Local control of thyroid hormone action during ontogeny of the song control system

The song control system of zebra finches (Taeniopygia guttata) develops in a sexually differentiated manner during song learning. While the influence of several major hormones like testosterone has been studied, thyroid hormones (THs) –a major factor in neural development– have been mostly overlooked. We therefore analysed by in situ hybridisation the expression of regulators of TH action: the deiodinases type 2 (DIO2) and 3 (DIO3), TH transporters monocarboxylate transporter 8 (MCT8), MCT10, organic anion transporting polypeptide 1C1 (OATP1C1) and large amino acid transporter 1 (LAT1), and TH receptors alpha (THRA) and beta (THRB), in male and female zebra finch brains between 10 and 120 days post hatch (dph), covering the sensory (20-60 dph), sensorimotor (30-90 dph) and crystallisation phase (90-120 dph) of song learning. In both sexes MCT8, LAT1, DIO2 and THRA showed high and widespread expression at 10-20 dph, which is the period of overall rapid brain growth, decreasing rapidly thereafter. DIO3, OATP1C1 and MCT10 were only found in the choroid plexus, while THRB expression was low at 10 dph and subsequently rising. However, male-specific expression patterns were observed at 30-60 dph, when DIO2 was highly expressed in endothelial cells in the song control nuclei Area X, HVC and RA of males only, but not in the surrounding tissue. This coincided with a large increase of vascularisation in RA but not in the other nuclei. Additionally, during the same period LAT1 expression was specifically increased in male HVC while THRB expression was increased in male and female RA. Based on these sex-, time- and location-specific expression patterns we suggest that THs play a major role in male song control nuclei development during both the sensory and sensorimotor phase of song learning, with the TH-activating DIO2 probably functioning as the main instigator.status: publishe