17β-Hydroxysteroid dehydrogenase type 2 expression and enzyme activity in the human gastrointestinal tract

2001 ◽  
Vol 101 (5) ◽  
pp. 485-491 ◽  
Author(s):  
Toshikazu SANO ◽  
Gen HIRASAWA ◽  
Junji TAKEYAMA ◽  
Andrew D. DARNEL ◽  
Takashi SUZUKI ◽  
...  

The 17β-hydroxysteroid dehydrogenases (17βHSDs) play an important role in the regulation of intracellular levels of biologically active sex steroid hormones in various human tissues. To date, eight distinctive 17βHSD enzymes have been cloned and characterized in humans. Among these isoenzymes, 17βHSD type 2 (17βHSD2) catalyses the conversion of testosterone into androstenedione and/or oestradiol into oestrone in various tissues, and it has thus been suggested to be involved in the biological inactivation of these sex steroids. The human gastrointestinal tract and liver are considered as the principle sites of inactivation and metabolism of various forms of orally administered sex steroids. We therefore examined 17βHSD2 expression and activity in human adult non-pathological gastrointestinal tract in order to clarify further the biological significance of this enzyme. A total of 80 specimens (40 from males and 40 from females) of normal oesophageal, stomach, duodenal, ileal, colonic and rectal tissues were examined for immunohistochemistry. Altogether, 17 tissue specimens were used for enzyme assay, and eight for RNA analysis. 17βHSD2 activity was detected in the stomach, duodenum, ileum, colon and rectum. 17βHSD2 mRNA was most abundant in the small intestine. 17βHSD2 immunoreactivity was localized almost exclusively to the absorptive epithelium, which may be involved in the inactivation of excessive endogenous and exogenous active sex steroids. Results from the present study thus suggest that the human gastrointestinal tract is an important sex steroid metabolizing organ in humans.

2019 ◽  
Vol 484 (3) ◽  
pp. 303-306
Author(s):  
V. P. Meshalkin ◽  
Yu. A. Ivashkin ◽  
M. A. Nikitina

A methodology was proposed to develop an original computer-aided multiagent model of chemicophysiological processes in the human gastrointestinal tract (GIT) as a complex living biochemical system (LBCS), which simulates chemicophysiological processes of interaction of biologically active parts and organs of GIT in models of intelligent organoid agents. The model vividly represents chemicophysiological processes of the complex LBCS as a whole and also predicts its viability and homeostasis in cases of various physiological and biochemical external actions, internal abnormalities, and malfunctioning of GIT organs.


2019 ◽  
Vol 241 (2) ◽  
pp. 111-123 ◽  
Author(s):  
Anne M Houbrechts ◽  
Jolien Van houcke ◽  
Veerle M Darras

Thyroid hormones are crucial mediators of many aspects of vertebrate life, including reproduction. The key player is the biologically active 3,5,3’-triiodothyronine (T3), whose local bio-availability is strictly regulated by deiodinase enzymes. Deiodinase type 2 (Dio2) is present in many tissues and is the main enzyme for local T3 production. To unravel its role in different physiological processes, we generated a mutant zebrafish line, completely lacking Dio2 activity. Here we focus on the reproductive phenotype studied at the level of offspring production, gametogenesis, functioning of the hypothalamic–pituitary–gonadal axis and sex steroid production. Homozygous Dio2-deficient zebrafish were hypothyroid, displayed a delay in sexual maturity and the duration of their reproductive period was substantially shortened. Fecundity and fertilization were also severely reduced. Gamete counts pointed to a delay in oogenesis at onset of sexual maturity and later on to an accumulation of oocytes in mutant ovaries due to inhibition of ovulation. Analysis of spermatogenesis showed a strongly decreased number of spermatogonia A at onset of sexual maturity. Investigation of the hypothalamic–pituitary–gonadal axis revealed that dysregulation was largely confined to the gonads with significant upregulation of igf3, and a strong decrease in sex steroid production concomitant with alterations in gene expression in steroidogenesis/steroid signaling pathways. Rescue of the phenotype by T3 supplementation starting at 4 weeks resulted in normalization of reproductive activity in both sexes. The combined results show that reproductive function in mutants is severely hampered in both sexes, thereby linking the loss of Dio2 activity and the resulting hypothyroidism to reproductive dysfunction.


