Anterior Pituitary and Hypothalamus

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Disorders of the Anterior Pituitary and Hypothalamus 
The anterior pituitary is often referred to as the “master gland” because, together with the hypothalamus, it orchestrates the complex regulatory functions of multiple other endocrine glands. The anterior pituitary gland produces six major hormones:
1-   Prolactin(PRL),
2-   Growth hormone (GH),
3-   Adrenocorticotropin hormone (ACTH),
4-   Luteinizing hormone (LH),
5-   Follicle-stimulating hormone (FSH), and
6-  Thyroid-stimulating hormone (TSH).
Pituitary hormones are secreted in a pulsatile manner, reflecting stimulation by an array of specific hypothalamic releasing factors. Each of these pituitary hormones elicits specific responses in peripheral target tissues. The hormonal products of these peripheral glands, in turn, exert feedback control at the level of the hypothalamus and pituitary to modulate pituitary function. Pituitary tumors cause characteristic hormone excess syndromes. Hormone deficiency may be inherited or acquired. Fortunately, efficacious treatments exist for the various pituitary hormone excess and deficiency syndromes. Nonetheless, these diagnoses are often elusive, emphasizing the importance of recognizing subtle clinical manifestations and performing the correct laboratory diagnostic tests.
Pituitary Development
The embryonic differentiation and maturation of anterior pituitary cells have been elucidated in considerable detail. Pituitary development from Rathke’s pouch involves a complex interplay of lineage-specific transcription factors expressed in pluripotent stem cells and gradients of locally produced growth factors. The transcription factor Pit-1 determines cell-specific expression of GH, PRL, and TSH in somatotrophs, lactotropes, and thyrotrophs. Expression of high levels of estrogen receptors in cells that contain Pit-1 favors PRL expression, whereas thyrotrope embryonic factor (TEF) induces TSH expression.
Pit-1 binds to GH, PRL, and TSH gene regulatory elements, as well as to recognition sites on its own promoter, providing a mechanism for perpetuating selective pituitary phenotypic stability. The transcription factor Prop-1 induces the pituitary development of Pit-1-specific lineages, as well as gonadotropes.
Gonadotropes cell development is further defined by the cell-specific expression of the nuclear receptors, Steroidogenic factor (SF-1) and DAX-1. Development of corticotrope cells, which express the proopiomelanocortin (POMC) gene, requires the T-Pit transcription factor. Abnormalities of pituitary development caused by mutations of Pit-1, Prop-1, SF-1, DAX-1, and T-Pit result in a series of rare, selective or combined, pituitary hormone deficits.

Hypothalamic and anterior Pituitary Insufficiency 
Hypopituitarism results from impaired production of one or more of the anterior pituitary trophic hormones. Reduced pituitary function can result from inherited disorders; more commonly, it is acquired and reflects the mass effects of tumors or the consequences of inflammation or vascular damage. These processes may also impair synthesis or secretion of hypothalamic hormones, with resultant pituitary failure.
Development and Genetic Causes of Hypopituitarism 
Pituitary Dysplasia
Pituitary dysplasia may result in aplastic, hypoplastic, or ectopic pituitary gland development. Because pituitary development requires midline cell migration from the nasopharyngeal Rathke’s pouch, midline craniofacial
disorders may be associated with pituitary dysplasia. Acquired pituitary failure in the newborn can also be caused by birth trauma, including cranial hemorrhage, asphyxia, and breech delivery.

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