Biosynthesis and release of pheromonal bile salts in mature male sea lamprey

Cory O. Brant1, Yu Wen Chung-Davidson1, Ké Li1, Anne M. Scott1, Weiming Li1
1Department of Fisheries and Wildlife, Michigan State University, Room 13 Natural Resources Building, 480 Wilson Road, 48824, East Lansing, MI, USA

Tóm tắt

Abstract Background In vertebrates, bile salts are primarily synthesized in the liver and secreted into the intestine where they aid in absorption of dietary fats. Small amounts of bile salts that are not reabsorbed into enterohepatic circulation are excreted with waste. In sexually mature male sea lamprey (Petromyzon marinus L.) a bile salt is released in large amounts across gill epithelia into water where it functions as a pheromone. We postulate that the release of this pheromone is associated with a dramatic increase in its biosynthesis and transport to the gills upon sexual maturation. Results We show an 8000-fold increase in transcription of cyp7a1, a three-fold increase in transcription of cyp27a1, and a six-fold increase in transcription of cyp8b1 in the liver of mature male sea lamprey over immature male adults. LC–MS/MS data on tissue-specific distribution and release rates of bile salts from mature males show a high concentration of petromyzonol sulfate (PZS) in the liver and gills of mature males. 3-keto petromyzonol sulfate (3kPZS, known as a male sex pheromone) is the primary compound released from gills, suggesting a conversion of PZS to 3kPZS in the gill epithelium. The PZS to 3kPZS conversion is supported by greater expression of hsd3b7 in gill epithelium. High expression of sult2b1 and sult2a1 in gill epithelia of mature males, and tissue-specific expression of bile salt transporters such as bsep, slc10a1, and slc10a2, suggest additional sulfation and transport of bile salts that are dependent upon maturation state. Conclusions This report presents a rare example where specific genes associated with biosynthesis and release of a sexual pheromone are dramatically upregulated upon sexual maturation in a vertebrate. We provide a well characterized example of a complex mechanism of bile salt biosynthesis and excretion that has likely evolved for an additional function of bile salts as a mating pheromone.

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Tài liệu tham khảo

Elliott WH, Hyde PM: Metabolic pathways of bile acid synthesis. Am J Med. 1971, 51 (5): 568-579. 10.1016/0002-9343(71)90281-6.

Russell DW, Setchell KDR: Bile-acid biosynthesis. Biochemistry. 1992, 31 (20): 4737-4749. 10.1021/bi00135a001.

Hofmann AF, Hagey LR: Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics. Cell Mol Life Sci. 2008, 65 (16): 2461-2483. 10.1007/s00018-008-7568-6.

Wang RX, Sheps JA, Ling V: ABC transporters, bile acids, and inflammatory stress in liver cancer. Curr Pharm Biotechnol. 2011, 12 (4): 636-646. 10.2174/138920111795163986.

Li W, Scott AP, Siefkes MJ, Yan HG, Liu Q, Yun SS, Gage DA: Bile acid secreted by mate sea lamprey that acts as a sex pheromone. Science. 2002, 296 (5565): 138-141. 10.1126/science.1067797.

Johnson NS, Yun SS, Thompson HT, Brant CO, Li WM: A synthesized pheromone induces upstream movement in female sea lamprey and summons them into traps. Proc Natl Acad Sci USA. 2009, 106 (4): 1021-1026. 10.1073/pnas.0808530106.

Yeh CY, Chung-Davidson YW, Wang HY, Li K, Li WM: Intestinal synthesis and secretion of bile salts as an adaptation to developmental biliary atresia in the sea lamprey. Proc Natl Acad Sci USA. 2012, 109 (28): 11419-11424. 10.1073/pnas.1203008109.

Applegate VC: Natural history of the sea lamprey (Petromyzon marinus) in Michigan. 1950, Washington D. C: United States Department of the Interior Fish and Wildlife Service

Siefkes MJ, Scott AP, Zielinski B, Yun SS, Li W: Male sea lampreys, Petromyzon marinus L., excrete a sex pheromone from gill epithelia. Biol Reprod. 2003, 69 (1): 125-132. 10.1095/biolreprod.102.014472.

Yun SS, Scott AP, Li W: Pheromones of the male sea lamprey, Petromyzon marinus L.: structural studies on a new compound, 3-keto allocholic acid, and 3-keto petromyzonol sulfate. Steroids. 2003, 68 (3): 297-304. 10.1016/S0039-128X(02)00178-2.

Li K, Siefkes MJ, Brant CO, Li W: Isolation and identification of petromyzestrosterol, a polyhydroxysteroid from sexually mature male sea lamprey (Petromyzon marinus L.). Steroids. 2012, 77 (7): 806-810. 10.1016/j.steroids.2012.03.006.

Siefkes MJ, Winterstein SR, Li W: Evidence that 3-keto petromyzonol sulphate specifically attracts ovulating female sea lamprey, Petromyzon marinus. Anim Behav. 2005, 70: 1037-1045. 10.1016/j.anbehav.2005.01.024.

