ANALYSIS OF NUCLEAR 3,5,3'-TRIIODOTHYRONINE-BINDING CAPACITY AND TISSUE-RESPONSE IN THE LIVER OF THE NEONATAL RAT

Studies were undertaken to determine the hepatic response to T3 administration in the neonatal rat and to characterize the maximum T3-binding capacity in solubilized hepatic nuclei extracts. Scatchard analysis snowed that the equilibrium association constant gradually increased from 4.19 ± 0.58 × 109 M−1 (mean ± SEM) between birth and 5 days of age to a plateau value of 5.75 ± 1.02 × 109 M−1 between 21–30 days of age. Similarly, the maximum binding capacity was significantly greater in adult rats than in rats under 5 days of age (P <x 0.01). MBC reached a plateau between 21–30 days after birth. Thyroid hormone analog displacement studies were performed in 7-, 10-, and 24-day-old rats. Results indicate that T4, 3, 3′-diodothyronine, and rT3 bind to the receptor with the same affinity as in the adult animal. Measurement of the activity of the mitochondrial hepatic enzyme a-glycerophosphate dehydrogenase (α-GPD) showed that Ta (100 μg/100 g BW) induced a 2.0-fold increase in the activity of the enzyme 24 h after the administration of the hormone to neonatal rat. In addition, dose-response experiments indicate that there is a progressive increase in the dose of T3 necessary to obtain half-maximal effect (half-maximal effect, 0.9 μg/100 g BW at 3 days of age and 7.8 Mg/100 g BW for the adult). When hepatic nuclear T3 receptor sites of 10-day-old rats were continuously saturated by injecting 50.0 ng TV 100 g BW for a period of 1–5 days, the level of α-GPD response was 8-fold higher than in age-matched controls, suggesting a significant amplification of the hepatic α-GPD response to T3. Our results indicate that despite a 40-50% reduction in the number of neonatal hepatic T3 receptor sites, the response of α-GPD to T3 stimulation is not modified. On the other hand, major amplification of the hepatic α-GPD response to T3 is evident in the neonatal rat. Maturation of the hepatic nuclear T3 receptor is complete between 21–30 days of age. © 1979 by The Endocrine Society.