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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.

Due to the lack of a radioimmunoassay (RIA) system for amphibian thyrotropin (TSH), no direct evidence that thyroid hormone suppresses the release of TSH from the amphibian pituitary has been obtained. However, we recently developed an RIA for bullfrog (Rana catesbeiana) TSH and thus were able to study the effect of thyroid hormone on the release of TSH from the bullfrog pituitary. Enzymatically dispersed pituitary cells of larval, juvenile, and adult bullfrogs were cultured in the absence or presence of 100 nM corticotropin-releasing factor of bullfrog origin (fCRF), which is known to be a potent stimulator of the release of TSH. The amount of spontaneously released TSH was higher in late prometamorphic and climactic tadpoles than in early prometamorphic larvae and juvenile and adult frogs. Pituitary cells from tadpoles at metamorphic climax responded to fCRF to release much more TSH than those from early and late prometamorphic tadpoles and juvenile and adult frogs. In all cases, the fCRF (100 nM)-induced, but not the basal, release of TSH was significantly suppressed by 1 nM triiodothyronine (T(3)) and 1000 nM thyroxine (T(4)), when examined using adult pituitary cells. The suppressive effect of thyroid hormones was revealed to be dependent on their concentrations.