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An updated view of hypothalamic–vascular–pituitary unit function and plasticity

Key Points

  • The activity of hypothalamic neurons is modified by inputs leading to heterogeneous activity; a small proportion of the total population can drive pituitary hormone pulsatility

  • Neurohormone output can vary following neuron excitation according to the physiological status, which might also lead to declining neuroendocrine output with age

  • The release of hypothalamic factors into the blood is modified by alterations in the juxtaposition of nerve terminals with the vasculature and tanycytes in the median eminence

  • Cells in the pituitary gland form homotypic networks, and the organization and relationship of a network with the vasculature is distinct for each endocrine axis, which modifies responses to regulatory factors and patterns of output in response to demand

  • The reorganisation of the pituitary network can store long-term memories of increased output and enhance function on repeated challenge

  • Understanding the importance of coordinated hypothalamic–vasculature–pituitary function provides new understanding of a range of endocrine axes defects and targets for novel therapies

Abstract

The discoveries of novel functional adaptations of the hypothalamus and anterior pituitary gland for physiological regulation have transformed our understanding of their interaction. The activity of a small proportion of hypothalamic neurons can control complex hormonal signalling, which is disconnected from a simple stimulus and the subsequent hormone secretion relationship and is dependent on physiological status. The interrelationship of the terminals of hypothalamic neurons and pituitary cells with the vasculature has an important role in determining the pattern of neurohormone exposure. Cells in the pituitary gland form networks with distinct organizational motifs that are related to the duration and pattern of output, and modifications of these networks occur in different physiological states, can persist after cessation of demand and result in enhanced function. Consequently, the hypothalamus and pituitary can no longer be considered as having a simple stratified relationship: with the vasculature they form a tripartite system, which must function in concert for appropriate hypothalamic regulation of physiological processes, such as reproduction. An improved understanding of the mechanisms underlying these regulatory features has implications for current and future therapies that correct defects in hypothalamic–pituitary axes. In addition, recapitulating proper network organization will be an important challenge for regenerative stem cell treatment.

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Figure 1: A dynamic interplay between hypothalamic neuron output, the vasculature and the pituitary response alters hormone output.
Figure 2: Output of hypothalamic regulatory factors to the median eminence.
Figure 3: Pituitary cells form homotypic networks with distinct organizational motifs and relationships with the vasculature, which alter with the physiological status.
Figure 4: Updated view of the hypothalamic–vascular–pituitary unit.

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Acknowledgements

The authors thank F. Castinetti (Aix-Marseille Universite, France) for helpful comments and suggestions. P.L.T. was supported by a grant from the Biotechnology and Biological Sciences Research Council, UK, (BB/N007026/1). N.R. was supported by a Medical Research Council, UK, project grant (MR/J008893/1). D.J.H. was supported by an R.D. Lawrence Fellowship, Diabetes UK (12/0004431); European Foundation for the Study of Diabetes/Novo Nordisk Rising Star and Birmingham Fellowships; a Medical Research Council, UK project grant (MR/N00275X/1); Imperial Confidence in Concept, UK, and Wellcome Trust Institutional Support Awards, UK; and an European Research Council (ERC) Starting Grant (OptoBETA; 715884). P.M. was supported by funding from the Agence Nationale de la Recherche (ANR 12 BSV1 0032–01 and ANR-15-CE14-0012-01); INSERM; Centre National de la Recherche Scientifique; Université de Montpellier; Fondation pour la Recherche Médicale (DEQ20150331732); and IPAM-Biocampus of Montpellier and France-Bioimaging, all in France.

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Le Tissier, P., Campos, P., Lafont, C. et al. An updated view of hypothalamic–vascular–pituitary unit function and plasticity. Nat Rev Endocrinol 13, 257–267 (2017). https://doi.org/10.1038/nrendo.2016.193

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