sexual Behaviors

Introduction: Pornography is the term given for non-relational sex without any requirements for relational intimacy. It has appeared in all cultures and civilizations over centuries. Research into the area of addictive sexual behaviors on the Internet incorporates the various constructs surrounding compulsive sexual behavior. Pornography and society: Excess viewing of pornography has been said to be associated with psychiatric comorbidities such as anxiety and depression, and even sexual dysfunction. Individuals with pornography addiction have lower degrees of social integration, increase in conduct problems, higher levels of delinquent behavior, higher incidence of depressive symptoms, and decreased emotional bonding with caregivers. Pornography is an expression of fantasies and is said to have the potential to rewire pleasure centers of the brain and alter structures and function. Conclusion: Pornography can bring about significant changes in the brain similar to what can be seen in drug addictions. Owing to the boom of technology and easy access to such material, it is imperative to provide specifically designed pornography addiction education programs to educate students about the adverse effects of pornography.

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Androgen action in the brain and spinal cord for the regulation of male sexual behaviors

Current Opinion in Pharmacology ◽

10.1016/j.coph.2008.08.010 ◽

2008 ◽

Vol 8 (6) ◽

pp. 747-751 ◽

Cited By ~ 28

Author(s):

K MATSUDA ◽

H SAKAMOTO ◽

M KAWATA

Keyword(s):

Spinal Cord ◽

Sexual Behaviors ◽

Androgen Action ◽

Brain And Spinal Cord ◽

The Brain

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Neurosteroids and GABAergic signaling in health and disease

BioMolecular Concepts ◽

10.1515/bmc-2012-0033 ◽

2013 ◽

Vol 4 (1) ◽

pp. 29-42 ◽

Cited By ~ 28

Author(s):

Georgina MacKenzie ◽

Jamie Maguire

Keyword(s):

Sexual Behaviors ◽

Neuronal Excitability ◽

De Novo ◽

Aminobutyric Acid ◽

Acid Type ◽

Direct Binding ◽

Health And Disease ◽

Local Metabolism ◽

The Brain ◽

Large Charge

AbstractEndogenous neurosteroids such as allopregnanolone, allotetrahydrodeoxycorticosterone, and androstanediol are synthesized either de novo in the brain from cholesterol or are generated from the local metabolism of peripherally derived progesterone or corticosterone. Fluctuations in neurosteroid concentrations are important in the regulation of a number of physiological responses including anxiety and stress, reproductive, and sexual behaviors. These effects are mediated in part by the direct binding of neurosteroids to γ-aminobutyric acid type-A receptors (GABAARs), resulting in the potentiation of GABAAR-mediated currents. Extrasynaptic GABAARs containing the δ subunit, which contribute to the tonic conductance, are particularly sensitive to low nanomolar concentrations of neurosteroids and are likely their preferential target. Considering the large charge transfer generated by these persistently open channels, even subtle changes in neurosteroid concentrations can have a major impact on neuronal excitability. Consequently, aberrant levels of neurosteroids have been implicated in numerous disorders, including, but not limited to, anxiety, neurodegenerative diseases, alcohol abuse, epilepsy, and depression. Here we review the modulation of GABAAR by neurosteroids and the consequences for health and disease.

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Neurosteroids, with special reference to the effect of progesterone on myelination in peripheral nerves

Multiple Sclerosis Journal ◽

10.1177/135245859700300209 ◽

1997 ◽

Vol 3 (2) ◽

pp. 105-112 ◽

Cited By ~ 29

Author(s):

E-E. Baulieu ◽

M. Schumacher

Keyword(s):

