Effects of Triiodothyronine on Thyrotropin-Releasing Hormone-Induced Thyrotropin Release in the Neonatal Rat*

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Abstract
Control of pituitary TSH release in vivo and in vitro was studied in postnatal rats. Graded doses of TRH (10, 25, 50, or 100 ng/100 g BW) were injected sc to 5-, 11-, 14-, 22-, 25-, 32-, 40-, and 90 (adult)-day-old rats. The serum TSH concentration was measured by RIA 10 min later. TRH (100 ng/100 g BW) induced a 19-fold increase in the serum TSH concentration in 5-day-old rats. This increment decreased rapidly by 14 days of age. At 25 days of age, a further increase in the TSH response to TRH was noted. Adult level responses were attained by 32 days of age. To determine whether the observed changes in the 10 min serum TSH response to TRH reflected changes in the iodothyronine feedback control of TSH release, rats of the same developmental ages were injected with graded doses of T3 (0.1, 0.25, 0.5, and 1.0 μg/100 g BW) sc 4 h before the administration of 100 ng TRH/100 g BW. The dose of T3 which resulted in half-maximal inhibition of the 10 min serum TSH response to TRH was assessed as the amount of T3 injected per 100 g BW (D50). In addition, the increment in serum T3 (ΔD50) necessary to achieve half-maximal suppression of the TRH response was calculated. A progressive decline in the D50 was noted between 5 days (0.33 fμg T3/100 g BW) and 22 days of age (0.15 μg T3/100 g BW). The developmental change in the ability of T3 to suppress the TRH response was more apparent when the ΔD50 was examined. ΔD50 declined markedly from 78.2 ng/dl at 5 days to 44.3 ng/dl at 14 days. The ΔD50 increased transiently between 22 and 25 days. Adult level responses were observed at 40 days of age. Corroboration of the in vivo data was afforded in explant cultures of 5- and 22-day-old and adult rat pituitaries. Pituitaries from 5-day-old rats released significantly more TSH than those of adult animals when exposed to similar TRH concentrations in the presence of T3 (10-9 M). In vitro pituitary TSH release in 22-day-old rats was intermediate. These data indicate that dynamic changes in the maturation of control mechanisms for pituitary TSH release occur during postnatal life in the rat.