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Kaneko M, Okada R, Yamamoto K, Nakamura M, Mosconi G, Polzonetti-Magni AM, Kikuyama S: Bisphenol A acts differently from and independently of thyroid hormone in suppressing thyrotropin release from the bullfrog pituitary. Gen Comp Endocrinol. 2008 Feb 1;155(3):574-80. Epub 2007 Sep 19. The objective of this investigation was to ascertain whether bisphenol A (BPA), which has a structural resemblance to thyroid hormone (TH), acts as a TH agonist or antagonist in terms of affecting the release of thyrotropin (TSH). To this end, we exposed adult bullfrog (Rana catesbeiana) pituitary cells to BPA and/or TH in the presence or absence of corticotropin-releasing factor (CRF), which is known to have a potent TSH-releasing activity in amphibians. BPA (10 (-9)-10 (-4) M) did not affect the basal release of TSH. However, it suppressed CRF-inducible TSH release at 10 (-4) M, but not at 10 (-5) M. Triiodothyronine (T (3)) at 10 (-7) M and l-thyroxine (T (4)) at 10 (-6) M also suppressed the CRF-inducible release of TSH. The combination of T (3) (10 (-7) M) or T (4) (10 (-6) M) with BPA (10 (-4) M) had an additive effect in suppressing TSH release. A comparison of the suppressive effects of BPA and T (3) on the release of TSH following the addition of actinomycin D or cycloheximide to the culture medium revealed that both of the latter compounds blocked T (3)-inducible but not BPA-inducible suppression of TSH release. The results indicate that the mechanism of action of BPA is different from that of T (3) in that T (3) action involves RNA and protein synthesis, whereas BPA action does not involve either of these processes. Furthermore, BPA was found to suppress the thyrotropin-releasing hormone-inducible release of both prolactin (PRL) and TSH. Our results suggest that BPA acts not only as a blocker of TSH secretagogues but also as a blocker of a PRL secretagogue at the pituitary level. Estradiol affected neither the release of TSH nor the release of PRL in the presence or absence of their secretagogues, suggesting that the suppression of the release of TSH and PRL caused by BPA may not be derived from its estrogenic activity. |
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