MANZON, R.G.*; DENVER, R.J.; University of Regina, SK, Canada; University of Michigan, Ann Arbor, USA: Regulation of pituitary thyrotropin during Xenopus metamorphosis: beyond type II deiodinase.
Several hypotheses have been proposed to explain the paradoxical increase and sustained expression of pituitary thyrotropin (TSH) in the presence of elevated thyroid hormone (TH) levels at metamorphic climax in amphibians. Huang and Brown (2001; PNAS 98:7348) claimed that the negative feedback of TH on TSH is established only at climax by the upregulation of pituitary deiodinase type II (DII); DII converts thyroxine (T4) to triiodothyronine (T3). To understand pituitary TSH regulation during Xenopus laevis metamorphosis, we analyzed multiple pituitary genes known or suspected to be involved in TSH regulation. Tadpole pituitary explant cultures were used to examine direct negative feedback on TSH mRNA expression. Our data support the hypothesis that the regulation of TSH is more complex than just the expression of DII, and likely involves a balance between stimulation of TSH synthesis and secretion by neuropeptides (e.g. corticotropin releasing hormone [CRH] and thyrotropin releasing hormone [TRH]), increased pituitary sensitivity to neuropeptides, and intrapituitary TH levels. Negative feedback is operative in the premetamorphic tadpole pituitary and both T3 and T4 can downregulate TSH mRNA expression throughout metamorphosis. The expression of both DII and TH receptor βA mRNAs increased during development and peaked at climax; however, these increases coincided with similar increases in deiodinase type III which inactivates TH. Moreover, CRH-receptors, CRH binding protein and TRH receptor type 2 mRNA expression also peaked at climax. These findings suggest that pituitary sensitivity to neuropeptide stimulation of TSH increases at climax. Supported by an NSERC PDF to RGM and NSF grant IBN 9974672 to RJD.
