The next important test was whether this in vitro anterior pituitary anlage would show similar functionality to the physiological activity of the adenohypophysis. Of the many critically important pituitary hormones, they chose adenocorticotropic hormone (ACTH) for their first assay. Previous research had suggested that Notch signaling interferes with the development of ACTH-secreting cells, so the group added a Notch blocker to the culture medium and found that this triggered the generation of such cells at high efficiencies. Following a similar principle, they showed that by adding Wnt, glucocorticoid and insulin to the culture at appropriate doses and stages, they could obtain growth hormone-secreting cells in quantity. By varying the recipe of the growth factor cocktail, they were able to induce other pituitary hormones as well. And, critically, the group was able to show that in vitro hormone secretion could respond to requisite signals and engage in regulatory feedback just as in the body.
In a final series of experiments, Suga et al. transplanted the ESC-derived ACTH-secreting tissue into the kidneys of adult mice whose own pituitary glands had been ablated, to see whether it would be capable of compensating for pituitary function in this model system. Within a week of transplantation, these mice showed strong overall survival, a marked rise in ACTH levels and a concomitant increase in corticosterone (a glucocorticoid hormone stimulated by ACTH) over untransplanted controls, which uniformly weakened and died within eight weeks of hypophysectomy.
Yoshiki Sasai, leader of the study, commented on this most recent demonstration of the remarkable self-organizing capabilities of embryonic stem cells in vitro. "We have previously shown how ES cells can give rise to self-organized, three-dimensional neuronal and sensory tissues, and in this report we describe for the first time how this principle can b
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