Impact of melatonin and molecular clockwork components on the expression of thyrotropin beta-chain (Tshb) and the Tsh receptor in the mouse pars tuberalis.
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 type 2 and 3 in the ependymal cell layer of the infundibular recess (EC) via TSH receptors (TSHRs). To analyze the impact of melatonin and the molecular clockwork on the expression of Tshb and Tshr, we investigated melatonin-proficient C3H wild-type (WT), melatonin receptor 1-deficient (MT1-/-) or clockprotein PERIOD1-deficient (mPER1-/-) mice. Expression of Tshb and TSHb immunoreactivity in PT were low during day and high during the night in WT, high during the day and low during the night in mPER1-deficient, and equally high during the day and night in MT1-deficient mice. Melatonin injections into WT acutely suppressed Tshb expression. Transcription assays showed that the 5' upstream region of the Tshb gene could be controlled by clockproteins. Tshr levels in PT were low during the day and high during the 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 phosphorylated cAMP response element-binding protein in PT and EC and deiodinase type 2 in the EC. Our data suggest that Tshb expression in PT is controlled by melatonin and the molecular clockwork and that melatonin activates Tshr expression in PT but not in EC. They also confirm the functional importance of TSHR in the PT and EC.
Unfried
Claudia
C
Emmy Noether-Nachwuchsgruppe, Institut für Anatomie II, Goethe-Universität, D-60590 Frankfurt/M, Germany.
Ansari
Nariman
N
Yasuo
Shinobu
S
Korf
Horst-Werner
HW
von Gall
Charlotte
C
D000818:Animals; D001683:Biological Clocks; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007453:Iodide Peroxidase / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D056950:Period Circadian Proteins; D044122:Receptor, Melatonin, MT1 / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism; D037322:Thyrotropin, beta Subunit / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
D017362:Cyclic AMP Response Element-Binding Protein; D047908:Intracellular Signaling Peptides and Proteins; D007453:Iodide Peroxidase; D008550:Melatonin; D056950:Period Circadian Proteins; D044122:Receptor, Melatonin, MT1; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D037322:Thyrotropin, beta Subunit; D014157:Transcription Factors; D000097564:Iodothyronine Deiodinase Type II; C492004:Creb1 protein, mouse; C539023:Per1 protein, mouse