Abstract
The hypothalamic–pituitary–adrenal (HPA) axis plays a critical role in adaptive stress responses and maintaining organism homeostasis. The pituitary corticotroph is the central player in the HPA axis and is regulated by a plethora of hormonal and stress related factors that synergistically interact to activate and temper pro-opiomelanocortin (POMC) transcription, to either increase or decrease adrenocorticotropic hormone (ACTH) production and secretion as needed. Nuclear receptors are a family of highly conserved transcription factors that can also be induced by various physiologic signals, and they mediate their responses via multiple targets to regulate metabolism and homeostasis. In this review, we summarize the modulatory roles of nuclear receptors on pituitary corticotroph cell POMC transcription, describe the unique and complex role these factors play in hypothalamic–pituitary–adrenal axis (HPA) regulation and discuss potential therapeutic targets in disease states.
Highlights
The pituitary gland serves as a critical anatomical and functional connection between central and multiple peripheral endocrine organs (Figure 1A)
(2 mg/kg/day for 180 days) in 22 dogs with Cushing Disease (CD) led to a significant reduction in plasma adrenocorticotropic hormone (ACTH) and α-MSH at 90 days of treatment compared to baseline values (p < 0.01), and reduced corticotroph tumor size at 180 days with improved clinical signs and increased survival time [44]
Chicken ovalbumin upstream promoter transcription factors (COUP-TFs) are highly conserved across species [149] and bind promiscuously to a wide range of direct GGTCA repeat with different spacing and orientations, repressing gene expression either by active repression or by competition for binding sites of other transcription factor [46,150]
Summary
The pituitary gland serves as a critical anatomical and functional connection between central and multiple peripheral endocrine organs (Figure 1A). The posterior pituitary is a direct extension of the hypothalamic magnocellular neurons (MN) of the paraventricular and supraoptic nuclei (PVN and SON) which travel downward along the pituitary stalk (Figure 1B). It stores and releases arginine vasopressin hormone (AVP) and oxytocin (OXT) which maintain water balance and regulate parturition and breast milk release respectively. (AVP), which which are hypothalamic corticotropin-releasing hormone and produced in the paraventricular nucleus (PVN) of the hypothalamus and transported to the anterior pituitary, where drive synthesize and and secretion of pituitary adrenocorticotropic hormonehormone (ACTH). Cells 2020, 9, x; doi: FOR PEER REVIEW www.mdpi.com/journal/cells x FOR PEER REVIEW
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