RESUMO
The aim of the present study was to determine the developmental pattern of progesterone metabolism in rat brain and spinal cord from embryonic day 13 (E13) to the perinatal period. A marked decrease in the 5alpha-reduction of progesterone in brain cortex was observed between E13 and postnatal day 5 (P5). Isopregnanolone was the predominant isomer in E13 in both cortex and spinal cord and its synthesis diminished gradually, while the concentration of allopregnanolone did not change significantly during development. The placental tissue was able to synthesize the 3alpha and 3beta isomers in E13, E16 and E19 embryos with allopregnanolone being the major metabolite in all the samples. We conclude that embryonic central nervous system tissues are able to synthesize neurosteroids at least from stage E13 and that they are developmentally regulated.
Assuntos
Sistema Nervoso Central/embriologia , Sistema Nervoso Central/enzimologia , Placenta/enzimologia , Pregnanolona/biossíntese , Progesterona/biossíntese , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Animais , Radioisótopos de Carbono , Cromatografia em Camada Fina , Feminino , Masculino , Gravidez , Progesterona/análise , Progesterona/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The allosteric modulation of GABAA receptors in the rat brain cortex by neurosteroids was studied at different developmental stages. GABAA receptors were identified using [3H]muscimol binding to membrane preparations obtained from embryos and neonates (postnatal day 0-PN0; postnatal day 5-PN5). Data analysis disclosed a unique population of binding sites at all ages tested. An increase in the number of receptors was observed during development reaching almost adult levels at PN5. The neurosteroids pregnanolone and allopregnanolone failed to modulate [3H]muscimol specific binding in embryos and neonates, but a positive modulation was obtained in 5-day old animals. The addition of 1 microM pregnanolone induced a 3-6-fold increase [3H]muscimol affinity in PN5 (n = 3; P < 0.03), and a 2-fold increase in receptors number in adults (n = 3; P < 0.03). The differences observed in allosteric modulation during development suggest that a change occurred during the first week of life, and this change might affect GABAA receptor function.