Regulation of TRH neurons and energy homeostasis-related signals under stress

Abstract

Energy homeostasis relies on a concerted response of the nervous and endocrine systems to signals evoked by intake, storage, and expenditure of fuels. Glucocorticoids (GCs) and thyroid hormones are involved in meeting immediate energy demands, thus placing the hypothalamo-pituitary-thyroid (HPT) and hypothalamo-pituitary-adrenal axes at a central interface. This review describes the mode of regulation of hypophysiotropic TRHergic neurons and the evidence supporting the concept that they act as metabolic integrators. Emphasis has been be placed on i) the effects of GCs on the modulation of transcription of Trh in vivo and in vitro, ii) the physiological and molecular mechanisms by which acute or chronic situations of stress and energy demands affect the activity of TRHergic neurons and the HPT axis, and iii) the less explored role of non-hypophysiotropic hypothalamic TRH neurons. The partial evidence gathered so far is indicative of a contrasting involvement of distinct TRH cell types, manifested through variability in cellular phenotype and physiology, including rapid responses to energy demands for thermogenesis or physical activity and nutritional status that may be modified according to stress history.

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

“…Depending on the origin of stress (physical or psychogenic), its duration and the animal’s endocrine and energetic status TRH release may be upregulated or downregulated (157) subsequently affecting the set point of the overall homeostatic system. Downregulation with consecutive thyrotropic adaptation, i.e., low or normal TSH levels despite low concentrations of T4 and/or T3, may occur for instance in cases of systemic infection and sepsis, where lipopolysaccharides induce D2 activity in tanycytes (126).…”

New insights into thyroid hormone action

“…Taken together these data suggest that while NCoR1 and HDAC3 are necessary for the repressive effects of the TR, the exact molecular mechanism remains unclear. This is further complicated by the fact that the TR has the ability to activate certain targets such as TRH in the hypothalamus or FBXO21 in the liver in the hypothyroid state (Joseph-Bravo, Jaimes-Hoy, & Charli, 2015) (Astapova et al, 2008). The role of coregulators in so-called ligand-independent activation is not understood at all.…”

Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment

“…Hypothalamic tancytes strongly express the relatively more T3- than T4-affine thyroid hormone transporter MCT8 and deiodinase type 2 and 3, enabling them to sense FT3 and FT4 levels ( 41 , 44 – 46 ). They also respond to alterations in the energetic and metabolic needs of the body and interact with TRH neurons ( 41 , 42 , 44 – 48 ). Fat cells release adipokines such as leptin into the circulation which directly or indirectly stimulate pituitary TSH secretion ( 36 , 39 , 40 , 42 , 45 ).…”