Fig. 6.

Model for thyrotroph function and response to hypothyroidism in the presence or absence of PITX2. Pituitary thyrotrophs secrete sufficient TSH in adult mice to maintain a euthyroid state in the presence or absence of Pitx2. Pitx1 transcript levels are elevated in the absence of Pitx2, suggesting the possibility of a compensatory role for Pitx1. The pituitary thyrotrophs of both normal and Pitx2-deficient mice produce additional TSH in response to hypothyroidism induced by PTU, but the response is blunted in Pitx2-deficient mice. Hypothyroidism causes a dramatic increase in Pitx1 transcription in normal mice, but Pitx1 transcript levels do not increase further in Pitx2-deficient mice, possibly because an additional increase in Pitx1 transcription is not achievable. These observations support the hypothesis that Pitx1 and Pitx2 have overlapping roles in thyrotrophs, and that Pitx1 is of major importance in response to hypothyroidism.