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Abstract

The pituitary is a complex gland and is composed of several cell types, each responsible for the production of specific hormones. In the past, it was thought that one cell could make only one hormone; the concept of plurihormonality was poorly understood. Plurihormonal adenomas were thought to be either composed of multiple cell types, each producing one hormone (plurimorphous adenomas) or composed of poorly differentiated cells that exhibited abnormal production of multiple hormones. However, the molecular factors that determine hormone production have now been identified as transcription factors that target specific hormone genes. These factors have clarified three main pathways of cell differentiation. ACTH-producing corticotrophs are determined by corticotropin upstream transcription-binding element (CUTE) proteins including neuroD1/beta 2. Bihormonal gonadotrophs require expression of steroidgenic factor (SF)-1. The complex family of Pit-1 expressing cells can mature into somatotrophs, mammosomatotrophs, lactotrophs or thyrotrophs with the additional expression of estrogen receptor (ER) alpha, which enhances PRL secretion, or thyrotroph embryonic factor (TEF) which stimulates TSH-beta production. The recognition of these molecular determinants of adenohypophysial cytodifferentiation has clarified the patterns of plurihormonality which have been recognized in pituitary adenomas and provide a framework for classification of these tumors.

Central Ghrelin Affects Pituitary-Thyroid Axis: Histomorphological and Hormonal Study in Rats

“…Therefore, it is possible that ghrelin treatment could promote transdifferentiation of a multiresponsive and polyhormonal TSH cell subpopulation [43, 44] to GH and/or PRL cells, thus contributing to the decrease in volume density of pituitary thyrotrophs detected under our experimental conditions. Further double immunostaining studies are needed to confirm this hypothesis.…”

An essential role for the hematopoietic transcription factor Ikaros in hypothalamic–pituitary-mediated somatic growth

“…Other examples of pituitary dwarf phenotypes associated with somatotroph deficiency include mutations in the Pit1 transcription factor or its regulator, PROP1 (prophet of Pit1) (19)(20)(21). These mutations result in combined loss of all Pit1-target hormones, GH, PRL, and TSH.…”

Selection and validation of reliable reference genes for RT-qPCR analysis in a large cohort of pituitary adenomas

“…ERα is known to be a transcription factor in gonadotroph and lactotroph cell differentiation (53). Hence, the IRS for ERα was significantly higher in the gonadotroph subgroup than in the corticotroph and null-cell subgroup.…”

“…The different immunohistochemical subtypes of clinically NFPAs are known to have different clinical characteristics, and some of them equivalent to their functioning counterparts (11). The receptor distribution differs between the normal pituitary cells, though not all have been thoroughly studied (52,53). Medical therapies directed towards the somatostatin receptors (SSTR) are available for GH, ACTH and TSH secreting adenomas (54)(55)(56), and towards the dopamine receptor (DR) for prolactin secreting adenomas (57).…”

“…Both are found in normal pituitary tissue (76,77). ER is a known transcription factor for the gonadotroph and lactotroph lineage of pituitary cell development, and has been demonstrated in normal gonadotroph and lactotroph cells (53). There are two classes of Oestrogen receptor, ERα and ERβ, with several isoforms identified for each class (78).…”