Family members CREB and CREM control thyrotropin-releasing hormone (TRH) expression in the hypothalamus

Thyrotropin-releasing hormone (TRH) in the paraventricular nucleus (PVN) of the hypothalamus is regulated by thyroid hormone (TH). cAMP response element binding protein (CREB) has also been postulated to regulate TRH expression but its interaction with TH signaling in vivo is not known. To evaluate the role of CREB in TRH regulation in vivo, we deleted CREB from PVN neurons to generate the CREB1ΔSIM1 mouse. As previously shown, loss of CREB was compensated for by an up-regulation of CREM in euthyroid CREB1ΔSIM1 mice but TSH, T4 and T3 levels were normal, even though TRH mRNA levels were elevated. Interestingly, TRH mRNA expression was also increased in the PVN of CREB1ΔSIM1 mice in the hypothyroid state but became normal when made hyperthyroid. Importantly, CREM levels were similar in CREB1ΔSIM1 mice regardless of thyroid status, demonstrating that the regulation of TRH by T3in vivo likely occurs independently of the CREB/CREM family.

► Lack of CREB in PVN neurons leads to a significant increase of TRH expression.
► Lack of CREB in PVN neurons leads to a significant increase of CREM expression.
► Lack of CREB in PVN neurons does not affect regulation of TRH by thyroid hormones.
► CREM regulates TRH in vitro and in vivo.
► Regulation of TRH by T3 in vivo likely occurs independently of the CREB/CREM family.