ABSTRACT
The campaign for passage and implementation of Pittsburgh's Smoking Control Ordinance in 1987 illustrates the role controversy plays in tobacco control. Proponents of the ordinance sought at first to keep it noncontroversial, while the tobacco industry tried to defeat the ordinance by generating controversy, claiming that severe economic and social disruption would occur. After the ordinance had been in force for a year, Philip Morris tried to take over its implementation, seeking to redefine the central issue as one of social accommodation rather than health. To succeed, Philip Morris's effort had to be widely accepted and noncontroversial. Proponents of the ordinance countered with controversy to undermine the campaign and expose the company's intentions. The controversy made the established health organizations uncomfortable, causing them to play only a marginal role. Surprisingly, the people who prevailed were the nonsmokers' rights activists, a small group with limited resources.
Subject(s)
Industry , Politics , Smoking/legislation & jurisprudence , Health Care Coalitions , Humans , Mass Media , Pennsylvania , Public OpinionABSTRACT
The nuclear receptor affinity for L-triiodothyronine (L-T3), L-thyroxine (L-T4), L-triiodothyroacetic acid (triac), and D-triiodothyronine (D-T3) was compared to the potency of these thyroid hormone analogues in regulating thyrotropin (TSH) production and the number of membrane receptors for thyrotropin-releasing hormone (TRH) in mouse thyrotropic tumor cells in culture. L-T3 and triac were equally potent and D-T3 was one-sixth to one-fifth as potent in binding to the receptor and in regulating TSH production and TRH receptor number. L-T4 was the least potent analogue in each instance, but its relative receptor-binding affinity, measured after 3 h, was significantly less than its somewhat variable relative biological potency, measured after 48 h. The cells were shown to monodeiodinate L-[125I]T4 to L-[125I]T3 in a time-dependent manner, and the enhanced biological potency of L-T4 was ascribed to its conversion to L-T3. Thyroid hormones appear to regulate TSH production and the number of receptors for TRH in thyrotropic cells in culture through interaction with a nuclear receptor.
Subject(s)
Receptors, Cell Surface/metabolism , Thyroid Hormones/metabolism , Thyrotropin-Releasing Hormone , Thyrotropin/biosynthesis , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Mice , Structure-Activity Relationship , Thyroxine/analogs & derivatives , Thyroxine/pharmacology , Triiodothyronine/analogs & derivatives , Triiodothyronine/pharmacologyABSTRACT
The number of plasma membrane receptors for TRH on tumor-derived mammotropic cells in culture, GH3 and GC cells, but not their affinity for TRH, was increased by estrogens. For GH3 cells, exposure to 10 nM 17 beta-estradiol for 48 h increased the receptor level from 54,000 to 90,000 sites/cell, while for GC cells, the number of receptors increased from 29,000 to 46,000 after 28 h. PRL accumulation in the medium was also increased by 17 beta-estradiol. 17 beta-Estradiol and diethylstilbestrol were equally potent in increasing the TRH receptor level, while estrone was only 1/10th as potent. Diethylstilbestrol bound to the cytoplasmic estrogen receptor with an apparent affinity approximately 2.5 times higher than 17 beta-estradiol in GH3 and GC cells, while the affinity for estrone was only 1/12th to 1/20th that of 17 beta-estradiol. Tamoxifen, an antiestrogenic compound, inhibited the increase in TRH receptor number induced by 0.3 nM 17 beta-estradiol and was capable of binding to the estrogen receptor. Modulation of the TRH receptor level on mammotropic cells by estrogens, which is likely mediated through cytoplasmic estrogen receptors, may be an important mechanism for regulation of TRH action.
