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Nobuhiro Nakao

Bio: Nobuhiro Nakao is an academic researcher from Nagoya University. The author has contributed to research in topics: DIO2 & Deiodinase. The author has an hindex of 13, co-authored 17 publications receiving 1363 citations.

Papers
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Journal ArticleDOI
20 Mar 2008-Nature
TL;DR: Two waves of gene expression are identified in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone and increased TSH in the pars tuberalis seems to trigger long-day photoinduced seasonal breeding.
Abstract: Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid-hormone-activating enzyme (type 2 deiodinase, DIO2) in the mediobasal hypothalamus (MBH) of the Japanese quail (Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin (TSH) beta-subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular (ICV) administration of TSH to short-day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor-cyclic AMP (cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding.

467 citations

Journal ArticleDOI
TL;DR: It was found that expression of Dio2 in the mediobasal hypothalamus is induced by light and that T(3) content in the mediated hypothalamus increased under long day conditions and intracerebroventricular infusion of T( 3) mimics photoperiodically induced testicular growth.
Abstract: The molecular mechanisms responsible for seasonal time measurement have yet to be fully described. Recently, we used differential analysis to identify that the type 2 iodothyronine deiodinase (Dio2) gene is responsible for the photoperiodic response of gonads in Japanese quail. It was found that expression of Dio2 in the mediobasal hypothalamus is induced by light and that T(3) content in the mediobasal hypothalamus increased under long day conditions. In addition, we showed that intracerebroventricular infusion of T(3) mimics photoperiodically induced testicular growth. Because it is well known that thyroid hormone is also essential for the maintenance of the seasonal reproductive changes in a number of mammals, we examined expression of Dio2 in Djungarian hamsters and found expression in the ependymal cell layer lining the infralateral walls of the third ventricle and the cell-clear zone overlying the tuberoinfundibular sulcus. Signal intensity was high under long days and weak under short days. Although light pulse did not affect Dio2 expression, melatonin injections decreased Dio2 expression under long days. These results indicate that Dio2 may be involved in the regulation of seasonal reproduction in mammals in the same way as observed in birds.

151 citations

Journal ArticleDOI
TL;DR: These reciprocal changes in the two gene switches are the earliest events yet recorded in the photoinduction process, and overall, these reciprocal changes offer the potential to regulate active brain thyroid hormone concentrations rather precisely at the site in the brain wherephotoinduction is triggered.
Abstract: The molecular mechanisms underlying photoperiodic time measurement are not well understood in any organism. Relatively recently, however, it has become clear that thyroid hormones play an important role in photoperiodism, and in a previous study we reported that long daylengths in Japanese quail increase hypothalamic levels of T3 and of the thyroid hormone-activating enzyme, type 2 iodothyronine deiodinase. The present study extends these observations to measure gene levels of the thyroid hormone-inactivating enzyme, type 3 deiodinase. Levels decreased after exposure to long days, but increased under short days. Changes in the two genes were then analyzed during the precisely timed photoinduction that occurs in quail exposed to a single long day. The two gene switches are the earliest events yet recorded in the photoinduction process, and overall, these reciprocal changes offer the potential to regulate active brain thyroid hormone concentrations rather precisely at the site in the brain where photoinduct...

140 citations

Journal ArticleDOI
TL;DR: The expression of the clock genes, Per2 and Per3, Clock, and Bmal1 (brain and muscle Arnt-like protein 1), in preovulatory follicles in laying quail are demonstrated by demonstrating the timing of ovulation in poultry is controlled solely by a clock-dependent mechanism within the neuroendocrine system.
Abstract: It is now known that circadian clocks are localized not only in the central pacemaker but also in peripheral organs. An example of a clock-dependent peripheral organ is the ovary of domestic poultry in which ovulation is induced by the positive feedback action of ovarian progesterone on the neuroendocrine system to generate a preovulatory release of LH during a daily 6-10 h "open period" of the ovulatory cycle. It has been assumed previously that the timing of ovulation in poultry is controlled solely by a clock-dependent mechanism within the neuroendocrine system. Here, we question this assumption by demonstrating the expression of the clock genes, Per2 (Period 2) and Per3, Clock, and Bmal1 (brain and muscle Arnt-like protein 1), in preovulatory follicles in laying quail. Diurnal changes in Per2 and Per3 expression were seen in the largest preovulatory follicle (F1) but not in smaller follicles. We next sought to identify clock-driven genes in preovulatory follicles focusing on those involved in the synthesis of progesterone. One such gene was identified, encoding steroidogenic acute regulatory protein (StAR), which showed 24-h changes in expression in the F1 follicle coinciding with those of Per2. Evidence that StAR gene expression is clock driven was obtained by showing that its 5' flanking region contains E-box enhancers that bind to CLOCK/BMAL1 heterodimers to activate gene transcription. We also showed that LH administration increased the promoter activity of chicken StAR. We therefore suggest that the timing of ovulation in poultry involves an LH-responsive F1 follicular clock that is involved in the timing of the preovulatory release of progesterone.

