The brain synthesizes a variety of neurosteroids, including neuroestradiol. Inhibition of neuroestradiol synthesis results in alterations in basic neurodevelopmental processes, such as neurogenesis, neuroblast migration, neuritogenesis and synaptogenesis. Although the neurodevelopmental actions of neuroestradiol are exerted in both sexes, some of them are sex-specific, such as the well characterized effects of neuroestradiol derived from the metabolism of testicular testosterone during critical periods of male brain development. In addition, recent findings have shown sex-specific actions of neuroestradiol on neuroblast migration, neuritic growth and synaptogenesis in females. Among other factors, the epigenetic regulation exerted by X linked genes, such as Kdm6a/Utx, may determine sex-specific actions of neuroestradiol in the female brain. This review evidences the impact of neuroestradiol on brain formation in both sexes and highlights the interaction of neural steriodogenesis, hormones and sex chromosomes in sex-specific brain development.
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Neuroestradiol and neuronal development: Not an exclusive male tale anymore.
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The brain synthesizes a variety of neurosteroids, including neuroestradiol. Inhibition of neuroestradiol synthesis results in alterations in basic neurodevelopmental processes, such as neurogenesis, neuroblast migration, neuritogenesis and synaptogenesis. Although the neurodevelopmental actions of neuroestradiol are exerted in both sexes, some of them are sex-specific, such as the well characterized effects of neuroestradiol derived from the metabolism of testicular testosterone during critical periods of male brain development.
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BMC Neurosci
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Willis-Knighton Endowed Professor of Pharmacy and Director, School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, 356 Bienville Building, 1800 Bienville Drive, Monroe, LA, 71201, USA.
Background: Ventromedial hypothalamic nucleus (VMN) gluco-regulatory transmission is subject to sex-specific control by estradiol. The VMN is characterized by high levels of aromatase expression.
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Center for Neuroendocrine Studies, University of Massachusetts, Amherst, MA 01003, United States of America. Electronic address:
Decades of work have established the brain as a source of steroid hormones, termed 'neurosteroids'. The neurosteroid neuroestradiol is produced in discrete brain areas and influences cognition, sensory processing, reproduction, neurotransmission, and disease. A prevailing research focus on neuroestradiol has essentially ignored whether its immediate synthesis precursor - the androgen testosterone - is also dynamically regulated within the brain.
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Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, United States; Department of Pediatrics, University of Wisconsin, Madison, WI 53706, United States. Electronic address:
Contribution to Special Issue on Fast effects of steroids. The concept that the positive feedback effect of ovarian estradiol (E) results in GnRH and gonadotropin surges is a well-established principle. However, a series of studies investigating the rapid action of E in female rhesus monkeys has led to a new concept that neuroestradiol, synthesized and released in the hypothalamus, also contributes to regulation of the preovulatory GnRH surge.
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Am J Physiol Endocrinol Metab
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Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, Wisconsin.
Whereas the ovary produces the majority of estradiol (E) in mature female primates, extraovarian sources contribute to E synthesis and action, including the brain E-regulating hypothalamic gonadotropin-releasing hormone. In ovary-intact female rodent models, aromatase inhibition (AI) induces a polycystic ovary syndrome-like hypergonadotropic hyperandrogenism due to absent E-mediated negative feedback. To examine the role of extraovarian E on nonhuman primate gonadotropin regulation, the present study uses letrozole to elicit AI in adult female marmoset monkeys.
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