EXPRESSION OF CORTICOTROPIN-RELEASING FACTOR AND ITS RECEPTORS IN THEBRAIN OF LEAN AND OBESE ZUCKER RATS

Expression of CRF messenger RNA (mRNA) and heteronuclear RNA (hnRNA) a s well as the mRNAs encoding the CRF receptors of type 1 (CRF(1)R) and type 29 (CRF(2)R) in the brain has been investigated in lean (Fa/?) a nd obese (fa/fa) Zucker rats. Exonic and intronic in situ hybridizatio n histochemistry was employed to measure the mRNA and hnRNA levels in rats killed before (resting state), during, and 120 min after a treadm ill running session. The resting expression of CRF hnRNA in the hypoth alamic paraventricular nucleus (PVN) of obese rats was minimal and com parable to that of lean rats. However, during treadmill running, this expression was higher in obese than in lean rats. In obese rats, the t ranscription of the CRF(1)R mRNA in the PVN was high under resting con ditions, dropped considerably during running, and rose again to elevat ed levels 120 min after the treadmill session. In lean rats, CRF(1)R m RNA in the PVN was minimal before and during running, but rose to a va lue similar to that in obese rats 120 min after running. In the PVN of obese rats, expression of the CRF(1)R gene measured during resting co nditions was comparable to the level seen after running and proved to be dependent upon the feeding state of the rats. Expression of the CRF (2)R transcript was reduced in the ventromedial nucleus of the hypotha lamus (VMH) of the obese rat. Plasma ACTH concentrations during treadm ill running were lower in obese than in lean animals. Basal and postru nning levels of circulating corticosterone were higher in fa/fa than i n Fa/? rats. However, there was no difference in corticosterone levels between lean and obese animals during running. The present results pr ovide evidence for differences between lean and obese rats in the expr ession of CRF and its receptor within selective hypothalamic nuclei. G iven the anorectic and thermogenic properties of CRF and the roles of PVN and VMH in the regulation of energy balance, it can be argued that the observed alterations in the biosynthesis of CRF and its receptors within the PVN and VMH might be related to the development of obesity .