Thyroid hormone activation of retinoic acid synthesis in hypothalamic tanycytes

Stoney, Patrick N.; Helfer, Gisela; Rodrigues, Diana; Morgan, Peter J.; McCaffery, Peter

doi:10.1002/glia.22938

Cited by 24 publications

(23 citation statements)

References 67 publications

(109 reference statements)

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“…In F344 rats, this includes retinoic acid signalling genes and proteins involved in uptake (Stra6, Ttr and Crbp1), synthesis (Raldh1, Raldh2), receptor response (RAR) and ligand clearance (Crapb1 and Cyp26B1). 54 Consistent with this, T3 Crpb1, Crabp2, RAR and RXR are all strongly regulated by photoperiod, with high expression under long days and much reduced expression under short days.…”

Section: The Role Of the Retinoic Acid Systemsupporting

confidence: 65%

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A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals

Helfer

Barrett

Morgan

2019

J Neuroendocrinology

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Animals have evolved diverse seasonal variations in physiology and reproduction to accommodate yearly changes in environmental and climatic conditions. These changes in physiology are initiated by changes in photoperiod (daylength) and are mediated through melatonin, which relays photoperiodic information to the pars tuberalis of the pituitary gland. Melatonin drives thyroid‐stimulating hormone transcription and synthesis in the pars tuberalis, which, in turn, regulates thyroid hormone and retinoic acid synthesis in the tanycytes lining the third ventricle of the hypothalamus. Seasonal variation in central thyroid hormone signalling is conserved among photoperiodic animals. Despite this, different species adopt divergent phenotypes to cope with the same seasonal changes. A common response amongst different species is increased hypothalamic cell proliferation/neurogenesis in short photoperiod. That cell proliferation/neurogenesis may be important for seasonal timing is based on (i) the neurogenic potential of tanycytes; (ii) the fact that they are the locus of striking seasonal morphological changes; and (iii) the similarities to mechanisms involved in de novo neurogenesis of energy balance neurones. We propose that a decrease in hypothalamic thyroid hormone and retinoic acid signalling initiates localised neurodegeneration and apoptosis, which leads to a reduction in appetite and body weight. Neurodegeneration induces compensatory cell proliferation from the neurogenic niche in tanycytes and new cells are born under short photoperiod. Because these cells have the potential to differentiate into a number of different neuronal phenotypes, this could provide a mechanistic basis to explain the seasonal regulation of energy balance, as well as reproduction. This cycle can be achieved without changes in thyroid hormone/retinoic acid and explains recent data obtained from seasonal animals held in natural conditions. However, thyroid/retinoic acid signalling is required to synchronise the cycles of apoptosis, proliferation and differentiation. Thus, hypothalamic neurogenesis provides a framework to explain diverse photoperiodic responses.

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Section: The Role Of the Retinoic Acid Systemsupporting

confidence: 65%

“…54 In F344 rats, the large changes in Raldh1 mRNA seen in response to photoperiod leads to an increase in tissue levels of retinoic acid in the hypothalamus. 54 In F344 rats, the large changes in Raldh1 mRNA seen in response to photoperiod leads to an increase in tissue levels of retinoic acid in the hypothalamus.…”

Section: The Role Of the Retinoic Acid Systemmentioning

confidence: 99%

A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals

Helfer

Barrett

Morgan

2019

J Neuroendocrinology

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“…Previous studies have shown the importance of local synthesis of both TH and RA within the HVZ of the hypothalamus to the photoperiodic response24 and recent work has revealed that TH regulates the expression of Raldh1 suggesting that TH drives the photoperiodic response at least in part through RA signalling9 (Fig. 7).…”

Section: Discussionmentioning

confidence: 91%

“…Ex-vivo hypothalamic slice cultures were set up as previously described9. Slices were treated for 48 hrs with 1 μM RA or an equivalent concentration of DMSO (0.1%) diluted in culture medium.…”

Section: Methodsmentioning

confidence: 99%

“…TSH controls expression of type 2 deiodinase and, depending on the species, type 3 deiodinase, which together regulate hypothalamic TH availability567. Hypothalamic RA synthesis and signalling is also under strong photoperiodic regulation within the HVZ8 and is directly regulated by TH9. It is now generally accepted that changes in hypothalamic TH levels and downstream RA signalling within the neuroendocrine system lead to seasonal changes in body weight, food intake and reproduction24.…”

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A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance

Helfer

Ross

Thomson

et al. 2016

Sci Rep

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Long-term and reversible changes in body weight are typical of seasonal animals. Thyroid hormone (TH) and retinoic acid (RA) within the tanycytes and ependymal cells of the hypothalamus have been implicated in the photoperiodic response. We investigated signalling downstream of RA and how this links to the control of body weight and food intake in photoperiodic F344 rats. Chemerin, an inflammatory chemokine, with a known role in energy metabolism, was identified as a target of RA. Gene expression of chemerin (Rarres2) and its receptors were localised within the tanycytes and ependymal cells, with higher expression under long (LD) versus short (SD) photoperiod, pointing to a physiological role. The SD to LD transition (increased food intake) was mimicked by 2 weeks of ICV infusion of chemerin into rats. Chemerin also increased expression of the cytoskeletal protein vimentin, implicating hypothalamic remodelling in this response. By contrast, acute ICV bolus injection of chemerin on a 12 h:12 h photoperiod inhibited food intake and decreased body weight with associated changes in hypothalamic neuropeptides involved in growth and feeding after 24 hr. We describe the hypothalamic ventricular zone as a key site of neuroendocrine regulation, where the inflammatory signal, chemerin, links TH and RA signaling to hypothalamic remodeling.

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Tanycytes and hypothalamic control of energy metabolism

Ebling

Lewis

2018

Glia

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Studies from a number of areas of neuroendocrinology indicate that hypothalamic tanycytes play a key role in control of energy metabolism. First, profound annual changes in gene expression have been identified in these unusual glial cells in seasonal mammals, for example in genes relating to the transport and metabolism of thyroid hormone into the hypothalamus. The consequent changes in local thyroid hormone availability in the hypothalamus have been shown experimentally to regulate annual cycles in energy intake, storage and expenditure in seasonal species. This is reflected in overt seasonal changes in appetite, body fat composition and torpor. Second, studies in laboratory rodents demonstrate that hypothalamic tanycytes possess transport mechanisms and receptors that indicate they have a cellular function as nutrient sensors. Ex vivo studies with organotypic tanycyte cultures confirm that acute changes in nutrient availability alter calcium and purinergic signalling within and between tanycytes. Finally, tanycytes are components of a stem cell niche in the hypothalamus whose activity can be regulated by the nutritional environment. Experimental depletion of cell division in the hypothalamus alters the homeostatic response to nutrient excess in mice raised in high fat diets. These convergent lines of evidence suggest that tanycytes are nutrient and metabolite sensors that impact upon plasticity and neuronal function in the surrounding hypothalamus, and consequently have an important role in energy intake and expenditure.

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Thyroid hormone activation of retinoic acid synthesis in hypothalamic tanycytes

Cited by 24 publications

References 67 publications

A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals

A unifying hypothesis for control of body weight and reproduction in seasonally breeding mammals

A neuroendocrine role for chemerin in hypothalamic remodelling and photoperiodic control of energy balance

Tanycytes and hypothalamic control of energy metabolism

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