Journal of neuroendocrinology
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J. Neuroendocrinol. · Apr 2007
Multicenter StudySex differences in the chloride cotransporters, NKCC1 and KCC2, in the developing hypothalamus.
In immature neurones, high basal [Cl(-)](i) results in membrane depolarisation following GABA(A) receptor activation, which is critical for various developmental processes including steroid-mediated sexual differentiation of the hypothalamus. Previously, we demonstrated that oestradiol enhances GABA-mediated Ca(2+) influx in neonate hypothalamus and that Ca(2+) induced activation of the transcription factor, cyclicAMP response element binding protein (CREB), was higher in male (high oestradiol) relative to female neonate hypothalamus. Based on these results, we hypothesised that expression of developmentally regulated chloride cotransporters may be sexually dimorphic. ⋯ By contrast, KCC2 mRNA levels were significantly lower in males relative to females on PND0. KCC2 protein was not detectable on ED20 or PND0 but was significantly lower in males relative to females on PND5. These results suggest a complex relationship between KCC2 and NKCC1 mRNA and protein in developing brain that is not easily linked to regulation by oestradiol.