Thyrotropin-releasing Hormone in the Pancreas and Brain of the Rat Is Regulated by Central Noradrenergic and Dopaminergic Pathways

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Abstract
These studies have been undertaken to evaluate the role of the brain noradrenergic and dopaminergic pathways in the regulation of the secretion of thyrotropin-releasing hormone (TRH) in the central nervous system (CNS) and pancreas of the neonatal rat. When CNS stores of norepinephrine (NE) were selectively reduced by the subcutaneous administration of the dopamine-β-hydroxylase inhibitor FLA-63, TRH concentrations were significantly reduced throughout the brain. However, when CNS stores of both NE and dopamine (DA) were depleted by the subcutaneous administration of the tyrosine hydroxylase inhibitor α-methyl-ρ-tyrosine (α-MT), TRH concentrations in the brain were not significantly altered. FLA-63 and α-MT did not significantly reduce pancreatic catecholamine concentrations, indicating that in the basal state, these agents predominantly deplete central catecholamine stores. Nevertheless, pancreatic TRH concentrations were markedly reduced by FLA-63, and this effect was significantly attenuated by the simultaneous intracerebroventricular (icv) administration of NE. In contrast to the effects of FLA-63, α-MT caused a significant increase in pancreatic TRH concentrations, and this effect was significantly lessened by icv DA. To determine whether the sympathetic nervous system might be one route by which these central effects are mediated, a chemical sympathectomy was induced with guanethidine. This treatment selectively reduced pancreatic concentrations of NE, and caused a marked increase in pancreatic TRH concentrations. From these observations, we conclude the following: (a) within the central nervous system, both NE and DA are involved in regulating brain TRH secretion or biosynthesis, and the direction of action of these two neurotransmitters appears to be opposite; (b) pancreatic TRH secretion or biosynthesis is also controlled by the brain noradrenergic and dopaminergic systems, and the net effects of each of these pathways appears to be opposite; (c) at least one route by which impulses from the brain may travel and modulate pancreatic TRH secretion or biosynthesis is by the sympathetic nervous system.