Growth factors and the anterior pituitary

Normal growth and secretion in the pituitary gland are dependent upon the co-ordinated action of a large number of extracellular growth factors, neuropeptides and peripheral hormones acting on their respective cellular receptors and via complex intracellular signalling pathways. The pituitary and hypothalamus are exposed to a large number of growth factors, several of which have well-documented effects on secretory function and may act as physiological modulators of pituitary hormone synthesis and release. IGF-I, for example, almost certainly acts as a feedback regulator of GH secretion. Despite well-documented mitogenic effects in other tissues, little is known about the role of these growth factors in normal pituitary cell turnover, compensatory hyperplasia or adenoma formation. There is now good evidence, however, that at least some of the hypothalamic releasing peptides are mitogenic for their respective pituitary cell subpopulations. The aetiology of pituitary tumours remains poorly understood but some appear to develop as a result of somatic mutation. Such mutations could enhance growth by causing altered expression of growth factors or their receptors, or constitutive activation of proteins involved in the intracellular mitogenic signal. Abnormalities have been documented at each of these levels in human pituitary tumours. The identification of an activating point mutation in the alpha subunit of Gs, the stimulatory regulatory peptide of adenylyl cyclase, in a proportion of somatotroph adenomas represents a major advance in our understanding of pituitary tumour pathogenesis. This and other findings may ultimately lead to new therapeutic approaches to the management of pituitary disease.