Preprothyrotropin-releasing hormone178–199 affects tyrosine hydroxylase biosynthesis in hypothalamic neurons
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ProThyrotropin-releasing hormone (proTRH) is a prohormone widely distributed in many areas of the brain. After biosynthesis, proTRH is subjected to post-translational processing to generate TRH and seven non-TRH peptides. Among these non-TRH sequences, we found previously that preproTRH178–199 could regulate the secretion of prolactin in suckled rats by their pups. Dopamine (DA), the main regulator of prolactin secretion, is produced in dopaminergic tyrosine hydroxylase (TH)-positive neurons in the hypothalamic arcuate nucleus (ARC). In this study we investigated whether prolactin release during the estrous sexual cycle is regulated by prepro TRH178–199 through its effecton DA neurons of the ARC. We observed that biotinylated prepro TRH178–199 bound to neurons in the ARC; this was higher during proestrus than during diestrus. Binding of preproTRH178–199 to DA neurons was seen only during proestrus in the ARC. Using primary neuronal hypothalamic cultures we found that preproTRH178–199peptide decreased TH levels in a dose-responsive manner, whereas intra-ARC administration of preproTRH178–199 induced a 20-fold increase in plasma prolactin levels. Together, these results suggest a potential role for preproTRH178–199 in regulating dopaminergic neurons involved in the inhibition of pituitary prolactin release.
Index EntriesProTRH pepetides prolactin dopamine neurons arcuate nucleus
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