The Role of Adenosine 3′,5′-Monophosphate in the Regulation of Receptors for Thyrotropin and Insulin-Like Growth Factor I in the FRTL5 Rat Thyroid Follicular Cell*

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Abstract
Although regulatory effects on their own receptors are among the major responses to peptide hormones and growth factors, little is known of the mechanism of these effects. For example, a wealth of evidence indicates that cAMP is the mediator of many, if not most, of the actions of TSH on the growth and function of the thyroid cell, but evidently no information has been available concerning the possibility that cAMP may also mediate the effect of TSH to down-regulate its own receptors. Therefore, we examined this question using FRTL5 cells as a model, since we had previously shown that withdrawal of TSH from their culture medium and its subsequent readdition lead to increases and decreases, respectively, in the number of their TSH receptors. Because the growth of FRTL5 cells in response to TSH is modified by insulin-like growth factor I (IGF-I), we also examined the independent effect of TSH on receptors for IGF-I, the effects of IGF-I alone on both its own receptors and those for TSH, the effects of the two agents when added together, and the role of cAMP in the independent and conjoint effects of TSH and IGF-I on their own and each other''s receptors. Growth of FRTL5 cells in the presence of bovine TSH (bTSH) resulted in a dose-dependent down-regulation of receptors for both bTSH and IGF-I. In contrast, IGF-I alone produced only a modest down-regulation of its own receptors and had no effect on the binding of bTSH. IGF-I did, however, enhance the effect of bTSH on the binding of both ligands. All of the foregoing down-regulatory effects of bTSH, acting both alone and together with IGF-I, were closely mimicked when either (Bu)2cAMP or forskolin was substituted for bTSH. Therefore, cAMP appears to mediate, at least in part, the effects of both bTSH alone and bTSH acting in concert with IGF-I to down-regulate receptors for both mitogens.

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