(2001).ĭeiodinase type 2 plays an important role in TH-negative feedback on TSH in mammals ( Schneider et al., 2001 St Germain, Hernandez, Schneider, & Galton, 2005). Taken together, these findings support that negative feedback at the level of the pituitary is active in the premetamorphic and early prometamorphic tadpole, which does not support Etkin's hypothesis and contradicts Huang et al. (2005) found that CRF-induced TSH release by bullfrog primary pituitary cells was suppressed by T 3 throughout metamorphosis. Pituitary sensitivity to negative feedback by TH may decline slightly during late prometamorphosis and metamorphic climax, perhaps due to the upregulation of pituitary Dio3 at this time ( Manzon & Denver, 2004 Sternberg et al., 2011). laevis tadpoles throughout metamorphosis to suppress tshβ mRNA expression and TSH secretion ( Manzon & Denver, 2004 Sternberg et al., 2011). Physiological concentrations of T 4 or T 3 can act directly on pituitary explants of X. Further, goitrogen treatment of premetamorphic tadpoles caused a dramatic elevation in tshβ mRNA ( Buckbinder & Brown, 1993 Huang et al., 2001). For example, treatment of premetamorphic tadpoles with goitrogens caused enlargement of the thyroid gland and degranulation of pituitary thyrotropes, while replacement with T 4 reversed the effects, suggesting that negative feedback was functional in the premetamorphic tadpole ( Dodd & Dodd, 1976 Goos, 1968, 1978 Goos, Deknecht, & Devries, 1968).

However, many investigators have found that negative feedback by TH on TSH is active in the premetamorphic and early prometamorphic tadpole. (2001) proposed that the onset of negative feedback at metamorphic climax was coincident with the expression of Dio2 in the tadpole pituitary.

The discovery of a sustained rise in TSH production and thyroid activity during tadpole metamorphosis led Etkin (1968) to hypothesize that negative feedback on pituitary TSH does not develop until metamorphic climax. Negative feedback by TH on the hypothalamus and pituitary plays a central role in thyroid homeostasis in all adult vertebrates that have been studied including frogs ( Fig. Denver, in Current Topics in Developmental Biology, 2013 2.1.1 Feedback regulation of TSH