Estrogen induction of growth hormone in the thyroidectomized rat.
GH production in the rat is almost completely dependent upon T3. Estrogens also stimulate GH in some rat models, and androgens have well documented stimulatory effects. This study examined estrogen and androgen effects on pituitary GH in rats with differing thyroid status. Diethylstilbesterol (DES; a potent synthetic estrogen, 5 mg Silastic implant), estradiol benzoate (50 micrograms/kg.48 h), or testosterone propionate (10 mg/kg.48 h) were administered for 3 weeks to ovariectomized rats that were either thyroid-intact or thyroid-ectomized. In intact rats, DES produced a 40% decrease in pituitary GH, whereas estradiol (at a lower relative dose) had no effect; testosterone produced a 65% increase in pituitary GH. Thyroidectomy decreased pituitary GH to less than 0.5% of intact values. DES and estradiol produced 50- to 70-fold increases in pituitary GH in thyroidectomized rats--reaching 23-36% of intact levels. In contrast, testosterone had no effect in thyroidectomized rats. Tamoxifen (an antiestrogen; 1 mg/kg.24 h) increased GH by 15-fold in thyroidectomized rats and completely blocked further GH induction by estradiol. T3 (20 micrograms/kg.24 h) increased pituitary GH levels by 200-fold in thyroidectomized rats--totally reversing the decrease produced by thyroidectomy; tamoxifen inhibited GH induction by T3 by 63%. The results indicate that estrogens powerfully induce pituitary GH in thyroidectomized but not intact rats through an estrogen receptor-mediated process. The DNA-binding domains of estrogen and T3 receptors, as well as their hormone response elements, share structural similarities. The present results are consistent with the hypothesis that estrogens and estrogen receptors may induce GH through unoccupied T3 response elements of the GH gene in thyroidectomized rats.
Department of Pharmacology, New York Medical College, Valhalla 10595.
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D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D013006:Growth Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013629:Tamoxifen / Q000494:pharmacology; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000494:pharmacology
D004965:Estrogen Antagonists; D004967:Estrogens; D014284:Triiodothyronine; D013629:Tamoxifen; D004958:Estradiol; D004054:Diethylstilbestrol; D013006:Growth Hormone