Thyrotrophin in the pars tuberalis triggers photoperiodic response
Nobuhiro NakaoHiroko OnoTakashi YamamuraTsubasa AnrakuTsuyoshi TakagiKumiko HigashiShinobu YasuoYasuhiro KatouSaburo KageyamaYumiko UnoTakeya KasukawaMasayuki IigoP. J. SharpAtsushi IwasawaYutaka SuzukiSumio SuganoTeruyuki NiimiMakoto MizutaniTakao NAMIKAWAShizufumi EbiharaHiroki R. UedaTakashi Yoshimura
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Pars tuberalis
DIO2
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.
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Pars tuberalis
Iodothyronine deiodinase
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Across taxa, the seasonal transition between non-breeding and breeding states is controlled by localised thyroid hormone signalling in the deep brain via reciprocal switching of deiodinase enzyme expression from type 3 (DIO3) to type 2 (DIO2). This reciprocal switch is considered to be mediated by increasing thyroid-stimulating hormone beta (TSH beta) release from the pars tuberalis, which occurs in response to a change in photoperiod. Although well characterised in a handful of model organisms in controlled laboratory settings, this pathway remains largely unexplored in free-living animals under natural environmental conditions. In this comparative gene expression study, we investigated hypothalamic thyroid hormone signalling in two seasonally breeding subspecies of white-crowned sparrow (Zonotrichia leucophrys), across the entirety of their annual cycles. The migratory Gambel's (Z. l. gambelii) and resident Nuttall's (Z. l. nuttalii) subspecies differ with respect to timing of reproduction, as well as life history stage and migratory strategies. Although DIO3 mRNA expression was elevated and DIO2 mRNA expression was reduced in the wintering period in both subspecies, DIO2 peaked in both subspecies prior to the onset of reproduction. However, there was differential timing between subspecies in peak DIO2 expression. Intriguingly, seasonal modulation of TSH beta mRNA was only observed in migrants, where expression was elevated at the start of breeding, consistent with observations from other highly photoperiodic species. There was no correlation between TSH beta, DIO2 and gonadotropin-releasing hormone-I mRNA or reproductive metrics in residents. Based on these observed differences, we discuss potential implications for our understanding of how changes in medial basal hypothalamic gene expression mediates initiation of seasonal reproduction.
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Recent studies have characterised a retrograde mechanism whereby the pineal hormone melatonin acts in the pars tuberalis (PT) of the pituitary gland to control thyroid hormone action in the hypothalamus, leading to changes in seasonal reproductive function. This involves the release of thyroid-stimulating hormone (TSH) from PT that activates type II deiodinase (DIO2) gene expression in hypothalamic ependymal cells, locally generating biologically active T3, and thus triggering a neuroendocrine cascade. In the present study, we investigated whether a similar regulatory mechanism operates in the European hamster. This species utilises both melatonin signalling and a circannual timer to time the seasonal reproductive cycle. We found that expression of betaTSH RNA in the PT was markedly increased under long compared to short photoperiod, whereas TSH receptor expression was localised in the ependymal cells lining the third ventricle, and in the PT, where its expression varied with time and photoperiod. In the ependymal cells at the base of the third ventricle, DIO2 and type III deiodinase (DIO3) expression was reciprocally regulated, with DIO2 activated under long and repressed under short photoperiod, and the reverse case for DIO3. These data are consistent with recent observations in sheep, and suggest that the PT TSH third ventricle-ependymal cell relay plays a conserved role in initiating the photoperiodic response in both long- and short-day breeding mammals.
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Iodothyronine deiodinase
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In many species living in temperate zones, reproduction is controlled by the photoperiod. Recent findings have clarified that type 2 iodothyronine deiodinase (Dio2) plays a significant role in the photoperiodic response of gonads in the mediobasal hypothalamus, converting the prohormone T(4) into bioactive T(3). In mammals, Dio2 expression is suppressed by long-term melatonin injections, although the signal transduction pathways that link the melatonin signal to Dio2 expression are unknown. As a first step to approach the problem, we have here investigated the temporal dynamics of the melatonin effect on Dio2 expression using male Syrian hamsters. Dio2 mRNA levels were found to show diurnal rhythms under long-day conditions in an area adjacent to the tuberoinfundibular sulcus and in the ependymal cell layer lining the ventrobasal walls of the third ventricle. Daily sc melatonin injections given in the late afternoon under long-day condition suppressed the Dio2 mRNA levels already at the first day after the onset of the treatment in the ependymal cell layer lining the ventrobasal walls of the third ventricle, and 1 d later in an area adjacent to the tuberoinfundibular sulcus. These suppressive effects were sustained for at least 2 d after a single injection. Furthermore, we examined the temporal changes of the Dio2 expression after the onset of the treatment, showing that the suppression did not occur until midday of the next day. These data suggest that melatonin is involved in the signal transduction mechanisms controlling the photoperiodic response of gonads by acting on Dio2 expression rather rapidly through indirect pathways.
