Control of cell growth. II. Requirement of thyroid hormones for the in vivo estrogen-dependent growth of rat pituitary tumor cells

• Published in: JNCI : Journal of the National Cancer Institute 1976-06, Vol.56 (6), p.1155-1158
• Main Authors: Sorrentino, J M, Kirkland, W L, Sirbasku, D A
• Format: Article
• Language: English
• Subjects: Animals; Body Weight - drug effects; Castration; Cell Division - drug effects; Cell Line; Estrogens - pharmacology; Female; Male; Methimazole - pharmacology; Neoplasms, Experimental - blood; Neoplasms, Experimental - pathology; Ovary - physiology; Pituitary Neoplasms - blood; Pituitary Neoplasms - pathology; Propylthiouracil - pharmacology; Rats; Rats, Inbred WF; Thyroxine - biosynthesis; Thyroxine - blood; Thyroxine - physiology
• ISSN: 0027-8874

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.