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

Abstract

AB S T R A C T 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-,B-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 a-methyl-p-tyrosine (a-MT), TRH concentrations in the brain were not significantly altered.FLA-63 and a-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, a-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.

Evidence of altered dopaminergic modulation of Prl, LH and TSH secretion in patients with normoprolactinaemic amenorrhoea

“…Pharmacological doses of MTC increase serum concentrations of TSH (Sowers et al 1976;Scanlon et al 1979;Massara et al 1983) probably due to a direct effect on the thyrotroph (Scanlon et al 1981;Foord et al 1980). In addition, in the rat dopamine inhibits TRH containing neurons directlv and stimulates the re¬ lease of hypothalamic somatostatin which in turn inhibits the release of TRH and thus of TSH (Engler et al 1982). The Prl response to MTC was decreased in the normoprolactinaemic amenor¬ rhoeic patients as recently reported by Quigley et al (1980).…”

Stress-Induced Inhibition of the Hypothalamic-Pituitary-Thyroid Axis Is Attenuated in the Aged Fischer 344/N Male Rat

“…Thus, stress-induced decrease in TRH might result in diminished corticotropin re lease inhibiting factor activity and potentially contribute to the rise of adrenocorticotropic hormone during stress. Immo induces increases in the PVN secretion of norepi nephrine [13], a physiological activator of hypothalamic TRH and CRH production [24]. However, because a decre ment rather than an increase in TRH mRNA levels is observed as a consequence of Immo in the present study, it is likely that during Immo the inhibitory influences of CRH and somatostatin are prevalent over the stimulatory in fluence of norepinephrine on the TRH neuron.…”

Expression of thyrotropin-releasing hormone receptor in immortalized beta-cell lines and rat pancreas

“…In addition to the hypothalamus, TRH has been identified in many systemic organs including the pancreas (Martino et al 1978, Koivusalco & Leppaluoto 1979, Morley et al 1979, Engler et al 1982, Aratan-Spire et al 1984, Leduque et al 1985, Fuse et al 1990). In the pancreas, TRH expression is at its peak during the neonatal period and gradually declines after birth (Martino et al 1978, Basmaciogullari et al 2000.…”