Neuroendocrinology of Amphibian Metamorphosis

The timing of metamorphosis is a central amphibian life history trait and is controlled by the interplay of developmental progression, body size and condition, and environmental signals. These different processes and signals are integrated by the neuroendocrine system to regulate production of hormones by the thyroid gland. Thyroid hormone (TH) is the primary morphogen controlling metamorphosis, while corticosteroids (CSs) produced by the interrenal glands synergize with TH to promote metamorphic changes. The actions of TH are modulated by monodeiodinase enzymes expressed in TH target tissues. CSs act by sensitizing tissues to the actions of TH via the upregulation of TH receptors and monodeiodinases. The increase in thyroid gland activity during metamorphosis is controlled by the hypothalamus and pituitary gland. The hypothalamo-pituitary-thyroid and hypothalamo-pituitary-internal axes are regulated at multiple levels. Hypothalamic corticotropin-releasing factor (CRF) functions as a common, central regulator of pituitary thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) secretion in tadpoles. CRF neurons transduce the signals of environmental change (e.g., pond drying, resource availability, etc.) on metamorphic timing by regulating TSH and ACTH secretion, and consequently the production of TH and CS.