TRH neurons of the parvocellular paraventricular nucleus (PVN) of the hypothalamus regulate adenohypophyseal secretions. Multiple neuronal inputs and various hormonal receptors (in particular for thyroid and glucocorticoid hormones) have been identified in PVN TRH neurons. The consequence of these inputs on TRH biosynthesis has recently been the subject of intense research. Hormones exert a negative feedback effect in vivo on TRH mRNA levels, presumably through transcriptional control. However, analysis of TRH mRNA regulation in primary cultures of fetal hypothalamic neurons has revealed that hormonal effects are highly dependent on the hormone dose and time of exposure suggesting multiple mechanisms of regulation. Stimuli which induce TRH release in vivo (cold stress or suckling) rapidly but transiently enhance TRH mRNA levels. Studies in primary cultures of hypothalamic neurons show that addition of camp analogs induces fast modifications of TRH mRNA levels that are dependent on glucocorticoid hormone concentration. Additional steps in TRH biosynthesis, in particular pro-TRH processing, are probably regulated. In vivo, regulation of TRH biosynthesis in response to cold stress or thyroid status preferentially occurs in specific regions of PVN. These observations demonstrate the existence of multiple pathways of regulation of TRH biosynthesis in PVN and suggest heterogeneity of the physiological properties of the PVN neurons.
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