Treatment of rats with thyrotropin (TSH) reduces the adrenoceptor sensitivity of adenylate cyclase from cerebral cortex.
Prolonged treatment of rats with TSH attenuates the noradrenaline (NA) sensitivity of the cerebral cortical cAMP generating system. This effect can be measured in slices from brain cortex and with a membraneous, cellfree adenylate cyclase preparation from the same brain region. The development of this downregulation is time (7 d treatment required) and dose dependent (EC(50) = 3.5 mU/kg for 9 d). After discontinuation of treatment, about 12 d were required for reversal of this effect. Density of ?-adrenoceptors in cerebral cortex as measured by (?) [ (3)H]dihydroalprenolol (DHA) binding was reduced by TSH treatment (22% reduction). The catalytic activity of adenylate cyclase as tested with guanosinemonophosphate phosphoimidophosphate (GMPPNP) was unaffected by TSH treatment. It is suggested that TSH-mediated feedback mechanisms on TRH levels and receptors in brain are responsible for the changes of the central adrenoceptor system. The data are discussed with respect to the blunted TSH-response to TRH observed in certain psychiatric illnesses.
Schultz
J E
JE
Pharmazeutisches Institut, Universität Tübingen, Morgenstelle 8, 7400 Tübingen, F.R.G.
Schmidt
B H
BH