Marked restoration of density and total number of mature (knob-bearing) olfactory receptor neurons in rats recovering from early hypothyroid-induced growth retardation.

Our recent studies have shown that restoration of thyroid function in developing hypothyroid rats results in upregulation of olfactory neurogenesis and compensatory proliferation of olfactory receptor neurons (ORN) in the olfactory epithelium (OE) (Paternostro and Meisami, Dev. Brain Res., 76 (1993) 151-161; ibid., 83 (1994) 151-162). It was not clear, however, whether the newly forming ORNs undergo complete maturational stages. To determine the effects of restoration of thyroid function on maturation of ORNs, the density and total number of mature ORNs were estimated in the OE of euthyroid and hypothyroid rats at postnatal days 1, 12, 25 and 90 and the results were compared with those in rats allowed to recover from early thyroid deficiency at weaning (day 25). As a marker for mature ORNs, and on the basis of one olfactory dendritic knob per ORN, the density and total number of the olfactory knobs were determined in the entire extent of the OE covering the nasal septum. Hypothyroidism was induced by adding propylthiouracil (PTU) to the drinking water (1 g/l) from birth until days 12, 25 or 90 of age. Recovery from hypothyroidism was induced by withdrawal of PTU at day 25, leading to restoration of thyroid function and somatic growth recovery. The density of olfactory knobs was determined in 1 microm semi-thin sections stained with toluidine blue. In the normal rats, the number of olfactory knobs (= mature ORNs) increased 8.5- and 3-fold during postnatal days 1-25 and 25-90 respectively, reaching a mean value of 4 X 10(6)/septal OE, compared to 2.8- and 1.4-fold, respectively, for the hypothyroid rats. This led to deficits of 51% and 76% in the number of mature ORNs in the 25- and 90-day-old hypothyroid rats. In rats allowed to recover, the number of mature ORNs increased 4.5-fold during postnatal days 25-90 (3 X > hypothyroid rats and 1.5 X > controls). The results indicate marked upregulation of the maturational process of the ORNs and their compensatory accretion within the OE of the recovery group. The recovery process was not complete however, as indicated by a remaining deficit of about 25% in the total number of mature ORN, compared to normal 90-day controls. Thus thyroid hormones are essential for accretion of new mature ORNs in both the suckling and postweaning rats. Also, the ORNs show a remarkable ability to recover from severe early hypothyroid-induced growth retardation and attain normal mature state.