Control of cell growth. II. Requirement of thyroid hormones for the in vivo estrogen-dependent growth of rat pituitary tumor cells.
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-thyroixine 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.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002369:Castration; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000097:blood / Q000473:pathology; D010053:Ovary / Q000502:physiology; D010911:Pituitary Neoplasms / Q000097:blood / Q000473:pathology*; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D011920:Rats, Inbred WF; D013974:Thyroxine / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*
D004967:Estrogens; D008713:Methimazole; D011441:Propylthiouracil; D013974:Thyroxine