Proliferation of thyrotropin releasing hormone receptors in specific brain regions during the development of hypertension in spontaneously hypertensive rats.
The binding of [3H] [3-MeHis2] thyrotropin releasing hormone [( 3H]MeTRH) to brain membranes prepared from 8 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats was determined. [3H]MeTRH bound specifically to rat brain membranes at a single high affinity site. The density (Bmax value) of [3H]MeTRH binding sites was significantly greater (28%) in SHR rats compared to WKY rats. The apparent dissociation constants (Kd values) for the binding of [3H]MeTRH in SHR and WKY rats did not differ. Binding in the various brain regions revealed that the density of [3H]MeTRH was highest in the hypothalamus followed in decreasing order by pons + medulla, midbrain, cortex and striatum. The binding of [3H]MeTRH was approximately 25% greater in cortex, hypothalamus and striatum of SHR rats in comparison to WKY rats. The binding in pons + medulla, midbrain and pituitary of SHR and WKY rats did not differ. To assess the significance of increased binding sites for [3H]MeTRH in some brain regions of SHR rats, the binding studies were carried out during normotensive and hypertensive stages of postnatal age in the two strains. In 3 and 4 week old SHR rats there was neither an increase in blood pressure nor any increase in [3H]MeTRH binding in the hypothalamus and striatum as compared to age matched WKY rats. With the development of elevated blood pressure at 6 weeks, an increase in [3H]MeTRH binding in the hypothalamus and striatum of SHR rats in comparison to the tissues from WKY rats was observed. The results provide, for the first time, evidence for a parallel increase in the density of brain TRH receptors with elevation of blood pressure, and suggest that brain TRH receptors may play an important role in the pathophysiology of hypertension.
D000375:Aging; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000503:physiopathology; D002462:Cell Membrane / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009928:Organ Specificity; D010902:Pituitary Gland / Q000254:growth & development / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR / Q000254:growth & development*; D011919:Rats, Inbred Strains / Q000254:growth & development*; D011921:Rats, Inbred WKY; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis* / Q000378:metabolism; D018025:Receptors, Thyrotropin-Releasing Hormone; D013045:Species Specificity; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone