The Hypothalamic-Pituitary-Thyroid (HPT) Axis in Frogs and Its Role in Frog Development and Reproduction

Metamorphosis of the amphibian tadpole is a thyroid hormone (TH)-dependent developmental process. For this reason, the tadpole is considered to be an ideal bioassay system to identify disruption of thyroid function by environmental contaminants. Here we provide an in-depth review of the amphibian thyroid system with particular focus on the role that TH plays in metamorphosis. The amphibian thyroid system is similar to that of mammals and other tetrapods. We review the amphibian hypothalamic-pituitary-thyroid (HPT) axis, focusing on thyroid hormone synthesis, transport, and metabolism. We also discuss the molecular mechanisms of TH action, including the role of TH receptors, the actions of TH on organogenesis, and the mechanisms that underlie the pleiotropic actions of THs. Finally, we discuss methods for evaluating thyroid disruption in frogs, including potential sites of action, relevant endpoints, candidate protocols for measuring thyroid axis disruption, and current gaps in our knowledge. The utility of amphibian metamorphosis as a model for evaluating thyroid axis disruption has recently led to the development of a bioassay using Xenopus laevis.