Mesenchymal influences on the development of the adenohypophysis in the rat

Comparative studies have been made of development of the adenohypophysis using the Rathke's pouch (RP)-derived model system. Rathke's pouch with associated mesenchyme and ventral hypothalamus, was microsurgically isolated from 15-day fetal rats and placed in mild trypsin solution. Three variations of donor tissue were isolated and transplanted beneath the kidney capsule of adult hosts: A) pure pouch epithelium; B) pouch epithelium plus mesenchyme; and C) pouch epithelium with mesenchyme and ventral hypothalamus. After 30 days the grafts were isolated and processed for light and electron microscopy. Cell types were characterized by immunostaining as well as by morphological criteria. In group A well differentiated mammotrophs dominated the grafts, many of which were hypertrophied with widely dilated endoplasmic reticulum and Golgi saccules. Mammotrophs, frequently with mitotic figures, were distributed evenly throughout the grafts. Somatotrophs and gonadotrophs were neither abundant nor well differentiated in group A, but were both abundant and more extensively differentiated in groups B and C. Both somatotrophs and gonadotrophs were typically localized at margins of the graft adjacent to connective tissue spaces. Well differentiated mammotrophs were present in groups B and C although there were fewer hypertrophied mammotrophs than in group A; and immunoreaction to prolactin was weaker than in group A. Tumor-like features found in all three groups included some loss of tissue integrity and large, vascular lakes unlined by endothelium. These findings suggest that differentiation of mammotrophs may be inhibited in part by mesenchyme associated with Rathke's pouch, since in the absence thereof these cells become hyperplastic. Conversely, differentiation of somatotrophs and gonadotrophs appears more dependent on these mesenchymal elements for normal development.