title: Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction.
abstract: The pituitary gland releases hormones in a pulsatile fashion guaranteeing signalling efficiency. The determinants of pulsatility are poorly circumscribed. Here we show in magnocellular hypothalamo-neurohypophyseal oxytocin (OT) neurons that the bursting activity underlying the neurohormonal pulses necessary for parturition and the milk-ejection reflex is entirely driven by a female-specific central pattern generator (CPG). Surprisingly, this CPG is active in both male and female neonates, but is inactivated in males after the first week of life. CPG activity can be restored in males by orchidectomy or silenced in females by exogenous testosterone. This steroid effect is aromatase and caspase dependent, and is mediated via oestrogen receptor-α. This indicates the apoptosis of the CPG network during hypothalamic sexual differentiation, explaining why OT neurons do not burst in adult males. This supports the view that stereotypic neuroendocrine pulsatility is governed by CPGs, some of which are subjected to gender-specific perinatal programming.
authors: 1] INSERM, U862, Neurocentre Magendie, F-33077 Bordeaux, France [2] Université de Bordeaux, F-33077 Bordeaux, France.
authors: Jean-Marc
authors: JM
authors: Israel
authors: 1] INSERM, U862, Neurocentre Magendie, F-33077 Bordeaux, France [2] Université de Bordeaux, F-33077 Bordeaux, France.
authors: Jean-Marie
authors: JM
authors: Cabelguen
authors: 1] INSERM, U862, Neurocentre Magendie, F-33077 Bordeaux, France [2] Université de Bordeaux, F-33077 Bordeaux, France.
authors: Gwendal
authors: G
authors: Le Masson
authors: 1] INSERM, U862, Neurocentre Magendie, F-33077 Bordeaux, France [2] Université de Bordeaux, F-33077 Bordeaux, France.
authors: Stéphane H
authors: SH
authors: Oliet
authors: 1] INSERM, U862, Neurocentre Magendie, F-33077 Bordeaux, France [2] Université de Bordeaux, F-33077 Bordeaux, France.
authors: Philippe
authors: P
authors: Ciofi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001141:Aromatase / Q000187:drug effects / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D063226:Central Pattern Generators / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D010121:Oxytocin / Q000187:drug effects / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012098:Reproduction; D012733:Sex Differentiation; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D047628:Estrogen Receptor alpha; D013739:Testosterone; D010121:Oxytocin; D001141:Aromatase; D020169:Caspases