title: Steroidogenesis in the human brain: trends on sexual dimorphism
title: Steroidogenesi nel cervello umano: tendenze del dimorfismo sessuale
titleType: AlternativeTitle
Creators: name: AGRAPART, VINCENT
Publisher: name: Università degli Studi di Roma "Tor Vergata"
Year: 2009
Subjects: subject: neurosteroidi; espressione genica; SNC umano; dimorfismo sessuale; enzimi; GABA; neuromodulazione; qPCR
subject: neurosteroidi
subject: espressione genica
subject: SNC umano
subject: dimorfismo sessuale
subject: enzimi
subject: GABA
subject: neuromodulazione
subject: qPCR

description: 20. ciclo
description: I. The Metabolites of Sex and Stress Hormones are Neuroactive - 1. Biosynthesis of Neurosteroids - 1.1 P450 scc (Cholesterol side-chain cleavage enzyme, CYP11A1) - 1.2 Star (Steroidogenic acute regulatory protein) - 1.3 TSPO (Tanslocator protein 18 KDa) - 1.4 Sulfotransferases &amp; Sulfatase - A. SULT1A1 &amp; SULT1E1 - B. SULT2A1 &amp; SULT2B1 (a &amp; b) - C. Sulfatase (STS) - 1.5 Cytochrome P450c17 (CYP17A1) - 1.6 3β-hydroxysteroid dehydrogenase (3β-HSDs - 1.7 Cytochrome P450c21 (CYP21A2) - 1.8 Cytochrome P450c11B (CYP11B1 &amp; B2) - 1.9 11β-Hydroxysteroid dehydrogenases (11β-HSDs) - 1.10 5α-Reductase (5α-red-1,2) - 1.11 17β-hydroxysteroid dehydrogenase (17β-HSD) - A. 17β -HSD1 - B. 17β –HSD2 - C. 17β –HSD3 - D. 17β –HSD4 - E. 17β –HSD6 (RODH: retinoid dehydrogenases) - F. 17β-HSD7 - G. 17β-HSD8 - H. 17β-HSD10 - I. 17β-HSD11 (Pan1b, retSDR) - J. 17β-HSD12 - 1.12 Aldo-keto reductase : AKR1C1, AKR1C2, AKR1C3, AKR1C4 &amp; AKR1D1 - A. AKR1C1 (20α-Hydroxysteroid dehydrogenase) - B. AKR1C2 (3α-Hydroxysteroid dehydrogenase type 3, 3α-HSD3) - C. AKR1C3 (3α-Hydroxysteroid dehydrogenase type 2, 3α-HSD2, 17β-HSD5) - D. AKR1C4 (3α-Hydroxysteroid dehydrogenase type 1, 3α-HSD1) - E. AKR1D1 (5β-reductase) - F. Steroidogenic AKR1C members in the brain - 1.13 POR (cytochrome P450 oxidoreductase) - 1.14 P450 aromatase (CYP19A1) - A. Distribution of brain aromatase - B. Regulation of brain aromatase - C. Role of aromatase for testosterone negative feedback of LH - D. Regulation of behavior, mental state and memory - E. Regulation of brain plasticity - F. Neuroprotection and aromatase. - 2. Steroid receptors - 2.1 Androgen receptor (AR) - 2.2 Estrogens receptors (ERα and ERβ) - 2.3 Progesterone receptor (PGR, PR, NR3C3) - 2.4 Mineralocorticoid receptors (MR, NR3C2) and glucocorticoid receptors (GR, NR3C1). - 3. Receptors modulated by neurosteroids - 3.1 OPRS1 (σ receptor) - 3.2 N-methyl-D-aspartate (NMDA) receptor (NR1, GRIN1) - 3.3 The GABAA Receptor - A. GABAA receptors isoforms - B. Synaptic and Extrasynaptic GABAA Receptors - 3.4 The Effect of Neurosteroids on the GABAA Receptor - A. Synaptic Effect of Neurosteroids - B. Extrasynaptic Effect of Neurosteroids - C. GABAA Receptor Subunit Dependence of Neurosteroid Action - 3.5 Antagonist Neurosteroids on the GABAA Receptor - A. Mechanism of Pregnenolone Sulfate and other Sulfated Steroids - B. 3β-OH Steroid as GABAA Receptor Antagonist - 3.6 Neurosteroids and Behavior. - II. Human brain - 1. Cerebellum - 2. Caudate nucleus - 3. Frontal lobe - 4. Occipital lobe - 5. Parietal lobe - 6. Cingulate gyrus - 7. Thalamus - 8. White matter - 9. Neurosteoidogenesis in brain cells - 9.1 Astrocytes - 9.2 Oligodendrocytes and Schwann cells - 9.3 Neurons. - III. Sexual dimorphism - MATERIAL &amp; METHODS - RESULTS &amp; DISCUSSION - I. Endogenous Controls (EC) determination - II. Overview - 1. Cholesterol metabolites and transport - 2. Progesterone synthesis and metabolites - 2.1 Progesterone receptor (PGR, PR, NR3C3) - 2.2 3β-HSD and P450c17 - 2.3 AKRC family and progesterone metabolites - 3. Corticosteroids formation - 4. Steroid sulfatase and sulfuryl transferase in the human brain - 5. Sexual hormones - 5.1 Enzymes - 5.2 Sexual receptors - 6. 17β-hydroxysteroid dehydrogenase (17β -HSD - 7. GABAA Receptors. - III. Local peripheral transformation as main source of steroid hormones in the human brain . - IV. Sexual dimorphism in the human thalamus: Two sex dependant modulations pathways. - V. The human cerebellum: a predominant role in the neurosteroids formation?