Endocrine Abstracts

The pituitary gland is a central regulator of growth, homeostasis and reproduction. It is in turn regulated by the hypothalamus, which generates a number of releasing factors (GHRH, TRH, GnRH, CRH) and the inhibitory hormone somatostatin. The pituitary gland consists of the anterior and posterior lobes, both of which have separate developmental origins. The anterior lobe derives from the oral ectoderm, whilst the posterior lobe derives from the neuroectoderm. The anterior pituitary contains five different cell types secreting six different hormones, namely GH, prolactin, TSH, ACTH, LH and FSH. The posterior pituitary secretes vasopressin and oxytocin.

Normal hypothalamo-pituitary development is closely related to that of the forebrain, and is dependent upon a complex genetic cascade of transcription factors and signalling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes due to mutations in genes encoding both signalling molecules and transcription factors are associated with congenital hypopituitarism, a spectrum of disorders that includes septo-optic dysplasia (SOD), combined pituitary hormone deficiencies (CPHD), and isolated hormone deficiencies, of which the commonest is GH deficiency (IGHD). These include HESX1, LHX3, LHX4, PROP1 POU1F1 and, more recently, GLI2, OTX2, SOX3 and SOX2. Phenotypes associated with mutations in genes encoding these factors may be highly variable, as may the inheritance. Genes that are implicated in early pituitary development are more likely to be associated with complex phenotypes, whilst those expressed later have more defined phenotypes.

To conclude, normal pituitary ontogeny in mouse and human is the result of a carefully orchestrated genetic cascade. To date, genetic mutations account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to pituitary development. It is also likely that mutations will be identified in other genes that are implicated in normal pituitary development.