title: PreproThyrotropin-releasing hormone 178-199 affects tyrosine hydroxylase biosynthesis in hypothalamic neurons: a possible role for pituitary prolactin regulation.
abstract: 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 preproTRH178-199 through its effect on DA neurons of the ARC. We observed that biotinylated preproTRH178-199 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 preproTRH178-199 peptide 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.
authors.affiliation: Division of Endocrinology, Department of Medicine, Brown Medical School, Rhode Island Hospital, Providence, RI 02903, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Goldstein
authors.forename: Mario
authors.initials: M
authors.lastname: Perello
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Nillni
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D030762:Estrous Cycle / Q000502:physiology; D005260:Female; D015686:Gene Products, env / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology* / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011247:Pregnancy; D011388:Prolactin / Q000097:blood / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis*
chemical_list: D015686:Gene Products, env; D010446:Peptide Fragments; D011498:Protein Precursors; C093834:peptide fragment P828; C063596:prepro-thyrotropin-releasing hormone; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine