Impaired Development of Somatotropes, Lactotropes and Thyrotropes in Growth-Retarded (grt) Mice

Congenitally primary hypothyroid growth-retarded (grt) mice exhibit a characteristic growth pause followed by delayed onset of pubertal growth. We characterized the developmental pattern of somatotropes, lactotropes and thyrotropes in the anterior pituitary, as well as plasma levels of their secretory hormones, in grt mice. Compared with normal mice, the weight of grt pituitary gland was similar at 8 weeks of age but significantly heavier after 12 weeks of age. Compared with normal mice, there were significantly fewer somatotropes in the grt pituitary until 8 weeks of age, but the number gradually increased up to 48 weeks. The number of lactotropes in grt mice was consistently lower than that in normal mice from 2 through 48 weeks, whereas the number of thyrotropes in the grt pituitary was consistently higher than in the normal pituitary. Thyrotropes in the grt pituitary exhibited hypertrophy and hyperplasia with less intensive thyroid-stimulating hormone (TSH) immunoreactivity than normal thyrotropes. In normal mice, the sum of the relative proportions of these cells plateaued at 8 weeks, where it remained up to 48 weeks of age. In grt mice, these proportions almost reached normal levels at 12 weeks of age but gradually declined after 24 weeks. Plasma growth hormone concentrations did not differ between grt and normal mice until 24 weeks of age. Compared with normal mice, grt mice exhibited significantly lower plasma prolactin and thyroxine levels but higher TSH levels. These findings indicate that development of somatotropes, lactotropes and thyrotropes in grt mice is impaired, being followed by altered hormone secretion.