Tanycyte Pyroglutamyl Peptidase II Contributes to Regulation of the Hypothalamic-Pituitary-Thyroid Axis through Glial-Axonal Associations in the Median Eminence (original) (raw)

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1Tupper Research Institute and Department of Medicine (E.S., P.S.S., C.F., R.M.L.), Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, Boston, Massachusetts 02111

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2Departamento de Genética del Desarrollo y Fisiología Molecular (M.A.V., F.R., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62271, México; Universidad de la Habana, La Habana, 10400, Cuba

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1Tupper Research Institute and Department of Medicine (E.S., P.S.S., C.F., R.M.L.), Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, Boston, Massachusetts 02111

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3Department of Centro de estudios de proteínas (I.P.), Facultad de Biología, Universidad de la Habana, La Habana, 10400, Cuba

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2Departamento de Genética del Desarrollo y Fisiología Molecular (M.A.V., F.R., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62271, México; Universidad de la Habana, La Habana, 10400, Cuba

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1Tupper Research Institute and Department of Medicine (E.S., P.S.S., C.F., R.M.L.), Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, Boston, Massachusetts 02111

4Department of Endocrine Neurobiology (C.F.), Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1083, Hungary

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2Departamento de Genética del Desarrollo y Fisiología Molecular (M.A.V., F.R., J.-L.C.), Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor. 62271, México; Universidad de la Habana, La Habana, 10400, Cuba

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1Tupper Research Institute and Department of Medicine (E.S., P.S.S., C.F., R.M.L.), Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, Boston, Massachusetts 02111

5Department of Neuroscience (R.M.L.), Tufts University School of Medicine, Boston, Massachusetts 02111

*Address all correspondence and requests for reprints to: Ronald M. Lechan M.D., Ph.D., Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center, Box No. 268, 750 Washington Street, Boston, Massachusetts 02111.

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Received:

21 November 2008

Accepted:

16 January 2009

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Edith Sánchez, Miguel Angel Vargas, Praful S. Singru, Isel Pascual, Fidelia Romero, Csaba Fekete, Jean-Louis Charli, Ronald M. Lechan, Tanycyte Pyroglutamyl Peptidase II Contributes to Regulation of the Hypothalamic-Pituitary-Thyroid Axis through Glial-Axonal Associations in the Median Eminence, Endocrinology, Volume 150, Issue 5, 1 May 2009, Pages 2283–2291, https://doi.org/10.1210/en.2008-1643
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Pyroglutamyl peptidase II (PPII), a highly specific membrane-bound metallopeptidase that inactivates TRH in the extracellular space, is tightly regulated by thyroid hormone in cells of the anterior pituitary. Whether PPII has any role in the region where axons containing hypophysiotropic TRH terminate, the median eminence, is unknown. For this purpose, we analyzed the cellular localization and regulation of PPII mRNA in the mediobasal hypothalamus in adult, male rats. PPII mRNA was localized in cells lining the floor and infralateral walls of the third ventricle and coexpressed with vimentin, establishing these cells as tanycytes. PPII mRNA extended in a linear fashion from the tanycyte cell bodies in the base of the third ventricle to its cytoplasmic and end-feet processes in the external zone of the median eminence in close apposition to pro-TRH-containing axon terminals. Compared with vehicle-treated, euthyroid controls, animals made thyrotoxic by the ip administration of 10 μg l-T4 daily for 1–3 d, showed dramatically increased accumulation of silver grains in the mediobasal hypothalamus and an approximately 80% increase in enzymatic activity. PPII inhibition in mediobasal hypothalamic explants increased TRH secretion, whereas ip injection of a specific PPII inhibitor increased cold stress- and TRH-induced TSH levels in plasma. We propose that an increase in circulating thyroid hormone up-regulates PPII activity in tanycytes and enhances degradation of extracellular TRH in the median eminence through glial-axonal associations, contributing to the feedback regulation of thyroid hormone on anterior pituitary TSH secretion.

Copyright © 2009 by The Endocrine Society

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