QUANTITATIVE [H-3] THYMIDINE AUTORADIOGRAPHY OF NEUROGENESIS IN THE OLFACTORY EPITHELIUM OF DEVELOPING NORMAL, HYPOTHYROID AND HYPOTHYROID-REHABILITATED RATS

We recently reported that postnatal hypothyroidism results in marked r eduction in surface area and cell number in the rat olfactory epitheli um (OE) and recovery from this condition is accompanied by compensator y growth and restitution of these parameters. To explore the correlati ve changes in olfactory neurogenesis, i.e. mitotic activity of basal c ells (BCs) and migration and survival of developing olfactory receptor neurons (ORNs), hypothyroid rats at postnatal (P) days of P10, P25 an d P75 were injected with [H-3]thymidine and OE was examined by quantit ative autoradiography to determine the density of labeled nuclei at th e BC and ORN zones at days 1, 5 and 15 post-injection. These data were compared with those of age-matched controls as well as young adult ra ts allowed to recover from hypothyroidism at the end of the suckling p eriod (P25). Hypothyroidism was induced by administration of propylthi ouracil (PTU) from birth in the drinking water (1 g/l) for 10, 25 and 90 days; recovery was induced by withdrawal of PTU at P25. The results indicated that the densities of labeled nuclei in the BC and ORN zone s were not significantly altered in the suckling hypothyroid rats. In the P75 hypothyroid rats density of labeled BC nuclei was unaffected 1 day after injection but was significantly (36%) more than controls 5 days after injection; the density of neuronal nuclei in the ORN zone o f P75 injected rats was markedly and significantly reduced (56% and 37 % at 5- and 15-days post-injection). Data indicate that mitotic activi ty of BCs and their migration into the ORN zone is not affected in the hypothyroid infant rats but migration and/or survival of developing O RNs are markedly reduced in the postweaning growing rats made hypothyr oid from birth. In rats allowed to recover from hypothyroidism at P25 and injected with labeled thymidine at P75, the density of labeled BC nuclei were significantly increased (48% and 43% at 1- and 5-days post -injection) compared to normal rats suggesting elevated levels of neur ogenesis; density of ORN nuclei, however, were the same as controls. T he results indicate critical regulatory influences of thyroid hormones on olfactory neurogenesis in the rat olfactory receptor sheet, in par ticular during the postweaning period.