Sexual Differentiation of the Brain Requires Perinatal Kisspeptin-GnRH Neuron Signaling
| Autor: | Jenny Clarkson, Günther Schütz, Nancy M. Sherwood, Ellen R. Busby, Allan E. Herbison, Milen Kirilov |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Sex Differentiation Tyrosine 3-Monooxygenase Vasopressins Population Hypothalamic–pituitary–gonadal axis Biology Receptors G-Protein-Coupled Gonadotropin-Releasing Hormone Mice Kisspeptin Pregnancy Internal medicine medicine Animals Testosterone education Receptor Mice Knockout Neurons GnRH Neuron Sex Characteristics education.field_of_study Sexual differentiation General Neuroscience Articles Preoptic Area Preoptic area Endocrinology Animals Newborn Female Receptors LHRH hormones hormone substitutes and hormone antagonists Receptors Kisspeptin-1 Signal Transduction |
| Zdroj: | The Journal of Neuroscience. 34:15297-15305 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3061-14.2014 |
| Popis: | Sex differences in brain function underlie robust differences between males and females in both normal and disease states. Although alternative mechanisms exist, sexual differentiation of the male mammalian brain is initiated predominantly by testosterone secreted by the testes during the perinatal period. Despite considerable advances in understanding how testosterone and its metabolite estradiol sexually differentiate the brain, little is known about the mechanism that generates the male-specific perinatal testosterone surge. In mice, we show that a male-specific activation of GnRH neurons occurs 0–2 h following birth and that this correlates with the male-specific surge of testosterone occurring up to 5 h after birth. The necessity of GnRH signaling for the sexually differentiating effects of the perinatal testosterone surge was demonstrated by the persistence of female-like brain characteristics in adult male, GnRH receptor knock-out mice. Kisspeptin neurons have recently been identified to be potent, direct activators of GnRH neurons. We demonstrate that a population of kisspeptin neurons appears in the preoptic area of only the male between E19 and P1. The importance of kisspeptin inputs to GnRH neurons for the process of sexual differentiation was demonstrated by the lack of a normal neonatal testosterone surge, and disordered brain sexual differentiation of male mice in which the kisspeptin receptor was deleted selectively from GnRH neurons. These observations demonstrate the necessity of perinatal GnRH signaling for driving brain sexual differentiation and indicate that kisspeptin inputs to GnRH neurons are essential for this process to occur. |
| Databáze: | OpenAIRE |
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