Phase II metabolism, usually known as conjugation reactions, generate metabolites that are, in most cases, biologically inactive and subsequently excreted in bile or urine. Androgenic and estrogenic sex steroids are mainly inactivated by sulfation or glucuronidation by the enzyme families sulfotransferases (SULTs) or uridine diphospho glucuronosyltransferases (UGTs). This reaction step has been suggested to play an important role in regulating the intracellular levels of unconjugated steroids and their biological activity in tissues.
Variation in expression and activity in these sex-steroid conjugating enzymes have been implicated to
• play a role in numerous hormone dependent diseases, such as several types of cancer, PCOS, metabolic syndrome and osteoporosis
• impact therapeutic response to hormone related drugs including drug abuse (such as anabolic androgenic steroids)
• distort the analysis results of certain drug tests
The inter-individual variation is to a large extent due to genetic polymorphisms that changes the expression or activity of the enzyme. Other important factors are environment and diet that may have a direct impact and/or will affect the epigenome, i.e. the transcription of these genes. In addition variation between males and females has been shown in activity and mRNA expression for some of these enzymes.
The aim of this research topic forum is to highlight the progress made in this field via review papers and original articles as well as to promote future research with the aim to further understand the consequences of inter-individual difference in phase II metabolism and regulation of sex steroids.
Phase II metabolism, usually known as conjugation reactions, generate metabolites that are, in most cases, biologically inactive and subsequently excreted in bile or urine. Androgenic and estrogenic sex steroids are mainly inactivated by sulfation or glucuronidation by the enzyme families sulfotransferases (SULTs) or uridine diphospho glucuronosyltransferases (UGTs). This reaction step has been suggested to play an important role in regulating the intracellular levels of unconjugated steroids and their biological activity in tissues.
Variation in expression and activity in these sex-steroid conjugating enzymes have been implicated to
• play a role in numerous hormone dependent diseases, such as several types of cancer, PCOS, metabolic syndrome and osteoporosis
• impact therapeutic response to hormone related drugs including drug abuse (such as anabolic androgenic steroids)
• distort the analysis results of certain drug tests
The inter-individual variation is to a large extent due to genetic polymorphisms that changes the expression or activity of the enzyme. Other important factors are environment and diet that may have a direct impact and/or will affect the epigenome, i.e. the transcription of these genes. In addition variation between males and females has been shown in activity and mRNA expression for some of these enzymes.
The aim of this research topic forum is to highlight the progress made in this field via review papers and original articles as well as to promote future research with the aim to further understand the consequences of inter-individual difference in phase II metabolism and regulation of sex steroids.
