title: Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats.
abstract: We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 μL); DHT (dihydrotestosterone of 1.0 mg/50 μL); EV (estradiol valerate of 0.1 mg/50 μL); and control (sesame oil of 50 μL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area.
authors.affiliation: Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile.
authors.forename: Pedro
authors.initials: P
authors.lastname: Espinosa
authors.affiliation: Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile.
authors.forename: Roxana A
authors.initials: RA
authors.lastname: Silva
authors.affiliation: Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile.
authors.forename: Nicole K
authors.initials: NK
authors.lastname: Sanguinetti
authors.affiliation: Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile.
authors.forename: Francisca C
authors.initials: FC
authors.lastname: Venegas
authors.affiliation: Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile.
authors.forename: Raul
authors.initials: R
authors.lastname: Riquelme
authors.affiliation: Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile; Laboratorio de Neurogenética, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile.
authors.forename: Luis F
authors.initials: LF
authors.lastname: González
authors.affiliation: Laboratorio de Alteraciones Reproductivas y Metabólicas, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Cruz
authors.affiliation: Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile.
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Renard
authors.affiliation: Laboratorio de Neurogenética, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile.
authors.forename: Pablo R
authors.initials: PR
authors.lastname: Moya
authors.affiliation: Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, Chile.
authors.forename: Ramón
authors.initials: R
authors.lastname: Sotomayor-Zárate
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D013196:Dihydrotestosterone / Q000008:administration & dosage; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D012739:Gonadal Steroid Hormones / Q000008:administration & dosage*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D043343:Testosterone Propionate / Q000008:administration & dosage; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D004958:Estradiol; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D043343:Testosterone Propionate