Thyroid-thymus interaction on beta-adrenoceptor regulation during development and ageing.

Abstract

Up-regulation of brain cortex beta-adrenoceptors (beta ARs) can be induced by very acute stimulation with a single injection of T4 or T3 in young Balb/c-nu mice. We have also shown that this very rapid receptor increase can also be demonstrated in ageing animals when stimulated with T3 but not T4 injection. The aim of the present paper was to verify the capability of the thymus to reverse these impairments which we often observed in other experiments on old mice and young athymic nudes. The up-regulation induced by T4 and T3 was studied in normal and athymic nude young, normal old, and normal old and athymic nude young mice grafted with neonatal thymus 1 month earlier. In addition, since brain cortex bears both beta AR subpopulations, the eventual differential behavior of beta 1AR and beta 2AR subtypes was also investigated. Animals were injected intraperitoneally with saline, or saline containing 0.5 microgram T3 or 6.4 micrograms T4 per g body weight and killed 15 or 60 min after injection. Results show that thymus can recover the modifications of basal levels as well as T3-induced up-regulation of beta ARs in nude and old mice. On the contrary, impaired response to T4 stimulation is corrected in nude but not in old mice. The peripheral conversion of T4 into T3 can explain their differential influence since a correct conversion only occurs in presence of an efficient beta-adrenergic function. Thus, a vicious circle may occur with a decreasing number of beta-adrenoceptors causing in old age altered T4 to T3 conversion, in turn responsible for altered beta-adrenergic responsiveness to T4.