IN-VIVO RESPONSIVENESS OF THYROID-GLANDS TO TSH IN NORMAL AND NOVEL GROWTH-RETARDED MICE - TRANSIENT ELEVATION IN NORMAL MICE AND IMPAIRMENT IN GROWTH-RETARDED MICE

The in vivo responsiveness of thyroid glands to TSH at various ages in novel 'growth-retarded' (grt/grt) mice derived from Snell's dwarf (DW/J) mice and in their normal counterparts were analysed by determining serum T-4 concentrations before and after the administration of exogenous TSH. The serum T-4 concentration in normal mice increased in response to TSH at 2, 4 and 12 weeks of age but not at 1 week of age. A transient augmentation of such thyroidal responsiveness to TSH was apparent in normal mice at 2 weeks of age, when the serum T-4 level exhibits a peak and the pubertal growth of mice starts. In contrast to normal mice, at any age examined from 2 to 12 weeks after birth, exogenous TSH did not influence serum T-4 concentrations in the grt/grt mice at all. On the other hand, serum TSH concentrations in young grt/grt mice were highly elevated compared with those in normal mice and they were normalized by a 2-3 week's treatment with T-3. Morphological studies demonstrated degenerated thyroid glands in the grt/grt mice. These results suggest that the severe hypothyroidism and consequent growth retardation in growth-retarded mice are due to impairment of the thyroid glands of the mutant mice in producing and/or secreting thyroid hormones in response to TSH.