Sciatic Nerve ◽

Glial Cells ◽

Peripheral Nerves ◽

Basic Protein ◽

Membrane Receptors ◽

Neonatal Rat ◽

Myelin Proteins ◽

Local Synthesis ◽

The Brain ◽

Neonatal Rat Brain

Some steroids are synthesized within the central and peripheral nervous system, mostly by glial cells. These are known as neurosteroids. In the brain, neurosteroids have been shown to act directly on membrane receptors for neurotransmitters. For example, progesterone inhibits the neuronal nicotinic acetylcholine receptor, whereas its 3α,5α-reduced metabolite 3α,5α-tetrahydroprogesterone (allopregnanolone) activates the A γ-aminobutyric acid receptor complex. Besides these effects, neurosteroids also regulate important glial functions, such as the synthesis of myelin proteins. Thus, in cultures of glial cells prepared from neonatal rat brain, progesterone increases the number of oligodendrocytes expressing the myelin basic protein (MBP) and the 2',3'-cyclic nucleotide-3'-phophodiesterase (CNPase). An important role for neurosteroids in myelin repair has been demonstrated in the rodent sciatic nerve, where progesterone and its direct precursor pregnenolone are synthesized by Schwann cells. After cryolesion of the male mouse sciatic nerve, blocking the local synthesis or action of progesterone impairs remyelination of the regenerating axons, whereas administration of progesterone to the lesion site promotes the formation of new myelin sheaths.

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The Local Neuropeptide System of Keratinocytes

Biomedicines ◽

10.3390/biomedicines9121854 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1854

Author(s):

Nicola Cirillo

Keyword(s):

Human Skin ◽

Oral Mucosa ◽

Local Source ◽

Corticotropin Releasing Hormone ◽

Oral Keratinocytes ◽

Local Synthesis ◽

Skin Cells ◽

Hypothalamic Pituitary Axis ◽

And Function ◽

The Brain

Neuropeptides have been known for over 50 years as chemical signals in the brain. However, it is now well established that the synthesis of this class of peptides is not restricted to neurons. For example, human skin not only expresses several functional receptors for neuropeptides but, also, can serve as a local source of neuroactive molecules such as corticotropin-releasing hormone, melanocortins, and β-endorphin. In contrast, an equivalent of the hypothalamic-pituitary axis in the oral mucosa has not been well characterized to date. In view of the differences in the morphology and function of oral mucosal and skin cells, in this review I surveyed the existing evidence for a local synthesis of hypothalamic-pituitary, opiate, neurohypophyseal, and neuroendocrine neuropeptides in both epidermal and oral keratinocytes.

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Glutamate in Male and Female Sexual Behavior: Receptors, Transporters, and Steroid Independence

Frontiers in Behavioral Neuroscience ◽

10.3389/fnbeh.2020.589882 ◽

2020 ◽

Vol 14 ◽

Author(s):

Vic Shao-Chih Chiang ◽

Jin Ho Park

Keyword(s):

Sexual Behavior ◽

Sexual Behaviors ◽

Receptor Expression ◽

Neuron Activity ◽

Sexual Diversity ◽

Novel Treatments ◽

Molecular Events ◽

Integral Role ◽

The Brain

The survival of animal species predicates on the success of sexual reproduction. Neurotransmitters play an integral role in the expression of these sexual behaviors in the brain. Here, we review the role of glutamate in sexual behavior in rodents and non-rodent species for both males and females. These encompass the release of glutamate and correlations with glutamate receptor expression during sexual behavior. We then present the effects of glutamate on sexual behavior, as well as the effects of antagonists and agonists on different glutamate transporters and receptors. Following that, we discuss the potential role of glutamate on steroid-independent sexual behavior. Finally, we demonstrate the interaction of glutamate with other neurotransmitters to impact sexual behavior. These sexual behavior studies are crucial in the development of novel treatments of sexual dysfunction and in furthering our understanding of the complexity of sexual diversity. In the past decade, we have witnessed the burgeoning of novel techniques to study and manipulate neuron activity, to decode molecular events at the single-cell level, and to analyze behavioral data. They pose exciting avenues to gain further insight into future sexual behavior research. Taken together, this work conveys the essential role of glutamate in sexual behavior.

