Evolution and selective reduction of hormonal secretion in the mammotropic pituitary tumor (MtT-F₄)

Severe hypertensive vascular disease was produced in 1969 in our laboratory by implantation of the mammotropic tumor MtT-F₄, secreting very large amounts of corticotropin, prolactin and growth hormone in Fischer F 344 female rats. The hypertension was caused by adrenal cortical dysfunction with hyperproduction of deoxycorticosterone (DOC), and consequent sodium retention. Ultrastructural changes in the zona fasciculata cells of the adrenal glands were also evident in the tumor-implanted hypertensive rats, thus confirming the impaired adrenal steroidogenesis. The tumor has been maintained in our laboratory by continuous passages from rat to rat or it was being stored frozen for 3 years and then reimplanted. Implants with these new strains of tumor resulted in marked reduction or total loss of its hypertensinogenic ability. In addition to the failure to develop hypertension, the same strains of tumor also showed a reduced secretion of corticotropin, reflected in a smaller increase of the adrenal weight, a smaller reduction of thymic weight and a less marked sodium retention with normal levels of plasma sodium. The less elevated secretion of corticotropin was also indicated by a more normal ultrastructural appearance of the zona fasciculata cells. No alterations in the tumor secretion of growth hormone and prolactin was evident with the continuous passage from rat to rat, at least judging from the effect of the two hormones on their target organs. It is still controversial as to whether a synergistic action of corticotropin, growth hormone and prolactin is necessary in order to cause severe hypertensive vascular disease in the rats implanted with the mammotropic tumor. However, the present experiment has outlined, that among the three hormones secreted, corticotropin definitely plays a major role in the development of such disease.