Activation of estrogen response element dependent transcription by thyroid hormone with increase in estrogen receptor levels in a rat pituitary cell line, GH3.

Interrelationships between thyroid hormone and estrogen actions have been documented with regard to a variety of physiological functions. Both hormones stimulate transcription of target genes by binding to their nuclear receptors that interact with specific responsive elements (estrogen and thyroid hormone response elements, i.e ERE and TRE, respectively) in the regulatory regions of the gene. In vitro studies have suggested that interplay between the two hormones might be due to cross-talk at hormone responsive elements, with the respective hormone receptors and ligands able to interact, although physiological relevance has yet to be proved. We have proposed a simpler mechanism for thyroid hormone effects on estrogen responses via increase in estrogen receptor alpha (ERalpha) with resultant increase in progesterone receptors, prolactin production and tumor growth. A pituitary cell line, GH3, has been widely used to investigate the function of mammo-somatotropic cells, especially regarding regulation of GH and prolactin production. In the present study, an ERE-luc reporter was transfected into GH3 cells and the responses to endogenous ERalpha were examined. We demonstrated that: (1)l -3,5,3'-triiodothyronine (T3) induces mRNA expression of ERalpha; (2) T3 alone is able to induce ERE-luc activity and this is inhibited by OH-tamoxifen; (3) T3 synergistically acts on estradiol (E2)-induced ERE responses; and (4) ERE-luc activity is enchanted by co-transfection of an ERalpha expression vector. These results support the hypothesis that estrogen responses are potentiated by T3 through up-regulation of ERalpha levels.

Whole-body metabolism of the organophosphorus pesticide, fenthion, in goldfish, Carassius auratus.

The in vivo metabolism of fenthion, an organophosphorus pesticide, and its sulfoxide (fenthion sulfoxide) was examined in goldfish (Carassius auratus). When goldfish were administered fenthion i.p. at a dose of 100 mg/kg, two metabolites were isolated from the tank water. They were identified as fenthion sulfoxide and fenthion oxon, in which > P = S of fenthion is transformed to > P = O, by comparing their mass and UV spectra, and their behavior in HPLC and TLC, with those of authentic standards. However, fenthion sulfone was not detected as a metabolite. The amounts of fenthion, fenthion sulfoxide and fenthion oxon excreted within 4 days were 2.7, 3.4 and 2.5%, of the initial dose of fenthion, respectively. Unchanged fenthion was detected in the body of the fish to the extent of 42-50% of the dose after 10 days, but fenthion sulfoxide and fenthion oxon showed very low concentrations. When fenthion sulfoxide was administered to the fish, about 70% of the dose was excreted unchanged into the tank water within 24 h, but little of the reduced compound, fenthion, was found. In contrast, fenthion was detected at 2.1% of dose in the body of goldfish as a metabolite of fenthion sulfoxide. The fact that fenthion is metabolized to the toxic oxon form in fish presumably has environmental and health implication for its use as a pesticide.