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Genetic Identification of GnRH Receptor Neurons: A New Model for Studying Neural Circuits Underlying Reproductive Physiology in the Mouse Brain

Endocrinology ◽

10.1210/en.2010-1208 ◽

2011 ◽

Vol 152 (4) ◽

pp. 1515-1526 ◽

Cited By ~ 51

Author(s):

Shuping Wen ◽

Iris N. Götze ◽

Oliver Mai ◽

Christian Schauer ◽

Trese Leinders-Zufall ◽

...

Keyword(s):

Mouse Brain ◽

Sexual Behaviors ◽

Gnrh Receptor ◽

Reproductive Physiology ◽

Genetic Identification ◽

Brain Areas ◽

Brain Functions ◽

Model Sets ◽

Lh Rh ◽

The Brain

Abstract GnRH signaling regulates reproductive physiology in vertebrates via the hypothalamic-pituitary-gonadal axis. In addition, GnRH signaling has been postulated to act on the brain. However, elucidating its functional role in the central nervous system has been hampered because of the difficulty in identifying direct GnRH signaling targets in live brain tissue. Here we used a binary genetic strategy to visualize GnRH receptor (GnRHR) neurons in the mouse brain and started to characterize these cells. First, we expressed different fluorescent proteins in GnRHR neurons and mapped their precise distribution throughout the brain. Remarkably, neuronal GnRHR expression was only initiated after postnatal day 16, suggesting peri- and postpubertal functions of GnRH signaling in this organ. GnRHR neurons were found in different brain areas. Many GnRHR neurons were identified in areas influencing sexual behaviors. Furthermore, GnRHR neurons were detected in brain areas that process olfactory and pheromonal cues, revealing one efferent pathway by which the neuroendocrine hypothalamus may influence the sensitivity towards chemosensory cues. Using confocal Ca2+ imaging in brain slices, we show that GnRHR neurons respond reproducibly to extracellular application of GnRH or its analog [D-TRP6]-LH-RH, indicating that these neurons express functional GnRHR. Interestingly, the duration and shape of the Ca2+ responses were similar within and different between brain areas, suggesting that GnRH signaling may differentially influence brain functions to affect reproductive success. Our new mouse model sets the stage to analyze the next level of GnRH signaling in reproductive physiology and behavior.

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Cortisol and corticosterone in the songbird immune and nervous systems: local vs. systemic levels during development

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00002.2008 ◽

2008 ◽

Vol 295 (1) ◽

pp. R103-R110 ◽

Cited By ~ 44

Author(s):

Kim L. Schmidt ◽

Kiran K. Soma

Keyword(s):

Immune System ◽

De Novo ◽

Solid Phase ◽

Bursa Of Fabricius ◽

Zebra Finches ◽

Local Synthesis ◽

Nervous Systems ◽

Immune Tissues ◽

Cortisol Levels ◽

The Brain

Glucocorticoids (GCs) have profound effects on the immune and nervous systems during development. However, circulating GC levels are low neonatally and show little response to stressors. This paradox could be resolved if immune and neural tissues locally synthesize GCs. Here, we measured baseline corticosterone and cortisol levels in plasma, immune organs, and brain regions of developing zebra finches. Steroids were extracted using solid phase-extraction and quantified using specific immunoassays. As expected, corticosterone was the predominant GC in plasma and increased with age. In contrast, cortisol was the predominant GC in immune tissues (bursa of Fabricius, thymus, spleen) and decreased with age. Cortisol levels in immune tissues were higher than cortisol levels in plasma. In the brain, corticosterone and cortisol levels were similarly low, providing little evidence for local synthesis of GCs in the brain. This is the first study to measure 1) cortisol in the plasma of songbirds, 2) corticosterone or cortisol in the brain of songbirds, and 3) corticosterone or cortisol in the immune system of any species. Despite the prevailing dogma that corticosterone is the primary GC in birds, these results indicate that cortisol is the predominant GC in the immune system of developing zebra finches. These results raise the hypothesis that cortisol is synthesized de novo from cholesterol in the immune system as an “immunosteroid,” analogous to neurosteroids synthesized in the brain. Local production of GCs in immune tissues may allow GCs to regulate lymphocyte selection while avoiding the costs of high systemic GCs during development.

