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Disorders of pituitary morphogenesis and differentiation

Publication at First Faculty of Medicine, Faculty of Physical Education and Sport, Second Faculty of Medicine, Third Faculty of Medicine, Faculty of Medicine in Hradec Králové |
2006

Abstract

The pituitary gland is the most complex endocrine organ. It plays the key role in growth, reproduction and in the control of composition of body fluids.

Pituitary function is governed by signals from central nervous system transmitted through hypo-thalamus. The additional modulation is based on a feet-back system from peripheral tissues.

A mature, fully differentiated pituitary consists of anterior lobe (anterior pituitary) and of posterior lobe (posterior pituitary). In man, a small intermediate lobe vanishes during pituitary development.The basis for posterior pituitary are axonal endings of hypothalamic neurosecretory neurones that store and release vaso-presine and oxytocine into the bloodstream.

These axons are surrounded by a network of glial cells.Anterior pituitary consists of five main cell lineages according to their hormonal activity. ACTH is produced by corticotrophs,TSH by thyreotrophs, FSH and LH by gonadotrophs, growth hormone by somatotrophs and prolactin by lactotrophs.During embryonic and early foetal development, the pituitary is formed from anterior neuronal ridge (early posterior pituitary) and from the Rathke's pouch that origins from oral ectoderm (early anterior pituitary).

This process is orchestratedby transciption factors HESX1, PITX2, LHX-3 (P-LIM) and LHX-4. Their defects are characterised by combined pituitary hormone deficiency in association with additional developmental defects.The subsequent differentiation and function of single specialised pituitary cell lines is governed by transcription factors PROP1 and POU1F1 (PIT1).

Additionally, SF-1, DAX-1 and KAL1 are essential for the differentiation of gonadotrophs and PITX1, T-PIT and NEUROD1 for corticotrophs. Any single defect of the entire transcription factors leads to specific endocrine phenotype