Prorenin

Prorenin (/prəˈriːnɪn/[1]) is a protein that constitutes a precursor for renin,[2] the hormone that activates the renin–angiotensin system, which serves to raise blood pressure. Prorenin is converted into renin by the juxtaglomerular cells, which are specialised smooth muscle cells present mainly in the afferent, but also the efferent, arterioles of the glomerular capillary bed.

Prorenin is a relatively large molecule, weighing approximately 46 KDa.[3]

History

Prorenin was discovered by Eugenie Lumbers[4] in 1971.[5]

Synthesis

In addition to juxtaglomerular cells, prorenin is also synthesised by other organs, such as the adrenal glands, the ovaries, the testis and the pituitary gland, which is why it is found in the plasma of anephric individuals.[6]

Concentration

Blood concentration levels of prorenin are between 5 and 10 times higher than those of renin.[2] There is evidence to suggest that, in diabetes mellitus, prorenin levels are even higher.[2][7][8] One study using relatively newer technology found that blood concentrations levels may be several order of magnitude higher than previously believed, and placing it at micrograms rather than nanograms per millilitre.[9]

Pregnancy

Prorenin occurs in very high concentrations in amniotic fluid and amnion.[3] It is secreted in large amounts from the placenta and womb, and from the ovaries.[10]

Conversion to renin

Proprotein convertase 1 converts prorenin into renin,[11] but proprotein convertase 2 does not.[12]

There is no evidence that prorenin can be converted into renin in the circulation. Therefore, the granular (JG) cells seem to be the only source of active renin.[13]

References
  1. "Renin | Definition of Renin by Lexico". Lexico Dictionaries | English. Archived from the original on November 9, 2019.
  2. Jan Danser, A.H. (May 2006). "Prorenin: Back Into the Arena". Hypertension. 47 (5): 824–826. doi:10.1161/01.HYP.0000215952.91959.4a. PMID 16585418.
  3. Pringle, Kirsty G.; Wang, Yu; Lumbers, Eugenie R. (April 2015). "The synthesis, secretion and uptake of prorenin in human amnion". Physiological Reports. 3 (4): e12313. doi:10.14814/phy2.12313. PMC 4425950. PMID 25902786.
  4. Morrison, Janna L.; Lumbers, Eugenie; Bennet, Laura; Black, Jane (November 2013). "Introduction: Celebrating Emeritus Scientia Professor Eugenie R Lumbers AM and Professor Caroline McMillen". Clinical and Experimental Pharmacology and Physiology. 40 (11): 740–742. doi:10.1111/1440-1681.12180. PMID 24117727. S2CID 44555887.
  5. Lumbers, ER (30 June 1971). "Activation of renin in human amniotic fluid by low pH". Enzymologia. 40 (6): 329–336. PMID 4105386.
  6. Danser, A. H. Jan; Batenburg, Wendy W.; van Esch, Joep H. M.; Krop, Manne (June 2008). "Prorenin anno 2008". Journal of Molecular Medicine. 86 (6): 655–658. doi:10.1007/s00109-008-0318-2. PMC 2374880. PMID 18322669.
  7. Morganti, Alberto (2019). "Renin and Prorenin". Encyclopedia of Endocrine Diseases. pp. 478–482. doi:10.1016/B978-0-12-801238-3.03982-9. ISBN 978-0-12-812200-6.
  8. Jan Danser, A. H.; Batenburg, W. W.; van Esch, J. H. M. (8 March 2007). "Prorenin and the (pro)renin receptor--an update". Nephrology Dialysis Transplantation. 22 (5): 1288–1292. doi:10.1093/ndt/gfl846. PMID 17259648.
  9. Fujimoto, Kazumi; Kawamura, Sayuki; Bando, Satoru; Kamata, Yuji; Kodera, Yoshio; Shichiri, Masayoshi (June 2021). "Circulating prorenin: its molecular forms and plasma concentrations". Hypertension Research. 44 (6): 674–684. doi:10.1038/s41440-020-00610-0. PMID 33564180. S2CID 231859379.
  10. Wiegel, Rosalieke E.; von Versen-Höynck, Frauke; Steegers-Theunissen, Régine P.M.; Steegers, Eric A.P.; Danser, A.H. Jan (February 2021). "Prorenin periconceptionally and in pregnancy: Does it have a physiological role?". Molecular and Cellular Endocrinology. 522: 111118. doi:10.1016/j.mce.2020.111118. PMID 33340569. S2CID 229294165.
  11. "EC 3.4.21.93". www.qmul.ac.uk.
  12. "EC 3.4.21.94". www.qmul.ac.uk.
  13. Lote, Christopher J. (2012). "Regulation of Body Fluid Volume". Principles of Renal Physiology. pp. 105–119. doi:10.1007/978-1-4614-3785-7_9. ISBN 978-1-4614-3784-0.
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