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Nuclear Receptor Coactivators (NCOAs) and Corepressors (NCORs) in the Brain

Endocrinology ◽

10.1210/endocr/bqaa083 ◽

2020 ◽

Vol 161 (8) ◽

Cited By ~ 1

Author(s):

Zheng Sun ◽

Yong Xu

Keyword(s):

Nuclear Receptor ◽

Sexual Behaviors ◽

Transcriptional Activation ◽

Hormone Receptors ◽

Target Genes ◽

Autism Spectrum ◽

Mammalian Brain ◽

Dependent Manner ◽

Nuclear Receptor Coactivators ◽

The Brain

Abstract Nuclear receptor coactivators (NCOAs) and corepressors (NCORs) bind to nuclear hormone receptors in a ligand-dependent manner and mediate the transcriptional activation or repression of the downstream target genes in response to hormones, metabolites, xenobiotics, and drugs. NCOAs and NCORs are widely expressed in the mammalian brain. Studies using genetic animal models started to reveal pivotal roles of NCOAs/NCORs in the brain in regulating hormonal signaling, sexual behaviors, consummatory behaviors, exploratory and locomotor behaviors, moods, learning, and memory. Genetic variants of NCOAs or NCORs have begun to emerge from human patients with obesity, hormonal disruption, intellectual disability, or autism spectrum disorders. Here we review recent studies that shed light on the function of NCOAs and NCORs in the central nervous system.

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Angiotensin generation in the brain: a re-evaluation

Clinical Science ◽

10.1042/cs20180236 ◽

2018 ◽

Vol 132 (8) ◽

pp. 839-850 ◽

Cited By ~ 15

Author(s):

Estrellita Uijl ◽

Liwei Ren ◽

A.H. Jan Danser

Keyword(s):

Blood Brain Barrier ◽

Renin Angiotensin System ◽

Brain Barrier ◽

Ang Ii ◽

Independent Manner ◽

Neurogenic Hypertension ◽

Local Synthesis ◽

Blood Brain Barrier Disruption ◽

Blood Brain ◽

The Brain

The existence of a so-called brain renin-angiotensin system (RAS) is controversial. Given the presence of the blood–brain barrier, angiotensin generation in the brain, if occurring, should depend on local synthesis of renin and angiotensinogen. Yet, although initially brain-selective expression of intracellular renin was reported, data in intracellular renin knockout animals argue against a role for this renin in angiotensin generation. Moreover, renin levels in brain tissue at most represented renin in trapped blood. Additionally, in neurogenic hypertension brain prorenin up-regulation has been claimed, which would generate angiotensin following its binding to the (pro)renin receptor. However, recent studies reported no evidence for prorenin expression in the brain, nor for its selective up-regulation in neurogenic hypertension, and the (pro)renin receptor rather displays RAS-unrelated functions. Finally, although angiotensinogen mRNA is detectable in the brain, brain angiotensinogen protein levels are low, and even these low levels might be an overestimation due to assay artefacts. Taken together, independent angiotensin generation in the brain is unlikely. Indeed, brain angiotensin levels are extremely low, with angiotensin (Ang) I levels corresponding to the small amounts of Ang I in trapped blood plasma, and Ang II levels at most representing Ang II bound to (vascular) brain Ang II type 1 receptors. This review concludes with a unifying concept proposing the blood origin of angiotensin in the brain, possibly resulting in increased levels following blood–brain barrier disruption (e.g. due to hypertension), and suggesting that interfering with either intracellular renin or the (pro)renin receptor has consequences in an RAS-independent manner.

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