Chief cell

In human anatomy, there are three types of chief cells, the gastric chief cell, the parathyroid chief cell, and the type 1 chief cells
found in the carotid body.

Contents
Cell types
Histology
Diseases
References

Cell types
The gastric chief cell (also known as a zymogenic cell or peptic cell) is a cell in the stomach that releases pepsinogen[1] and
chymosin. Pepsinogen is activated into the digestive enzyme pepsin when it comes in contact with acid produced by gastric
parietal cells.[2] This type of cell also secretes gastric lipase enzymes, which help digest triglycerides into free fatty acids and di-
and mono-glycerides.[3] There is also evidence that the gastric chief cell secretes leptin in response to the presence of food in the
stomach. Leptin has been found in the pepsinogen granules of chief cells.[4]

Gastric pit cells are replaced every 2–4 days. This high rate of turnover is a protective mechanism designed to protect the
epithelial lining of the stomach from both the proteolytic action of pepsin and the acid produced by parietal cells.[5] Gastric chief
cells are much longer lived and are believed to differentiate from stem cells located higher in the gastric unit in the isthmus.[1]
These stem cells differentiate into mucous neck cells in the isthmus and transition into chief cells as they migrate towards the
base. Since the mucus neck cells do not divide as it becomes a chief cell this process is known as transdifferentiation.[6] The gene
Mist1 has been shown to regulate mucus neck cell to chief cell transdifferentiation and plays a role in the normal development of
the chief cell organelles and structures.[6]

The parathyroid chief cell is the primary cell of the parathyroid gland. It produces and secretes parathyroid hormone in response
to low calcium levels. PTH plays an important role in regulating blood calcium levels by raising the amount of calcium in the
blood.[7] Parathyroid tissue seems to have a low turn-over rate.[8]

Histology
Gastric chief cells are epithelial cells which are found within the gastric unit or gastric gland, and form the base of the gastric
unit.[9] The gastric chief cell has an extensive network of lamellar rough endoplasmic reticulum organized around the nucleus.
The gastric chief cell also contains many large secretory vesicles filled with digestive enzymes in the apical cytoplasm.[6]

Parathyroid chief cells make up the majority of the parathyroid gland along with adipocytes and oxyphil cells. Parathyroid chief
cells have large amounts of organelles associated with protein synthesis. As in many endocrine organs, with age, more oxyphil
cells appear in the parathyroid gland.[10]

Diseases
In gastric tissue, a loss of parietal cells due to chronic inflammation has been shown to affect chief cell differentiation and can
induce chief cells to transdifferentiate back into neck cells and can lead to the formation of mucus cell metaplasia known as
spasmolytic polypeptide expressing metaplasia (SPEM) that could be precancerous.[11] If parietal cells are lost, mature chief cells
do not form. Parietal cells may secrete factors that lead to transdifferentiation of chief cells, so if lost, chief cells do not normally
develop.[12]

