Impact of Melatonin and Molecular Clockwork Components on the Expression of Thyrotropin Beta Chain (Tshb) and the Tsh Receptor in the Mouse Pars Tuberalis

Abstract

Photoperiodic regulation of reproduction in birds and mammals involves thyrotropin beta chain (TSHb) which is secreted from the pars tuberalis (PT) and controls the expression of deiodinase typ 2 (Dio2) and 3 (Dio3) in the ependymal cell layer of the infundibular recess (EC) via TSH receptors (TSHR). To analyze the impact of melatonin and the molecular clockwork on the expression of Tshb and Tshr we investigated melatonin proficient C3H wildtype (WT), melatonin receptor 1 (MT1) and mPER1-deficient mice. Expression of Tshb and TSHb immunoreactivity in PT were low during day and high during night in WT, high during day and low during night in mPER1-deficient and equally high during day and night in MT1-deficient mice. Melatonin injections into WT acutely suppressed Tshb expression. Transcription assays showed that mPER1 significantly reduced the CLOCK:BMAL1-induced transcription of the Tshb. Tshr levels in PT were low during day and high during night in WT and mPER1-deficient mice and equally low in MT1-deficient mice. Tshr expression in the EC did not show a day/night variation. Melatonin injections into WT acutely induced Tshr expression in PT, but not in EC. TSH stimulation of hypothalamic slice cultures of WT induced pCREB in PT and EC and Dio2 in the EC. Our data suggest that 1) Tshb expression in PT is controlled by melatonin and the molecular clockwork and 2) melatonin activates Tshr expression in PT, but not in EC. They also confirm the functional importance of TSHR in the PT and EC.