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

Abstract

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 i.p. administration of 10 microg L-T(4) 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 i.p. 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.

The saccus vasculosus of fish is a sensor of seasonal changes in day length

“…Coronet cells express vimentin and/or glial fibrillary acidic protein, markers of glial cells 28 . We observed expression of DIO2 in coronet cells, which seems reasonable because DIO2 is expressed in the vimentin-positive ependymal cells (also known as tanycytes) lining the ventrolateral walls of the third ventricle in birds and mammals 4,29 . In addition to photoreceptive and glial characteristics, coronet cells have been suggested to have endocrine function 15,27 .…”

60 YEARS OF NEUROENDOCRINOLOGY: TRH, the first hypophysiotropic releasing hormone isolated: control of the pituitary–thyroid axis

“…This response may be related to the rapid up-regulation of expression and activity of the TRHdegrading enzyme by T 4 in tanycytes. Increased inactivation of TRH released from the ME could account for diminished TSH release, supporting the external layer of the ME as an ultimate critical control point in modulating TRH concentration on its passage to the portal system (Sánchez et al 2009).…”

“…In the hypothalamus, PPII is expressed in neurons and in tanycytes whose cytoplasmic extensions reach the external layer of the ME, in proximity to TRH terminals (Joseph-Bravo et al 1998, Sánchez et al 2009). Cloning PPII (Schauder et al 1994) led to its identification as a member of the M1 family of metalopeptidases and, by homology modeling and sitedirected mutagenesis, interrogation of the structural determinants of its strict omega-peptidase specificity (Chávez-Gutiérrez et al 2006).…”

“…Cloning PPII (Schauder et al 1994) led to its identification as a member of the M1 family of metalopeptidases and, by homology modeling and sitedirected mutagenesis, interrogation of the structural determinants of its strict omega-peptidase specificity (Chávez-Gutiérrez et al 2006). Because PPII is an integral membrane protein with the active site exposed on the cell surface (Charli et al 1988), it is a prime candidate for TRH hydrolysis in the extracellular compartment, in particular before TRH reaches the ME-pituitary portal capillaries (Sánchez et al 2009). …”

Környezeti feltételváltozások és biológiai rendszerválaszok

“…Az infundibulum alatt található a pars tuberalis, itt módosult ependimasejteket (taniciták) találunk, amelyek a tobozmirigy és PRL termelő sejtek között teremtenek kapcsolatot (Sanchez et al 2009 Bergland et al, 1970). E porta-rendszernek lényeges szerepe van hipotalamusz és a hipofízis közötti kommunikáció kialakításában.…”