HGNC Approved Gene Symbol: SCT
Cytogenetic location: 11p15.5 Genomic coordinates (GRCh38): 11:626,309-627,181 (from NCBI)
The SCT gene encodes secretin, a small hormone produced by specific endocrine cells, S cells, located in the mucosa of the proximal small intestine. Since its discovery by Bayliss and Starling (1902), secretin has been known to be a potent stimulus for the secretion of bicarbonate-rich pancreatic juice. Secretion of secretin is stimulated by the presence of either acidic pH or fatty acids in the duodenum (summary by Kopin et al., 1990).
The amino acid sequence of secretin was determined by Mutt et al. (1970). Secretin is a 27-amino acid peptide and is synthesized as a larger precursor.
Kopin et al. (1990) isolated cDNAs encoding the rat and porcine secretin precursors. The deduced amino acid sequence included a signal peptide, an N-terminal peptide, secretin itself, and a 72-amino acid C-terminal peptide. They used secretin cDNA as a probe in Northern blot hybridizations to determine the distribution in extraintestinal tissues. Although secretin immunoreactivity in the central nervous system has been claimed by some, Kopin et al. (1990) were unable to detect secretin mRNA in the CNS by Northern blot hybridization.
By Northern blot analysis, Whitmore et al. (2000) detected strong expression of an 0.8-kb SCT transcript in spleen, testis, and small intestine. Weak expression was detected in most brain regions, with a stronger band in the medulla, and in duodenum, ileocecum, ileum, and jejunum.
Whitmore et al. (2000) isolated the SCT gene from a BAC genomic library. SCT contains 4 exons, with the protein-coding regions spanning 713 bp of genomic DNA.
By radiation hybrid analysis, Whitmore et al. (2000) mapped the SCT gene to chromosome 11p15.5.
Secretin stimulates ductal bile secretion by directly interacting with cholangiocytes. It stimulates exocytosis in cholangiocytes, which transport water mainly via the water channel aquaporin-1 (AQP1; 107776). Marinelli et al. (1997) tested the hypothesis that secretin promotes osmotic water movement in cholangiocytes by inducing the exocytic insertion of AQP1 into plasma membranes. They demonstrated that secretin increases AQP1-mediated membrane water permeability (Pf) in cholangiocytes. Moreover, they stated that their studies implicate the microtubule-dependent vesicular translocation of AQP1 water channels to the plasma membrane, a mechanism that appears to be essential for secretin-induced ductal bile secretion and suggests that AQP1 can be regulated by membrane trafficking.
Chu et al. (2007) showed that Sctr (182098)-null mice developed mild polydipsia and polyuria associated with reduced renal expression of Aqp2 (107777) and Aqp4 (600308), as well as altered glomerular and tubular morphology, suggesting possible disturbances in the filtration and/or water reabsorption. In vitro and in vivo mouse studies demonstrated a role for secretin in stimulating Aqp2 translocation from intracellular vesicles to the plasma membrane in renal medullary tubules, and expression of this water channel under hyperosmotic conditions. These findings identified a vasopressin (AVP; 192340)-independent mechanism for secretin in modulation of renal water reabsorption.
In rat brain, Chu et al. (2009) detected expression of secretin and its receptor in the hypothalamus, where they were distributed in magnocellular neurons in the supraoptic nucleus (SON) and in parvocellular and magnocellular neurons in the paraventricular nucleus (PVN). Expression was also observed in the posterior lobe of the pituitary. Intraventricular administration of SCT resulted in expression of Fos (164810) in the PVN and SON, indicating increased activity in these brain regions. Increased Fos expression was associated with induction of vasopressin gene expression and its secretion into the peripheral circulation. Sct and Sctr expression and Sct release were significantly increased in the hypothalamus and pituitary of hypovolemic mice. Chu et al. (2009) concluded that secretin is present throughout the hypothalamo-neurohypophysial axis and stimulates vasopressin expression in the hypothalamus and release from the posterior pituitary, which ultimately acts on the kidney to regulate water homeostasis. Secretin also acts as a neurosecretory factor that itself is released from the posterior pituitary under plasma hyperosmolality conditions, where it can act directly on the kidney.
Bayliss, W., Starling, E. H. The mechanism of pancreatic secretion. J. Physiol. (London) 28: 325-353, 1902.
Chu, J. Y. S., Chung, S. C. K., Lam, A. K. M., Tam, S., Chung, S. K., Chow, B. K. C. Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption. Molec. Cell Biol. 27: 2499-2511, 2007. [PubMed: 17283064] [Full Text: https://doi.org/10.1128/MCB.01088-06]
Chu, J. Y. S., Lee, L. T. O., Lai, C. H., Vaudry, H., Chan, Y. S., Yung, W. H., Chow, B. K. C. Secretin as a neurohypophysial factor regulating body water homeostasis. Proc. Nat. Acad. Sci. 106: 15961-15966, 2009. [PubMed: 19805236] [Full Text: https://doi.org/10.1073/pnas.0903695106]
Kopin, A. S., Wheeler, M. B., Leiter, A. B. Secretin: structure of the precursor and tissue distribution of the mRNA. Proc. Nat. Acad. Sci. 87: 2299-2303, 1990. [PubMed: 2315322] [Full Text: https://doi.org/10.1073/pnas.87.6.2299]
Marinelli, R. A., Pham, L., Agre, P., LaRusso, N. F. Secretin promotes osmotic water transport in rat cholangiocytes by increasing aquaporin-1 water channels in plasma membrane. J. Biol. Chem. 272: 12984-12988, 1997. [PubMed: 9148905] [Full Text: https://doi.org/10.1074/jbc.272.20.12984]
Mutt, V., Jorpes, J. E., Magnusson, S. Structure of porcine secretin: the amino acid sequence. Europ. J. Biochem. 15: 513-519, 1970. [PubMed: 5465996] [Full Text: https://doi.org/10.1111/j.1432-1033.1970.tb01034.x]
Whitmore, T. E., Holloway, J. L., Lofton-Day, C. E., Maurer, M. F., Chen, L., Quinton, T. J., Vincent, J. B., Scherer, S. W., Lok, S. Human secretin (SCT): gene structure, chromosome location, and distribution of mRNA. Cytogenet. Cell Genet. 90: 47-52, 2000. [PubMed: 11060443] [Full Text: https://doi.org/10.1159/000015658]