INTRAVENTRICULAR ADMINISTRATION OF THYROTROPIN-RELEASING-HORMONE (TRH) SUPPRESSES PROLACTIN SECRETION AND SYNTHESIS - A POSSIBLE INVOLVEMENT OF DOPAMINE RELEASE BY TRH FROM RAT HYPOTHALAMUS

The administration of thyrotrophin-releasing hormone (TRH) causes a variety of dopamine-related biological events. To understand the specific role of TRH on rat hypothalamic dopamine neurones, we examined the in-vivo effects of intraventricular (i.c.v.) infusion of TRH on the release and synthesis of prolactin in the rat pituitary gland and on the changes in binding of [H-3]MeTRH and dopamine turnover rates in rat hypothalamus. We have also examined the in-vitro effects of TRH on the release of [H-3]dopamine from dispersed tuberoinfundibular dopamine neurones. Female rats were treated with i.c.v. infusions of 1-mu-mol TRH/1 daily for 1, 3 and 7 days using Alzet osmotic pumps. Following 7 days of treatment the serum prolactin concentrations were significantly decreased. A reduction in hypothalamic TRH-binding sites (B(max)) was also apparent but the dissociation constant (K(d)) was unaffected. Northern blot analysis of total RNA isolated from the pituitary glands of control animals using P-32-labelled prolactin cDNA as a probe indicated the presence of three species of prolactin gene transcripts of approximately 3.7, 2.0 and 1.0 kb in size, and these were decreased by TRH treatment. We examined the turnover rate of dopamine in the rat hypothalamus when TRH was administered i.c.v. for 7 days. There was a significant increase in 3,4-dihydroxyphenylacetic acid/dopamine ratio with TRH treatment. Moreover, exposure to TRH stimulated [H-3]dopamine release from rat tuberoinfundibular neurones in a time- and dose-dependent manner. Dopamine receptor antagonists such as SCH23390 and (-)sulpiride, and other neuropeptides such as vasoactive intestinal peptide and oxytocin did not affect TRH-stimulated [H-3]dopamine release. These data suggest that i.c.v. administration of TRH might decrease both prolactin secretion and accumulation of prolactin gene transcripts in the pituitary by stimulating dopamine release from tuberoinfundibular neurones.