Haselwood GAD, Tökés L: Comparative studies of bile salts. Biochem J. 1969, 114: 179-184.

Li WM, Sorensen PW, Gallaher DD: The olfactory system of migratory adult sea lamprey (Petromyzon marinus) is specifically and acutely sensitive to unique bile-acids released by conspecific larvae. J Gen Physiol. 1995, 105 (5): 569-587. 10.1085/jgp.105.5.569.

Sorensen PW, Fine JM, Dvornikovs V, Jeffrey CS, Shao F, Wang JZ, Vrieze LA, Anderson KR, Hoye TR: Mixture of new sulfated steroids functions as a migratory pheromone in the sea lamprey. Nat Chem Biol. 2005, 1 (6): 324-328. 10.1038/nchembio739.

Siefkes MJ, Li W: Electrophysiological evidence for detection and discrimination of pheromonal bile acids by the olfactory epithelium of female sea lampreys (Petromyzon marinus). J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2004, 190 (3): 193-199. 10.1007/s00359-003-0484-1.

Johnson NS, Yun SS, Buchinger TJ, Li W: Multiple functions of a multi-component mating pheromone in sea lamprey Petromyzon marinus. J Fish Biol. 2012, 80 (3): 538-554. 10.1111/j.1095-8649.2011.03185.x.

Augustinsson KB RF, Johnels A, Ostlund E: Histological, physiological, and biochemical studies on the heart of two cyclostomes, hagfish (Myxine) and lamprey (Lampetra). J Physiol. 1956, 131: 257-276.

Polkinghorne CN, Olson JM, Gallaher DG, Sorensen PW: Larval sea lamprey release two unique bile acids to the water at a rate sufficient to produce detectable riverine pheromone plumes. Fish Physiol Biochem. 2001, 24 (1): 15-30. 10.1023/A:1011159313239.

Wagner CM, Twohey MB, Fine JM: Conspecific cueing in the sea lamprey: do reproductive migrations consistently follow the most intense larval odour?. Anim Behav. 2009, 78 (3): 593-599. 10.1016/j.anbehav.2009.04.027.

Meckley TD, Wagner CM, Luehring MA: Field evaluation of larval odor and mixtures of synthetic pheromone components for attracting migrating sea lampreys in rivers. J Chem Ecol. 2012, 38 (8): 1062-1069. 10.1007/s10886-012-0159-x. Published online: 14 July 2012

Venkatachalam KV: Petromyzonol sulfate and its derivatives: the chemoattractants of the sea lamprey. Bioessays. 2005, 27 (2): 222-228. 10.1002/bies.20155.

Gamage N, Barnett A, Hempel N, Duggleby RG, Windmill KF, Martin JL, McManus ME: Human sulfotransferases and their role in chemical metabolism. Toxicol Sci. 2006, 90 (1): 5-22.

Sidon EW, Youson JH: Morphological changes in the liver of the sea lamprey, Petromyzon marinus L., during metamorphosis. II. Canalicular degeneration and transformation of the hepatocytes. J Morphol. 1983, 178: 225-246. 10.1002/jmor.1051780303.

Stieger B, Meier Y, Meier PJ: The bile salt export pump. Pflugers Arch. 2007, 453 (5): 611-620. 10.1007/s00424-006-0152-8.

Trauner M, Boyer JL: Bile salt transporters: molecular characterization, function, and regulation. Physiol Rev. 2003, 83 (2): 633-671.

Lionarons DA, Boyer JL, Cai SY: Evolution of substrate specificity for the bile salt transporter ASBT (SLC10A2). J Lipid Res. 2012, 53 (8): 1535-1542. 10.1194/jlr.M025726.

Hagey LR, Møller PR, Hofmann AF, Krasowski MD: Diversity of bile salts in fish and amphibians: Evolution of a complex biochemical pathway. Physiol Biochem Zool. 2010, 83 (2): 308-321.

Manion PJ, Hanson LH: Spawning behavior and fecundity of lampreys from the upper three Great Lakes. Can J Fish Aquat Sci. 1980, 37 (11): 1635-1640. 10.1139/f80-211.

Li K, Wang HY, Brant CO, Ahn S, Li W: Multiplex quantification of lamprey specific bile acid derivatives in environmental water using UHPLC-MS/MS. J Chromatogr B. 2011, 879 (32): 3879-3886. 10.1016/j.jchromb.2011.10.039.

Scherer M, Gnewuch C, Schmitz G, Liebisch G: Rapid quantification of bile acids and their conjugates in serum by liquid chromatography-tandem mass spectrometry. J Chromatogr B. 2009, 877 (30): 3920-3925. 10.1016/j.jchromb.2009.09.038.

Chung-Davidson YW, Rees CB, Bryan MB, Li W: Neurogenic and neuroendocrine effects of goldfish pheromones. J Neurosci. 2008, 28 (53): 14492-14499. 10.1523/JNEUROSCI.3589-08.2008.