Transporter for sulfated steroid hormones in the testis − expression pattern, biological significance and implications for fertility in men and rodents

•Review on transport systems for sulfated steroids in testes of humans and animals.•Sulfated steroids are not only metabolites but can be recycled in sulfatase pathway.•A functional sulfatase pathway in the testis requires distinct transport systems.•Highlights the biological significance of the sul...

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Veröffentlicht in:The Journal of steroid biochemistry and molecular biology 2018-05, Vol.179, p.8-19
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container_title The Journal of steroid biochemistry and molecular biology
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description •Review on transport systems for sulfated steroids in testes of humans and animals.•Sulfated steroids are not only metabolites but can be recycled in sulfatase pathway.•A functional sulfatase pathway in the testis requires distinct transport systems.•Highlights the biological significance of the sulfatase pathway for fertility. In various tissues, steroid hormones may be sulfated, glucuronidated or otherwise modified. For a long time, these hydrophilic molecules have been considered to be merely inactive metabolites for excretion via bile or urine. Nevertheless, different organs such as the placenta and breast tissue produce large amounts of sulfated steroids. After the discovery of the enzyme steroid sulfatase, which is able to re-activate sulfated steroids, these precursor molecules entered the focus of interest again as a local supply for steroid hormone synthesis with a prolonged half-life compared to their unconjugated counterparts. The first descriptions of this so-called sulfatase pathway in the placenta and breast tissue (with special regards to hormone-dependent breast cancer) were quickly followed by studies of steroid sulfate production and function in the testis. These hydrophilic molecules may not permeate the cell membrane by diffusion in the way that unbound steroids can, but need to be transported through the plasma membrane by transport systems. In the testis, a functional sulfatase pathway requires the expression of specific uptake carrier and efflux transporters in testicular cells, i.e. Sertoli, Leydig and germ cells. Main focus has to be placed on Sertoli cells, as these cells build up the blood-testis barrier. In this review, an overview of carrier expression pattern in the human as well as rodent testis is provided with special interest towards implications on fertility.
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In various tissues, steroid hormones may be sulfated, glucuronidated or otherwise modified. For a long time, these hydrophilic molecules have been considered to be merely inactive metabolites for excretion via bile or urine. Nevertheless, different organs such as the placenta and breast tissue produce large amounts of sulfated steroids. After the discovery of the enzyme steroid sulfatase, which is able to re-activate sulfated steroids, these precursor molecules entered the focus of interest again as a local supply for steroid hormone synthesis with a prolonged half-life compared to their unconjugated counterparts. The first descriptions of this so-called sulfatase pathway in the placenta and breast tissue (with special regards to hormone-dependent breast cancer) were quickly followed by studies of steroid sulfate production and function in the testis. These hydrophilic molecules may not permeate the cell membrane by diffusion in the way that unbound steroids can, but need to be transported through the plasma membrane by transport systems. In the testis, a functional sulfatase pathway requires the expression of specific uptake carrier and efflux transporters in testicular cells, i.e. Sertoli, Leydig and germ cells. Main focus has to be placed on Sertoli cells, as these cells build up the blood-testis barrier. 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In various tissues, steroid hormones may be sulfated, glucuronidated or otherwise modified. For a long time, these hydrophilic molecules have been considered to be merely inactive metabolites for excretion via bile or urine. Nevertheless, different organs such as the placenta and breast tissue produce large amounts of sulfated steroids. After the discovery of the enzyme steroid sulfatase, which is able to re-activate sulfated steroids, these precursor molecules entered the focus of interest again as a local supply for steroid hormone synthesis with a prolonged half-life compared to their unconjugated counterparts. The first descriptions of this so-called sulfatase pathway in the placenta and breast tissue (with special regards to hormone-dependent breast cancer) were quickly followed by studies of steroid sulfate production and function in the testis. These hydrophilic molecules may not permeate the cell membrane by diffusion in the way that unbound steroids can, but need to be transported through the plasma membrane by transport systems. In the testis, a functional sulfatase pathway requires the expression of specific uptake carrier and efflux transporters in testicular cells, i.e. Sertoli, Leydig and germ cells. Main focus has to be placed on Sertoli cells, as these cells build up the blood-testis barrier. 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subjects Bile
Breast cancer
Excretion
Fertility
Germ cells
Metabolites
Placenta
Reproductive system
Sertoli cells
Steroid hormones
Steroid sulfatase
Steroids
Sulfatase pathway
Sulfated steroid hormones
Sulfates
Testicular cancer
Testicular target cells
Tissues
Uptake and efflux transporters
Urine
title Transporter for sulfated steroid hormones in the testis − expression pattern, biological significance and implications for fertility in men and rodents
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