Thyroid hormone is essential for pituitary somatotropes and lactotropes

Mice homozygous for a disruption in the alpha-subunit essential for TSH, LH , and FSH activity (alpha Gsu(-/-)) exhibit hypothyroidism and hypogonadism similar to that observed in TSH receptor-deficient hypothyroid mice (hyt) and GnRH-deficient hypogonadal mutants (hpg). Although the five major hormo ne-producing cells of the anterior pituitary are present in alpha Gsu(-/-) mice, the relative proportions of each cell type are altered dramatically. Thyrotropes exhibit hypertrophy and hyperplasia, and somatotropes and lacto tropes are underrepresented. The size and number of gonadotropes in alpha G su mutants are not remarkable in contrast to the hypertrophy characteristic of gonadectomized animals. The reduction in lactotropes is more severe in alpha Gsu mutants (13-fold relative to wild-type) than in hyt or hpg mutant s (4.5- and 1.5-fold, respectively). In addition, T-4 replacement therapy o f alpha Gsu mutants restores lactotropes to near-normal levels, illustratin g the importance of T-4, but not alpha-subunit, for lactotrope proliferatio n and function. T-4 replacement is permissive for gonadotrope hypertrophy i n alpha Gsu mutants, consistent with the role for T-4 in the function of go nadotropes. This study reveals the importance of thyroid hormone in develop ing the appropriate proportions of anterior pituitary cell types.