Syrian hamsters
Mesocricetus
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Seasonal reproduction depends on photoperiod‐regulated activation or suppression of the gonadal axis. Recent studies in quail have identified long‐day induced TSH‐β expression in the pars tuberalis (PT) as a rapid trigger of gonadal activation. Thyroid‐stimulating hormone (TSH) induces type 2 deiodinase ( Dio2 ) in the ependymal cell layer (EC) of the infundibular recess to stimulate the gonadal axis. A similar mechanism is proposed in sheep and mice, but the experimental data on the temporal patterns of induction and suppression of TSH‐β and Dio2 expression are incomplete. In the present study, we examined the expression of TSH‐β and Dio2 in hamsters transferred from short‐ to long‐day conditions for 9 days, and demonstrate the induction of TSH‐β and Dio2 on day 8 after transition. These data demonstrate the close relationship between TSH‐β and Dio2 expression in the inductive pathway. The temporal expression of TSH‐β and Dio2 in the suppressive pathway was also examined by s.c. melatonin injection, which mimics the transition from long to short days. Importantly, Dio2 expression in the EC is suppressed on day 1 after the onset of injection, whereas TSH‐β expression in the PT was not suppressed until day 10. These data suggest that regulated transcription of TSH‐β is involved in the induction of the gonadal axis in mammals, whereas the suppression of this axis is mediated by different mechanisms.
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Iodothyronine deiodinase
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Melatonin transmits photoperiodic signals that regulate reproduction. Two melatonin receptors (MT1 and MT2) have been cloned in mammals and additional melatonin binding sites suggested, but the receptor that mediates the effects of melatonin on the photoperiodic gonadal response has not yet been identified. We therefore investigated in mice whether and how targeted disruption of MT1, MT2, or both receptor types affects the expression level of two key genes for the photoperiodic gonadal regulation, type 2 and 3 deiodinase ( Dio2 and Dio3 , respectively). These are expressed in the ependymal cell layer lining the infundibular recess of the third ventricle and regulated by thyrotropin produced in the pars tuberalis. In wild-type C3H mice, Dio2 expression was constantly low, and no photoperiodic changes were observed, whereas Dio3 expression was upregulated under short-day conditions. In C3H with targeted disruption of MT1 and MT1/MT2, Dio2 expression was constitutively upregulated, Dio3 expression was constitutively downregulated, and the photoperiodic effect on Dio3 expression was abolished. Under short-day conditions, C3H with targeted disruption of MT2 displayed similar expression levels of Dio2 and Dio3 as wild-type animals, but they responded to long-day condition with a stronger suppression of Dio3 than wild-type mice. Melatonin injections into wild-type C57BL mice suppressed Dio2 expression and induced Dio3 expression under long-day conditions. These effects were abolished in C57BL mice with targeted disruption of MT1. All data suggest that the melatonin signal that transmits photoperiodic information to the hypothalamo–hypophysial axis acts on the MT1 receptor.
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Abstract Across taxa, the seasonal transition between non‐breeding and breeding states is controlled by localised thyroid hormone signalling in the deep brain via reciprocal switching of deiodinase enzyme expression from type 3 (DIO3) to type 2 (DIO2). This reciprocal switch is considered to be mediated by increasing thyroid‐stimulating hormone β (TSHβ) release from the pars tuberalis, which occurs in response to a change in photoperiod. Although well characterised in a handful of model organisms in controlled laboratory settings, this pathway remains largely unexplored in free‐living animals under natural environmental conditions. In this comparative gene expression study, we investigated hypothalamic thyroid hormone signalling in two seasonally breeding subspecies of white‐crowned sparrow ( Zonotrichia leucophrys ), across the entirety of their annual cycles. The migratory Gambel's ( Z . l . gambelii ) and resident Nuttall's ( Z . l . nuttalii ) subspecies differ with respect to timing of reproduction, as well as life history stage and migratory strategies. Although DIO3 mRNA expression was elevated and DIO2 mRNA expression was reduced in the wintering period in both subspecies, DIO2 peaked in both subspecies prior to the onset of reproduction. However, there was differential timing between subspecies in peak DIO2 expression. Intriguingly, seasonal modulation of TSHβ mRNA was only observed in migrants, where expression was elevated at the start of breeding, consistent with observations from other highly photoperiodic species. There was no correlation between TSHβ, DIO2 and gonadotropin‐releasing hormone‐I mRNA or reproductive metrics in residents. Based on these observed differences, we discuss potential implications for our understanding of how changes in medial basal hypothalamic gene expression mediates initiation of seasonal reproduction.
