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Expression of Pituitary Hormones in the Pax8–/– Mouse Model of Congenital Hypothyroidism

Max-Planck-Institut für experimentelle Endokrinologie (S.F., S.C., H.H., K.B.), D-30625 Hannover, Germany; Institut für Anatomie und Zellbiologie (M.K.H.S.), Philipps-Universität Marburg, D-35407 Marburg, Germany; National Hormone and Peptide Program (A.F.P.), Torrance, California; and Department of Internal Medicine (T.J.V.), Erasmus University Medical School, NL-3000 DR Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Dr. Karl Bauer, Department of Neuroendocrinology, Max-Planck-Institut für experimentelle Endokrinologie, Feodor-Lynen-Strasse 7, D-30625 Hannover, Germany. E-mail: karl.bauer{at}mpihan.mpg.de.

Signaling mechanisms in pituitary morphogenesis as well as pituitary cell fate determination during early embryonic development are relatively well characterized. In contrast, the cues that determine the progression of the various anterior pituitary cell types during postnatal periods are poorly defined. Pax8-/- mice, which are born without a thyroid gland, were used to study the influence of thyroid hormones on the expression of pituitary hormones during early postnatal life. Serum pituitary hormones were determined by RIAs, and the pituitaries were analyzed by Northern blotting, in situ hybridization histochemistry, and immunocytochemistry. In 21-d-old Pax8-/- mice, the cellular composition of the anterior pituitary was dramatically distorted. Thyrotropes exhibited hypertrophy and hyperplasia, the number of detectable somatotropes was drastically reduced, and lactotropes were almost undetectable. Expression of LH and FSH was also reduced, but ACTH and proopiomelanocortin expression was not significantly different. Serum pituitary hormone levels were changed correspondingly. T₄ replacement therapy for variable time periods normalized TSH and GH mRNA expression within 3 d but not prolactin expression, not even when T₄ was administered for 6 d in combination with estradiol. These findings reveal the importance of thyroid hormones in developing the appropriate proportions of anterior pituitary cell types, especially with regard to lactotropes.

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