128 citations

Journal ArticleDOI
TL;DR: This review aims to summarize the currently available knowledge on the interactions between elements of the thyroid hormone axis and the neuroendocrine system involved in seasonal reproduction.
Abstract: Many animals that breed seasonally measure the day length (photoperiod) and use these measurements as predictive information to prepare themselves for annual breeding. For several decades, thyroid hormones have been known to be involved in this biological process; however, their precise roles remain unknown. Recent molecular analyses have revealed that local thyroid hormone activation in the hypothalamus plays a critical role in the regulation of the neuroendocrine axis involved in seasonal reproduction in both birds and mammals. Furthermore, functional genomics analyses have revealed a novel function of the hormone thyrotropin. This hormone plays a key role in signaling day-length changes to the brain and thus triggers seasonal breeding. This review aims to summarize the currently available knowledge on the interactions between elements of the thyroid hormone axis and the neuroendocrine system involved in seasonal reproduction.

105 citations


Cited by
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Journal ArticleDOI
TL;DR: The SCN network synchronizes its component cellular oscillators, reinforces their oscillations, responds to light input by altering their phase distribution, increases their robustness to genetic perturbations, and enhances their precision.
Abstract: The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals. Individual SCN neurons in dispersed culture can generate independent circadian oscillations of clock gene expression and neuronal firing. However, SCN rhythmicity depends on sufficient membrane depolarization and levels of intracellular calcium and cAMP. In the intact SCN, cellular oscillations are synchronized and reinforced by rhythmic synaptic input from other cells, resulting in a reproducible topographic pattern of distinct phases and amplitudes specified by SCN circuit organization. The SCN network synchronizes its component cellular oscillators, reinforces their oscillations, responds to light input by altering their phase distribution, increases their robustness to genetic perturbations, and enhances their precision. Thus, even though individual SCN neurons can be cell-autonomous circadian oscillators, neuronal network properties are integral to normal function of the SCN.

1,045 citations

Journal ArticleDOI
25 Mar 2010-Nature
TL;DR: The authors used massively parallel sequencing to identify selective sweeps of favorable alleles and candidate mutations that have had a prominent role in the domestication of domestic chickens and their subsequent specialization into broiler (meat-producing) and layer (egg-consuming) chickens.
Abstract: Domestic animals are excellent models for genetic studies of phenotypic evolution They have evolved genetic adaptations to a new environment, the farm, and have been subjected to strong human-driven selection leading to remarkable phenotypic changes in morphology, physiology and behaviour Identifying the genetic changes underlying these developments provides new insight into general mechanisms by which genetic variation shapes phenotypic diversity Here we describe the use of massively parallel sequencing to identify selective sweeps of favourable alleles and candidate mutations that have had a prominent role in the domestication of chickens (Gallus gallus domesticus) and their subsequent specialization into broiler (meat-producing) and layer (egg-producing) chickens We have generated 445-fold coverage of the chicken genome using pools of genomic DNA representing eight different populations of domestic chickens as well as red jungle fowl (Gallus gallus), the major wild ancestor We report more than 7,000,000 single nucleotide polymorphisms, almost 1,300 deletions and a number of putative selective sweeps One of the most striking selective sweeps found in all domestic chickens occurred at the locus for thyroid stimulating hormone receptor (TSHR), which has a pivotal role in metabolic regulation and photoperiod control of reproduction in vertebrates Several of the selective sweeps detected in broilers overlapped genes associated with growth, appetite and metabolic regulation We found little evidence that selection for loss-of-function mutations had a prominent role in chicken domestication, but we detected two deletions in coding sequences that we suggest are functionally important This study has direct application to animal breeding and enhances the importance of the domestic chicken as a model organism for biomedical research

943 citations

Journal ArticleDOI
TL;DR: It seems clear that deiodinases play a much broader role than once thought, with great ramifications for the control of thyroid hormone signaling during vertebrate development and metamorphosis, as well as injury response, tissue repair, hypothalamic function, and energy homeostasis in adults.
Abstract: The iodothyronine deiodinases initiate or terminate thyroid hormone action and therefore are critical for the biological effects mediated by thyroid hormone. Over the years, research has focused on their role in preserving serum levels of the biologically active molecule T3 during iodine deficiency. More recently, a fascinating new role of these enzymes has been unveiled. The activating deiodinase (D2) and the inactivating deiodinase (D3) can locally increase or decrease thyroid hormone signaling in a tissue- and temporal-specific fashion, independent of changes in thyroid hormone serum concentrations. This mechanism is particularly relevant because deiodinase expression can be modulated by a wide variety of endogenous signaling molecules such as sonic hedgehog, nuclear factor-κB, growth factors, bile acids, hypoxia-inducible factor-1α, as well as a growing number of xenobiotic substances. In light of these findings, it seems clear that deiodinases play a much broader role than once thought, with great ramifications for the control of thyroid hormone signaling during vertebrate development and metamorphosis, as well as injury response, tissue repair, hypothalamic function, and energy homeostasis in adults.

715 citations

Journal ArticleDOI
20 Mar 2008-Nature
TL;DR: Two waves of gene expression are identified in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone and increased TSH in the pars tuberalis seems to trigger long-day photoinduced seasonal breeding.
Abstract: Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid-hormone-activating enzyme (type 2 deiodinase, DIO2) in the mediobasal hypothalamus (MBH) of the Japanese quail (Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin (TSH) beta-subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular (ICV) administration of TSH to short-day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor-cyclic AMP (cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding.

467 citations

Journal ArticleDOI
TL;DR: This review focuses on the neurodegenerative mechanisms and effects of Fe, Mn and Hg, addressing the main sources of exposure to these metals, their transport mechanisms into the brain, and therapeutic modalities to mitigate their neurotoxic effects.

446 citations