Phorbol esters stimulate growth and inhibit differentiation in cultured thyroid cells.
Phorbol esters stimulate growth and inhibit differentiation in cultured thyroid cells.
复制标题
佛波酯刺激培养的甲状腺细胞的生长并抑制分化。
作者：
L. Bachrach;M. Eggo;W. Mak;G. Burrow
有效的肿瘤促进剂12-O-十四酰基佛波醇13-乙酸酯（TPA）对细胞生长和分化具有生物学作用，类似于表皮生长因子（EGF）对多种细胞的作用。由于表皮生长因子已被证明最近刺激甲状腺细胞增殖和抑制碘代谢，我们研究了佛波醇酯对原代绵羊甲状腺文化的影响。TPA以类似于EGF的方式刺激细胞生长。EGF和TPA的组合的生长效果不是加和的。相比之下，TPA（1.6 × 10（-7）M）在其最大有效浓度下是比EGF（10（-9）M）更有效的碘摄取和掺入抑制剂。TPA的抑制作用也比EGF更快，更不可逆。TPA和EGF组合抑制碘代谢比单独使用任何一种药物在其最大有效浓度。TPA和EGF均能抑制TSH刺激的细胞内cAMP的积累，但（Bu）2cAMP和腺苷酸环化酶刺激剂不能克服TPA对碘代谢的抑制作用。TPA通过降低膜受体对[125 I]碘-EGF的亲和力与EGF相互作用。虽然TPA诱导的EGF-受体相互作用的改变可能在介导TPA的生物学效应中发挥作用，但TPA和EGF对碘代谢的累加效应表明TPA并不完全通过EGF受体效应系统起作用。促甲状腺激素以外的药物，包括佛波醇酯和表皮生长因子，是甲状腺生长和分化功能的有效调节剂。尽管TPA和EGF在生物活性上有一些相似之处，但它们并不以相同的方式调节分化的功能。这两种因子至少部分通过非cAMP依赖性途径起作用，提供了另一种第二信使控制甲状腺功能的间接证据。
The potent tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) has biological effects on cell growth and differentiation similar to the effects of epidermal growth factor (EGF) on a variety of cells. Since EGF has been shown recently to stimulate thyroid cell proliferation and inhibit iodine metabolism, we examined the effects of phorbol esters on primary ovine thyroid cultures. TPA stimulated cell growth in a manner similar to EGF. The growth effects of EGF and TPA in combination were not additive. In contrast, TPA (1.6 X 10(-7) M) was a more potent inhibitor of iodine uptake and incorporation than EGF (10(-9) M) at their maximally effective concentrations. The inhibitory effects of TPA were also more rapid and less reversible than those of EGF. TPA and EGF in combination inhibited iodine metabolism more than either agent alone at its maximally effective concentration. Both TPA and EGF reduced the accumulation of cAMP in TSH-stimulated cells, but (Bu)2cAMP and stimulators of adenylate cyclase failed to overcome TPA's inhibition of iodine metabolism. TPA interacted with EGF by reducing the affinity of membrane receptors for [125I]iodo-EGF. Although the alteration in EGF-receptor interaction induced by TPA may play a role in mediating TPA's biological effects, the additive effects of TPA and EGF on iodine metabolism suggest that TPA does not act solely through the EGF receptor-effector system. Agents other than TSH, including phorbol esters and EGF, are potent modulators of thyroid growth and differentiated function. Despite several similarities in biological activity, TPA and EGF do not modulate differentiated function in an identical manner. Both factors act at least partially through a non-cAMP-dependent pathway, providing indirect evidence of another second messenger(s) in the control of thyroid function.
DOI：
10.1073/pnas.80.1.36
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
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作者：
NIEDEL, JE;KUHN, LJ;VANDENBARK, GR
通讯作者：
VANDENBARK, GR