| Corticotropic cell | |
|---|---|
| Details | |
| Location | Anterior pituitary |
| Function | Production ofmelanocyte-stimulating hormone,adrenocorticotropic hormone (ACTH) andlipotropin |
| Identifiers | |
| MeSH | D052680 |
| TH | H3.08.02.2.00009 |
| FMA | 83098 |
| Anatomical terms of microanatomy | |
Corticotropic cells, (corticotropes orcorticotrophs) arebasophiliccells in theanterior pituitary that producepro-opiomelanocortin (POMC) which undergoes cleavage toadrenocorticotropin (ACTH),β-lipotropin (β-LPH), andmelanocyte-stimulating hormone (MSH). These cells are stimulated bycorticotropin releasing hormone (CRH) and make up 15–20% of the cells in the anterior pituitary.[1] The release of ACTH from the corticotropic cells is controlled by CRH, which is formed in the cell bodies ofparvocellular neurosecretory cells within theparaventricular nucleus of thehypothalamus and passes to the corticotropes in the anterior pituitary via thehypophyseal portal system. Adrenocorticotropin hormone stimulates theadrenal cortex to releaseglucocorticoids and plays an important role in thestress response.[2]
The primary function of the corticotropic cells is to produce theprohormone POMC in response to the release of CRH from the hypothalamus. POMC is cleaved into severalpeptide hormones via enzyme activity. In addition to synthesis in the corticotropes, POMC is also synthesized inmelanotroph cells, thearcuate nucleus of the hypothalamus, andmelanocytes.[3] POMC undergoes differential cleavage into various peptide hormones depending on the cell it is synthesized in; it also varies based on species. POMC in the corticotropes of humans is proteolytically cleaved byproprotein convertases into ACTH andβ-lipotropin.[4] In rats, however, the ACTH is further cleaved intoα-MSH andCLIP in the corticotrope.[3] These peptide hormones are stored within vesicles in the corticotropic cells and are released in response to CRH stimulation from the hypothalamus. These vesicles then leave the anterior pituitary and travel throughout the body via the bloodstream to reach their target tissues.[5]
| Hormone(s) | Main Targets | Effects |
|---|---|---|
| ACTH | Adrenal cortex | Glucocorticoid synthesis |
| α-MSH,β-MSH,γ-MSH | Skin Cells (Melanocytes),Brain,Exocrine Glands | Pigmentation of hair and skin,satiety, weighthomeostasis[5] |
| CLIP | Pancreas | Insulin secretagogue, stimulates insulin release[6] |
| β-lipotropin,γ-lipotropin | Adipose Tissue | Lipolysis, fatty acid mobilization[7] |
| β-endorphin | Peripheral Nervous System | Pain management[8] |
Corticotropic cells serve an important role within the feedback loop of thehypothalamic–pituitary–adrenal (HPA) axis and thestress response. Corticotropes produce and release ACTH, a 39amino acidpeptide hormone, in response to corticotropic releasing hormone (CRH) release from the hypothalamus. CRH is a 41-amino-acid peptide hormone that is secreted by theparvocellular neurosecretory cells, which are found within theparaventricular nucleus of the hypothalamus.[9]
Stimuli for the release of CRH from the hypothalamus include:
Forskolin and PACAP regulate the synthesis of CRH in the hypothalamus by binding toG protein-coupled receptors and stimulating and increase incAMP within the cells via the action ofadenylate cyclase. This activates theprotein kinase A pathway, which results in the binding ofcAMP response element binding protein (CREB) onto the CRHpromoter region and inducestranscription of CRH. This process is repressed by glucocorticoids; this inhibitory feedback helps maintain homeostasis of the stress response.[10]
Once released by the hypothalamus, CRH travels through thehypophyseal portal system to the anterior pituitary, where it binds to G protein-coupled receptors on the corticotropic cell membrane and stimulates cAMP production. The effects of CRH on pituitary corticotropes are potentiated byvasopressin (AVP); AVP is a weak inducer of ACTH production on its own, but has a strong synergistic effect on ACTH production when CRH is also bound to the receptor.[11] These signaling hormones act viasignal transduction, causing the synthesis of POMC and eventual cleavage to ACTH and β-lipotropin. These peptide hormones are then released into the bloodstream, where they circulate and act on target tissues.
ACTH released from the corticotropes binds to G protein-coupled receptors in the adrenal cortex, where it stimulates the production ofglucocorticoids (primarilycortisol).[12] ACTH binds to themelanocortin 2 receptor and, through signal transduction, increases levels of cholesterolesterase, the transport ofcholesterol across the mitochondrial membrane, cholesterol binding toP450SCC and, an increase inpregnenolone synthesis.[5] It also serves as a secondary stimulus for the synthesis ofmineralocorticoids such asaldosterone, which serve an important role in regulating the salt balance of the blood.[13] Glucocorticoids released by the adrenal cortex inhibit production of CRH and ACTH, forming anegative feedback loop.[5]
Corticotropes containglucocorticoid receptors (GRs) andcorticosteroid-binding globulin (CBG, or transcortin). GR is anuclear receptor that inhibits transcription of ACTH via a negative glucocorticoid recognition element (GRE) that binds cortisol on POMCDNA, but generally transcortin binds glucocorticoids (including cortisol, cortisone, deoxycortisone, and aldosterone) with high affinity and prevents this inhibition.[14] Tonic inhibition of corticotropes requires high concentrations of glucocorticoids, exceeding CBG capacity. This causes ACTH secretion to be vulnerable to inhibition in patients taking glucocorticoids for medical purposes such as treatment of autoimmune disease or as an anti-transplant-rejection medication.[15]
Corticotropic cells can have detrimental effects on the body if they express too much or too little ACTH. One such example isCushing's disease, which can result from overproduction of ACTH in the corticotropes due to pituitary tumors known as corticotrophadenomas; this is the cause for roughly two-thirds of those diagnosed with Cushing's disease.[16] It is also possible that this disease can result from production of ACTH in a non-pituitary tumor, known as ectopic production, or the adrenal glands can overproduce cortisol due to an adrenal tumor.[17] This overproduction of ACTH causes an increase in cortisol levels due to increased glucocorticoid synthesis in the adrenal cortex resulting in several associated symptoms.
Symptoms of Cushing's disease include:
Corticotropic cells can also be the cause ofAddison's disease in some instances. Addison's disease is characterizedadrenal insufficiency, which is defined as the underproduction of glucocorticoids by the adrenal cortex. If the corticotropes underproduce ACTH this can result in secondary adrenal insufficiency, causing the adrenal glands to underproduce cortisol. This can be caused by tumors of the anterior pituitary or hypothalamus, inflammation, or surgery.[19] This ultimately results in the underproduction of cortisol, which has many detrimental symptoms.
Symptoms of Addison's disease include:
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