Central regulation of thyrotropin secretion in rats: methodological aspects, problems and some progress

The concept of the regulatory role of the hypothalamic and brain neurotransmitters in the secretion of the hypothalamic releasing hormones and corresponding anterior pituitary hormones has been generally accepted. The tuberoinfundibular portal vessels form an anatomical framework for regulating these hormones. Our present knowledge about the origin and course of the main aminergic and peptidergic bundles and their collaterals into the hypothalamus conforms with the accepted concept. The general methods in neuroendocrinology are well established. In our study, the unique TSH burst induced by a short cold-exposure has proved very useful, since it is mediated through the activation of TRH in the hypothalamus. When used together with the TSH-response caused by the exogenous TRH and with stereotaxic microinfusions of various chemicals into specific areas in the brain, the level of action of the pharmacological agents can be determined. Methodological pitfalls are, however, possible unless care is taken to avoid unspecific stress factors, general anaesthesia and intracerebral injections at unphysiological concentrations. The role of different neurotransmitters in the central TRH-TSH regulation has been clarified in recent years and the simple concepts of the early days elaborated accordingly. The cold-stimulated TSH secretion can be modified by several neurotransmitters. Noradrenaline is a stimulatory transmitter at high hypothalamic centers, but it may also retard TRH release into the portal vessels. It also seems possible that alpha 1- and alpha 2-receptors mediate opposite effects. Nigrostriatal (but not tuberoinfundibular) dopamine has only an inhibitory action on TRH release and/or synthesis. The importance of 5-HT is still controversial, partly because of the unspecificity of the experimental tools available. Evidently both stimulating and inhibiting components are involved. The role of different 5-HT receptors remains to be established. The function of GABA is complicated, too, the real GABAergic action being an inhibition of TRH release from the medial basal hypothalamus. Only histamine and some amino acids affect TRH-induced TSH secretion. Hence the anterior pituitary in the rat is not so important a locus as the hypothalamus in the action of neurotransmitters on the TRH-TSH regulation.