Endocrine cells of the mammalian pituitary gland release systemic hormones, such as adenocorticotropic hormone (ACTH), luteinizing hormone, follicle-stimulating hormone and prolactin, in response to signals from the adjacent hypothalamus. During development the gland emerges from the rostral head ectoderm, and its elaborate organisation depends on interactions with adjacent neural tissues. By partly reproducing these interactions in vitro, Sasai and colleagues obtained a functional pituitary gland from embryonic stem cells (Nature 480, 57–62; 2011).

The authors determined that aggregation of many embryonic stem cells in the presence of BMP4 led to the simultaneous differentiation of an epithelium with characteristics of the rostral head ectoderm overlaying a hypothalamic neuroectodermal cell layer. Following addition of Hedgehog agonists (known to promote pituitary gland fate in vivo), hollow epithelial structures formed in which the cells adopted the polarity and organisation characteristic of the pituitary gland. Inhibiting Notch signalling in these cultures was then sufficient to induce the differentiation of distinct endocrine cell types. As observed in vivo, ACTH release from these cells was induced by the gonadotropin hormone and inhibited by glucocorticoids. Finally, following ablation of the pituitary gland in mice, the authors transplanted the aggregates into kidney capsules and observed restored blood ACTH levels, as well as the physiological activities dependent on this hormone. Whether these transplanted aggregates show the plasticity that characterises the pituitary gland, which dynamically changes its proportions of endocrine cells in response to physiology, remains to be explored.