The molecular mechanism underlying photoperiodism is not well understood in any organism. Long-day-induced conversion of prohormone T4 to bioactive T3 within the mediobasal hypothalamus (MBH) is critical for the photoperiodic regulation of reproduction. However, because thyroidectomy does not completely block the photoperiodic response in some species, the existence of a thyroid hormone-independent regulatory mechanism appears certain. To identify this novel mechanism, differential subtractive hybridization analysis was performed using MBH of quail kept under short-day and long-day conditions. This analysis identified a gene encoding TGFα. Expression of TGFα mRNA was induced in the median eminence by the stimulus of long days, and this induction was observed at dusk on the first long day. This rapid induction of TGFα mRNA was similar to induction of the thyroid hormone-activating enzyme gene [Dio2 (type 2 iodothyronine deiodinase)], which is the earliest event yet determined in the photoinduction process. Expression analysis of epidermal growth factor receptors revealed strong expression of erbB4 and weak expression of erbB1 and erbB2 in the median eminence. Intracerebroventricular infusion of physiological dose of TGFα induced LH secretion and testicular growth under short-day conditions. Finally, we demonstrate that T3 implantation and TGFα infusion into the MBH, either of which causes testicular growth, do not affect the expression of TGFα and Dio2, respectively. Thus, long-day-induced activation of the TGFα signaling pathway appears to mediate a thyroid hormone-independent pathway for the photoperiodic regulation of reproduction.
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