2001 ◽  
Vol 101 (5) ◽  
pp. 485 ◽  
Author(s):  
Toshikazu SANO ◽  
Gen HIRASAWA ◽  
Junji TAKEYAMA ◽  
Andrew D. DARNEL ◽  
Takashi SUZUKI ◽  
...  

2007 ◽  
Vol 404 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Wera Teubner ◽  
Walter Meinl ◽  
Simone Florian ◽  
Michael Kretzschmar ◽  
Hansruedi Glatt

Soluble SULTs (sulfotransferases) are important in the regulation of messenger molecules and the elimination of xenobiotics. However, sulfo-conjugation of various substrates can also lead to the formation of reactive metabolites that may induce cancer and cause other damage. The aim of the present study was to identify the SULT forms expressed in the human gastrointestinal tract, especially the colon and rectum (common sites for cancer), and to determine their cellular localization. Normal colonic or rectal tissue, resected with tumours, was obtained from 39 subjects. For comparison, we additionally studied one to four samples from stomach, jejunum, ileum, cecum and liver. SULTs were detected by immunoblotting, immunohistochemistry and measurement of enzyme activities. SULT1A1, 1A3 and 1B1 were found in all parts of the gastrointestinal tract, often exceeding levels in liver (where these forms were present at high, undetectable and low levels respectively). They were predominantly localized in differentiated enterocytes. SULT1E1 and 2A1 were only detected in liver, jejunum, ileum and cecum. SULT1C1 was readily found in stomach, but was negligible elsewhere. SULT1A2 was present at low levels in individual samples. The remaining forms were not detected with the limitation that only high levels could be recognized with the antisera used. In conclusion, SULTs are abundant in the gastrointestinal tract of man. We suspect that they are involved in the presystemic elimination of bioactive food-borne components, including aglycones released by gut microbiota, as well as the bioactivation of some procarcinogens.


1962 ◽  
Vol 42 (3) ◽  
pp. 281-284 ◽  
Author(s):  
Wayne E. Quinton ◽  
Arnold L. Flick ◽  
Cyrus E. Rubin

Author(s):  
Erwin G. Zoetendal ◽  
Antoon D. L. Akkermans ◽  
Wilma M. Akkermans-van Vliet ◽  
J. Arjan G. M. De Visser ◽  
Willem M. De Vos

2020 ◽  
Vol 16 ◽  
Author(s):  
Mayank Chaudhary

Background:: Renin angiotensin system (RAS) is a critical pathway involved in blood pressure regulation. Octapeptide, angiotensin II (Ang aII), is biologically active compound of RAS pathway which mediates its action by binding to either angiotensin II type 1 receptor (AT1R) or angiotensin II type 2 receptor (AT2R). Binding of Ang II to AT1R facilitates blood pressure regulation whereas AT2R is primarily involved in wound healing and tissue remodelling. Objective:: Recent studies have highlighted additional role of AT2R to counter balance detrimental effects of AT1R. Activation of angiotensin II type 2 receptor using AT2R agonist has shown effect on natriuresis and release of nitric oxide. Additionally, AT2R activation has been found to inhibit angiotensin converting enzyme (ACE) and enhance angiotensin receptor blocker (ARB) activity. These findings highlight the potential of AT2R as novel therapeutic target against hypertension. Conclusion:: The potential role of AT2R highlights the importance of exploring additional mechanisms that might be crucial for AT2R expression. Epigenetic mechanisms including DNA methylation and histone modification have been explored vastly with relation to cancer but role of such mechanisms on expression of AT2R has recently gained interest.


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