References
1. Ramsey, VG; Doherty, JM; Chen, CC; Stappenbeck, TS; Konieczny, SF; Mills, JC (Jan 2007). "The maturation of
mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1".
Development. 134 (1): 211–22. doi:10.1242/dev.02700 (https://doi.org/10.1242%2Fdev.02700). PMID 17164426
(https://www.ncbi.nlm.nih.gov/pubmed/17164426).
2. MeSH https://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?mode=&term=Chief+Cells,+Gastric&field=entry
3. http://www.copewithcytokines.de/cope.cgi?key=chief%20cells
4. Picó, C; Oliver, P; Sánchez, J; Palou, A (Oct 2003). "Gastric leptin: a putative role in the short-term regulation of
food intake". The British Journal of Nutrition. 90 (4): 735–41. doi:10.1079/BJN2003945 (https://doi.org/10.1079%
2FBJN2003945). PMID 13129441 (https://www.ncbi.nlm.nih.gov/pubmed/13129441).
5. Boron, WF; Waisbren, SJ; Modlin, IM; Geibel, JP (Nov 1994). "Unique permeability barrier of the apical surface of
parietal and chief cells in isolated perfused gastric glands". The Journal of Experimental Biology. 196: 347–60.
PMID 7823033 (https://www.ncbi.nlm.nih.gov/pubmed/7823033).
6. Goldenring, JR; Nam, KT; Mills, JC (Nov 15, 2011). "The origin of pre-neoplastic metaplasia in the stomach: chief
cells emerge from the Mist" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210373). Experimental Cell
Research. 317 (19): 2759–64. doi:10.1016/j.yexcr.2011.08.017 (https://doi.org/10.1016%2Fj.yexcr.2011.08.017).
PMC 3210373 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210373). PMID 21907708 (https://www.ncbi.nlm.
nih.gov/pubmed/21907708).
7. Fabbri, S; et al. (2010). "P12 - PTHC1: A Continuing Cell Line Expressing PTH and Genes Involved in Calcium
Homeostasis" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213842). Clinical Cases in Mineral and Bone
Metabolism. 7 (3): 207–240. PMC 3213842 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213842).
8. Costa-Guda, J; Tokura, T; Roth, SI; Arnold, A (Oct 4, 2007). "Mitochondrial DNA mutations in oxyphilic and chief
cell parathyroid adenomas" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2099428). BMC Endocrine Disorders.
7: 8. doi:10.1186/1472-6823-7-8 (https://doi.org/10.1186%2F1472-6823-7-8). PMC 2099428 (https://www.ncbi.nl
m.nih.gov/pmc/articles/PMC2099428). PMID 17916247 (https://www.ncbi.nlm.nih.gov/pubmed/17916247).
9. Khan, AR; James, MN (Apr 1998). "Molecular mechanisms for the conversion of zymogens to active proteolytic
enzymes" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2143990). Protein Science. 7 (4): 815–36.
doi:10.1002/pro.5560070401 (https://doi.org/10.1002%2Fpro.5560070401). PMC 2143990 (https://www.ncbi.nlm.
nih.gov/pmc/articles/PMC2143990). PMID 9568890 (https://www.ncbi.nlm.nih.gov/pubmed/9568890).
10. "Archived copy" (https://web.archive.org/web/20120409004830/http://instruction.cvhs.okstate.edu/histology/histol
ogyreference/hrendo.htm). Archived from the original (http://instruction.cvhs.okstate.edu/histology/histologyrefere
nce/hrendo.htm) on 2012-04-09. Retrieved 2012-04-15.
11. Bredemeyer, Andrew J.; Geahlen, Jessica H.; Weis, Victoria G.; Huh, Won Jae; Zinselmeyer, Bernd H.;
Srivatsan, Subhashini; Miller, Mark J.; Shaw, Andrey S.; Mills, Jason C. (1 January 2009). "The gastric epithelial
progenitor cell niche and differentiation of the zymogenic (chief) cell lineage" (https://www.ncbi.nlm.nih.gov/pmc/a
rticles/PMC2634829). Developmental Biology. 325 (1): 211–224. doi:10.1016/j.ydbio.2008.10.025 (https://doi.org/
10.1016%2Fj.ydbio.2008.10.025). PMC 2634829 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634829).
PMID 19013146 (https://www.ncbi.nlm.nih.gov/pubmed/19013146).
12. Nam, KT; Lee, HJ; Sousa, JF; Weis, VG; O'Neal, RL; Finke, PE; Romero-Gallo, J; Shi, G; Mills, JC; Peek RM, Jr;
Konieczny, SF; Goldenring, JR (Dec 2010). "Mature chief cells are cryptic progenitors for metaplasia in the
stomach" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997152). Gastroenterology. 139 (6): 2028–2037.e9.
doi:10.1053/j.gastro.2010.09.005 (https://doi.org/10.1053%2Fj.gastro.2010.09.005). PMC 2997152 (https://www.
ncbi.nlm.nih.gov/pmc/articles/PMC2997152). PMID 20854822 (https://www.ncbi.nlm.nih.gov/pubmed/20854822).
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