Hypothalamic Median Eminence Thyrotropin-Releasing Hormone-Degrading Ectoenzyme Activity Is Dispensable for Basal Thyroid Axis Activity in Lean Rodents

• DOI: 10.20944/preprints202502.1145.v1
• Publication Date: 2025-02-17T00:43:36Z
• Authors: Adair Rodríguez-R...; Rosa Maria Uribe; Antonieta Cote-Vélez; Patricia Joseph-B...; Jean-Louis Charli

The amplitude of the phasic output of thyrotropin-releasing hormone (TRH) into the hypothalamus-pituitary portal capillaries is likely controlled by the TRH-degrading ectoenzyme (TRH-DE) expressed on the surface of median eminence (ME) β2-tanycytes. To extend this hypothesis, we performed experiments in adult rodents reared in standard conditions. TRH-DE was close to the putative sites of TRH release in the male rat external layer of the ME. In global Trhde knock out mice, basal hypothalamus-pituitary-thyroid (HPT) axis parameters were not altered, but we detected an increased vimentin (a tanycyte marker) positive coverage of the portal vessels. We then overexpressed TRH-DE or a dominant negative isoform by microinjection of adeno-associated virus 1 (AAV1) vectors into the third ventricle of adult male rats. Two weeks after microinjection, cold stress-induced serum TSH concentration was decreased if ME TRH-DE activity had been enhanced. However, the long-term modification of TRH-DE activity in the ME had only a small impact on basal serum TSH concentration, but increased Trhr expression in the anterior pituitary of animals transduced with AAV1-TRH-DE. Thus, long-term modifications of ME TRH-DE activity lead to limited changes in serum TSH concentration in adult rodents reared in standard conditions, possibly because of adaptations of TRH communication in the ME and/or anterior pituitary.