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Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Xenopus Metamorphosis
STERNBERG, R., K. R. THOEMKE, J. J. KORTE, S. M. MOEN, J. OLSON, L. KORTE, J. E. TIETGE, AND S. J. DEGITZ. Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Xenopus Metamorphosis. GENERAL AND COMPARATIVE ENDOCRINOLOGY. Academic Press Incorporated, Orlando, FL, 173(3):428-437, (2011).
To document research results.
Serum thyroid hormone (TH) concentrations in anuran larvae rise rapidly during metamorphosis. Such a rise in an adult anuran would inevitably trigger a negative feedback response resulting in decreased synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary. However, pituitary TSH mRNA expression also increases during metamorphosis in concert with serum TH concentrations. If negative feedback by THs on the pituitary is operative during metamorphosis, how TSH production and circulating TH concentrations rise concomitantly during this transformative process is still unclear. We used ex vivo and in vivo experiments with Xenopus laevis tadpoles to examine the hypothesis that the set-point for negative feedback on pituitary TSH synthesis and secretion by TH increases during metamorphosis to allow for this seemingly paradoxical, concurrent increase in TH concentrations and TSH synthesis. First, pituitaries from climatic tadpoles were collected immediately or cultured for up to 96 hours to characterize the ability of pituitary explants to synthesize and secrete TSH in the absence of THs. Next, pituitaries from metamorphic tadpoles (NF stages 54 66) were cultured in the absence (control) or presence of 1 or 10 nM T4 or T3 to determine whether stage-specific differences exist in pituitary sensitivity to negative feedback by THs. Finally, tadpoles were reared in water containing the same concentrations of T4 or T3 as those used in the ex vivo experiments to confirm the results found in the pituitary explant cultures. Pituitaries were collected and analyzed for TSH mRNA expression and intracellular TSH protein, and media was collected and analyzed for secretion of TSH protein. When pituitaries from climatic tadpoles were removed from the influence of endogenous THs, TSHb mRNA expression increased late or not at all whereas TSH secretion increased dramatically suggesting that TSH mRNA expression is not necessarily under the negative regulation of an endogenous signal during the climatic stages of metamorphosis. However, TSH secretion may still be negatively regulated by an endogenous signal during these same stages. Pituitaries from pre- and prometamorphic tadpoles were more sensitive to TH-induced inhibition of TSH synthesis and release than pituitaries from climatic tadpoles. This observed decrease in sensitivity of pituitary TSH synthesis to negative feedback by THs from premetamophosis to metamorphic climax was confirmed by in vivo experiments in which tadpoles were reared in water containing T3 or T4. Collectively, this ex vivo and in vivo data provide support for our moving set-point hypothesis for TH negative feedback on pituitary TSH synthesis and secretion during metamorphosis.