There are some main neurosteroids developed in the brain which helps for some main human behaviour like sexual behaviour and memory, this neurosteroids are called allopregnanolone and pregnenolone sulfate. There are many sites where active novo steroid synthesis is taking place because of the Steroidogenic acute regulatory protein(StAR). The experiments on human and mouse are also therefore evidence for the presence of mRNA and protein in glia and nerous and also neurosteroidgenesis and StAR are results for cholesterol cleavage enzyme. Thus StAr is playing a main role in producing neurosteroids and the change in StAR mainly effects steroidogenesis in gonadal and adrenal.
7. Steroid functionality in neurosystem
Recent data implicate locally produced steroids, termed neurosteroids, as regulators of neuronal function. Adrenal and gonadal steroidogenesis is controlled by changes in the steroidogenic acute regulatory protein (StAR); however, little is known about the regulation of neurosteroid production. The StAR mRNA and protein are expressed within glia and neurons in discrete regions of the mouse brain, and that glial StAR expression is inducible. Consistent with a role in de novo neurosteroidogenesis, StAR colocalizes with the cholesterol side-chain cleavage enzyme P450scc in both mouse and human brains. These data support a role for StAR in the production of neurosteroids and identify potential sites of active de novo steroid synthesis in the brain.
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There are some main neurosteroids developed in the brain which helps for some main human behaviour like sexual behaviour and memory, this neurosteroids are called allopregnanolone and pregnenolone sulfate.
The local production of neurosteroids such as allopregnanolone and pregnenolone sulfate in the brain has been implicated in the regulation of many important functions, such as sexual behavior and memory.
Neurosteroids are synthesized in the central and peripheral nervous system, particularly but not exclusively in myelinating glial cells, from cholesterol or steroidal precursors imported from peripheral sources. They include 3 beta-hydroxy-delta 5-compounds, such as pregnenolone (PREG) and dehydroepiandrosterone (DHEA), their sulfates, and reduced metabolites such as the tetrahydroderivative of progesterone 3 alpha-hydroxy-5 alpha-pregnane-20-one (3 alpha,5 alpha-THPROG). These compounds can act as allosteric modulators of neurotransmitter receptors, such as GABAA, NMDA, and sigma receptors. Progesterone (PROG) is also a neurosteroid, and a progesterone receptor (PROG-R) has been identified in peripheral and central glial cells. At different places in the brain, neurosteroid concentrations vary according to environmental and behavioral circumstances, such as stress, sex recognition, or aggressiveness. A physiological function of neurosteroids in the central nervous system is strongly suggested by the role of hippocampal PREGS with respect to memory, observed in aging rats. In the peripheral nervous system, a role for PROG synthesized in Schwann cells has been demonstrated in the repair of myelin after cryolesion of the sciatic nerve in vivo and in cultures of dorsal root ganglia neurites. It may be important to study the effect of abnormal neurosteroid concentrations/metabolism with a view to the possible treatment of functional and trophic disturbances of the nervous system. Steroids influence the activity and plasticity of neurons and glial cells during early development, and they continue to exert trophic and protective effects in the adult nervous system. Steroids are produced by the gonads and adrenal glands(Figure 2) and reach the brain, the spinal cord and the peripheral nerves via the bloodstream. However, some of them, named neurosteroids, can also be synthesized within the nervous system. They include pregnenolone, progesterone, dehydroepiandrosterone and their reduced metabolites and sulfate esters. Little is known concerning the regulation of steroid synthesis in the nervous system, which involves interactions between different cell types. For example, the synthesis of progesterone by Schwann cells in peripheral nerves is regulated by a diffusible neuronal signal. Neurotrophic and neuroprotective effects of steroids have been documented both in cell culture and in vivo. PROG plays an important role in the neurological recovery from traumatic injury of the brain and spinal cord by mechanisms involving protection from excitotoxic cell death, lipid peroxydation and the induction of specific enzymes. After transection of the rat spinal cord, PROG increases the number of nitric oxide synthase expressing astrocytes immediately above and below the lesion. PROG also plays an important role in the formation of new myelin sheaths. This has been shown in the regenerating mouse sciatic nerve after lesion and in cocultures of sensory neurons and Schwann cells. PROG promotes myelination by activating the expression of genes coding for myelin proteins. The modulation of neurostransmitter receptors, in particular the type A -aminobutyric acid, the N-methyl-D-aspartate and the sigma 1 receptors, is involved in the psychopharmacological effects of steroids and allows to explain their anticonvulsant, anxiolytic, antidepressive and sedative effects as well as their influence on memory. Pregnenolone sulfate has been shown to reverse age-related deficits in spatial memory performance and to have protective effects on memory in different models of amnesia.
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