COMPARATIVE EFFECTS OF THYROXINE AND OR RETINOIC ACID TREATMENT INVIVO ON GROWTH-HORMONE SYNTHESIS AND RELEASE BY PITUITARIES FROM THYROIDECTOMIZED RATS

Thyroid hormones and retinoic acid (RA) co-regulate growth hormone (GH) synthesis and release from cultured pituitary tumor cells by interacting with nuclear receptors that activate GH gene transcription. Whether these two compounds share overlapping GH regulatory activities in vivo is unclear. Therefore we compared the effects of in vivo replacement therapy with thyroxine (T4) and/or retinoic acid (RA) on GH synthesis and release in pituitaries from hypothyroid rats. Three weeks after thyroidectomy, male rats (100-150 grams, body weight) received 7 days of intraperitoneal T4 (20 ug/kg/day) and/or RA (500 ug/kg/day) or vehicle. Isolated pituitary fragments were incubated for 3h with [C-14]leucine followed by 2h with [H-3] leucine and 3 nM rat growth hormone-releasing hormone (GHRH). Basal synthesis. GHRH-induced release of stored [C-14]GH. and GHRH-stimulated release of newly synthesized [H-3]GH were assessed by specific immunopercipitation of media and tissue homogenates. T4 increased the synthesis of GH in the absence and presence of GHRH. T4, but not RA, increased the absolute amount of stored and newly synthesized GH released by GHRH. Neither T4 nor RA altered the percent of stored GH released by GHRH, however, both independently or additively decreased the percent of newly synthesized GH released by GHRH. In summary, treatment of hypothyroidism with T4 increased GH synthesis and absolute release. Interestingly the fractional release of GH was unchanged or decreased by T4 treatment. RA treatment had no effect on GH synthesis or absolute release, but like T4 it decreased the fractional release of newly synthesized GH. Thus T4 and RA did not share similar regulatory effects on GH synthesis and stored GH release but did have similar effects on the fractional release of newly synthesized GH in pituitaries from thyroidectomized male rats.