THYROTROPIN RELEASING HORMONE - ENDOCRINE AND CENTRAL EFFECTS
THYROTROPIN RELEASING HORMONE - ENDOCRINE AND CENTRAL EFFECTS
复制标题
DOI：
10.1016/0306-4530(85)90001-0
复制
发表时间：
1985-01-01
影响因子：
3.7
通讯作者：
GRIFFITHS, EC
中科院分区：
文献类型：
--
作者：
GRIFFITHS, EC
THYROTROPHIN-RELEASING hormone (TRH) was originally isolated and characterized from ovine and porcine hypothalamic tissue as the tripeptide, pyroglutamyl-histidylproline amide or pGlu-His-ProNH:(Jackson, 1982). Its functions as a hypothalamic regulatory hormone, stimulating the release of thyrotrophin (and perhaps other trophic hormones) from the anterior pituitary, adequately identify this tripeptide as a hormone. However, its widespread extrahypothalamic distribution and established functions which are independent of its endocrine activity in the hypothalamus-pituitary-thyroid axis suggest a much broader functional significance for TRH throughout the body. The endocrine and centrally-mediated behavioural effects of TRH are two facets of a spectrum of biological actions and have received some considerable attention (Jackson, 1982; Griffiths & Bennett, 1983; Yarbrough, 1983; Nemeroff et al., 1984). In the present review, some of the more recent findings concerning TRH, first of all as a hormone and secondly as a neurotransmitter or neuromodulator, will be considered, findings that are of importance in assessing the physiological significance of this tripeptide. These will include other hormonal activities not directly related to the thyroid, information on the biosynthesis of TRH, its release and receptor-mediated actions, the enzymes responsible for its inactivation and their role in the biotransformation to smaller, biologically-active fragments, and the localization of TRH in such diverse sites as the gastrointestinal tract, placenta and prostate gland. Finally, the pharmacological potential of TRH will be examined through the design and use of agonist and antagonist analogues, together with an assessment of the therapeutic value of such analogues. The possible clinical uses of TRH are certainly not limited to the endocrine properties of the tripeptide, and these deserve a wider appreciation.THE ENDOCRINE EFFECTS OF TRH The most obvious effect of T. RH, from which it derives its name, is the ability to stimulate the release of thyrotrophin (TSH) from the anterior pituitary through binding to high-affinity receptors and subsequent activation of adenyl cyclase (Jackson, 1982). Besides the negative-feedback effects of thyroid hormones, other factors such as noradrenaline, dopamine and somatostatin (both of hypothalamic origin) may well be involved in modifying TRH-stimulated TSH release (Jackson, 1982; Mannisto, 1983). Other neurotransmitters such as serotonin (5-HT), gamma-aminobutyric acid (GABA),
