Control of Cell Growth. II. Requirement of Thyroid Hormones for the In Vivo EstrogenDependent Growth of Rat Pituitary Tumor Cells2

Abstract

Further examination of rat pituitary cell line GH3/C14 showed that at least the physiologic concentration of l-thyroxine was required for estrogen-dependent growth in vivo. Two l-thyroxine synthesis inhibitors, 6-n-propyl-2-thiouracil (propylthiouracil) and 1-methylimidazole-2-thiol (methimazole), were administered concurrently with estrogen to GH3/C14-inoculated hosts. Propylthiouracil administration to estrogen-treated males, intact females, and estrogen-treated ovariectomized females inhibited tumor formation by 93, greater than 95, and 68%, respectively, as compared to tumor formation in controls not treated with propylthiouracil. Methimazole treatment of estrogen-primed males and intact females inhibited tumor formation by 78 and 95%, respectively. Concentrations of total l-thyroxine and free l>-thyroxine in sera from normal and inhibitor-treated hosts were depressed 70–80% by propylthiouracil and 60–70% by methimazole. Administration of either drug caused greater inhibition of tumor growth than of total body weight gain. In addition, the administration of a combination of l-thyroxine and l-triiodothyronine to male rats promoted tumor formation even in the absence of exogenous estrogen.