title: Hypophysectomy abolishes rhythms in rat thyroid hormones but not in the thyroid clock.
abstract: The endocrine body rhythms including the hypothalamic-pituitary-thyroid axis seem to be regulated by the circadian timing system, and daily rhythmicity of circulating thyroid-stimulating hormone (TSH) is well established. The circadian rhythms are generated by endogenous clocks in the central brain oscillator located in the hypothalamic suprachiasmatic nucleus (SCN) as well as multiple peripheral clocks, but information on the existence and function of a thyroid clock is limited. The molecular machinery in all clock cells is composed of a number of clock genes and their gene products are connected by autoregulatory feedback loops. Here, we provide evidence for a thyroid clock in the rat by demonstrating 24-h antiphase oscillations for the mRNA of the canonical clock genesPer1andBmal1, which was unaffected by hypophysectomy. By immunostaining, we supported the existence of a core oscillator in the individual thyroid cells by demonstrating a daily cytoplasmatic-nuclear shuttling of PER1 protein. In normal rats, we found a significant daily rhythmicity in the circulating thyroid hormones preceded by a peak in TSH. In hypophysectomised rats, although the thyroid clock was not affected, the oscillations in circulating thyroid hormones were abolished and the levels were markedly lowered. No daily oscillations in the expression of TSH receptor mRNA were observed in neither control rats nor hypophysectomised rats. Our findings indicate that the daily rhythm of thyroid hormone secretion is governed by SCN signalling via the rhythmic TSH secretion rather than by the local thyroid clock, which was still ticking after hypophysectomy.
authors.affiliation: Department of Clinical BiochemistryBispebjerg and Frederiksberg Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark jan.fahrenkrug@regionh.dk.
authors.forename: J
authors.initials: J
authors.lastname: Fahrenkrug
authors.affiliation: Department of Clinical BiochemistryBispebjerg and Frederiksberg Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Georg
authors.affiliation: Department of Clinical BiochemistryBispebjerg and Frederiksberg Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Hannibal
authors.affiliation: Department of Clinical BiochemistryBispebjerg and Frederiksberg Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: H L
authors.initials: HL
authors.lastname: Jørgensen
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D007016:Hypophysectomy / Q000379:methods*; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013961:Thyroid Gland / Q000502:physiology*; D013974:Thyroxine / Q000502:physiology*; D014284:Triiodothyronine / Q000502:physiology*
chemical_list: D056930:ARNTL Transcription Factors; C000598703:Arntl protein, rat; C539024:Per1 protein, rat; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D014284:Triiodothyronine; D013974:Thyroxine
keywords: HPT axis; circadian rhythms; clock genes; pituitary; thyroid hormones