Hypothyroidism disrupts neural development in the olfactory epithelium of adult mice.

Adult mice made hypothyroid with propylthiouracil (PTU) lose their sense of smell. This is prevented by daily administration of thyroxine. As thyroxine is necessary for the correct development of the nervous system it may also be necessary for the genesis of new olfactory receptor neurones, a process that continues into adulthood. Adult mice were treated with PTU, injected with [3H]thymidine after 54 days and killed 5 or 15 days later. Microscopic analysis of the olfactory epithelium after autoradiography revealed similar numbers of labelled nuclei in the basal cell layer of the olfactory epithelia of Control and Hypothyroid mice 5 days after injection with [3H]thymidine. This indicated similar rates of basal cell division in the two groups. Fifteen days after [3H]thymidine injection, however, there were fewer labelled nuclei in the receptor cell layer of Hypothyroid mice and the olfactory epithelium was thinner than in Controls. Thyroxine therapy which reversed PTU-induced anosmia also reversed the epithelial effects of PTU treatment. Somewhat unexpectedly, there were no differences between the treatment groups in the average diameter of glomeruli in the olfactory bulb, and no differences in the expression of olfactory marker protein. The results indicate that although hypothyroidism disrupts neural development in the olfactory epithelium, it does not lead to a complete loss of mature receptor neurones.