DIO2
Pars tuberalis
Iodothyronine deiodinase
Subspecies
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Citations (8)
Across taxa, the seasonal transition between non-breeding and breeding states is controlled by localised thyroid hormone signalling in the deep brain via reciprocal switching of deiodinase enzyme expression from type 3 (DIO3) to type 2 (DIO2). This reciprocal switch is considered to be mediated by increasing thyroid-stimulating hormone beta (TSH beta) release from the pars tuberalis, which occurs in response to a change in photoperiod. Although well characterised in a handful of model organisms in controlled laboratory settings, this pathway remains largely unexplored in free-living animals under natural environmental conditions. In this comparative gene expression study, we investigated hypothalamic thyroid hormone signalling in two seasonally breeding subspecies of white-crowned sparrow (Zonotrichia leucophrys), across the entirety of their annual cycles. The migratory Gambel's (Z. l. gambelii) and resident Nuttall's (Z. l. nuttalii) subspecies differ with respect to timing of reproduction, as well as life history stage and migratory strategies. Although DIO3 mRNA expression was elevated and DIO2 mRNA expression was reduced in the wintering period in both subspecies, DIO2 peaked in both subspecies prior to the onset of reproduction. However, there was differential timing between subspecies in peak DIO2 expression. Intriguingly, seasonal modulation of TSH beta mRNA was only observed in migrants, where expression was elevated at the start of breeding, consistent with observations from other highly photoperiodic species. There was no correlation between TSH beta, DIO2 and gonadotropin-releasing hormone-I mRNA or reproductive metrics in residents. Based on these observed differences, we discuss potential implications for our understanding of how changes in medial basal hypothalamic gene expression mediates initiation of seasonal reproduction.
DIO2
Pars tuberalis
Iodothyronine deiodinase
Subspecies
Cite
Citations (0)
Across taxa, the seasonal transition between non-breeding and breeding states is controlled by localised thyroid hormone signalling in the deep brain via reciprocal switching of deiodinase enzyme expression from type 3 (DIO3) to type 2 (DIO2). This reciprocal switch is considered to be mediated by increasing thyroid-stimulating hormone beta (TSH beta) release from the pars tuberalis, which occurs in response to a change in photoperiod. Although well characterised in a handful of model organisms in controlled laboratory settings, this pathway remains largely unexplored in free-living animals under natural environmental conditions. In this comparative gene expression study, we investigated hypothalamic thyroid hormone signalling in two seasonally breeding subspecies of white-crowned sparrow (Zonotrichia leucophrys), across the entirety of their annual cycles. The migratory Gambel's (Z. l. gambelii) and resident Nuttall's (Z. l. nuttalii) subspecies differ with respect to timing of reproduction, as well as life history stage and migratory strategies. Although DIO3 mRNA expression was elevated and DIO2 mRNA expression was reduced in the wintering period in both subspecies, DIO2 peaked in both subspecies prior to the onset of reproduction. However, there was differential timing between subspecies in peak DIO2 expression. Intriguingly, seasonal modulation of TSH beta mRNA was only observed in migrants, where expression was elevated at the start of breeding, consistent with observations from other highly photoperiodic species. There was no correlation between TSH beta, DIO2 and gonadotropin-releasing hormone-I mRNA or reproductive metrics in residents. Based on these observed differences, we discuss potential implications for our understanding of how changes in medial basal hypothalamic gene expression mediates initiation of seasonal reproduction.
DIO2
Pars tuberalis
Iodothyronine deiodinase
Subspecies
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Mus musculus molossinus (MSM) is a wild-derived mouse strain which maintains the ability to synthesize melatonin in patterns reflecting the ambient photoperiod. The objective of this study was to characterize the effects of photoperiodic variation on metabolic and reproductive traits, and the related changes in pituitary-hypothalamic gene expression in MSM mice. MSM mice were kept in long (LP) or short photoperiod (SP) for 6 weeks. Our results demonstrate that MSM mice kept in LP, as compared to mice kept in SP, display higher expression of genes encoding thyrotropin (TSH) in the pars tuberalis, thyroid hormone deiodinase 2 (dio2) in the tanycytes, RFamide-related peptide (RFRP3) in the hypothalamus and lower expression of dio3 in the tanycytes, along with larger body and reproductive organ mass. Additionally, to assess the effects of the gestational photoperiodic environment on the expression of these genes, we kept MSM mice in LP or SP from gestation and studied offspring. We show that the gestational photoperiod affects the TSH/dio pathway in newborn MSM mice in a similar way to adults. This result indicates a transgenerational effect of photoperiod from the mother to the fetus in utero. Overall, these results indicate that photoperiod can influence neuroendocrine regulation in a melatonin-proficient mouse strain, in a manner similar that documented in other seasonal rodent species. MSM mice may therefore become a useful model for research into the molecular basis of photoperiodic regulation of seasonal biology.
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Iodothyronine deiodinase
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