title: Evidence of estrone-sulfate uptake modification in young and middle-aged rat prostate.
abstract: High plasma exposure to estrogens is often associated with prostate cancer. Reducing this phenomenon may present therapeutic benefits. The involvement of estrone sulphate (E1S), the most abundant circulating estrogen in men, has been partially studied in this age-related pathology. To investigate the consequences of plasma E1S overload on blood and prostate sex steroid levels and inflammatory tissue responses, young and middle-aged male rats were treated with E1S with or without steroid sulfatase (STS) inhibitor STX64 for 21 consecutive days. A plasma and prostate tissue steroid profile was determined. STS activity, mRNA expression of E1S organic anion transporting polypeptides (slco1a2, slco2b1, slco4a1) and pro-inflammatory cytokines (Il1-beta, Il6, TNF-alpha) were evaluated in prostate tissue according to age and treatment group. A significant correlation between plasma and prostate steroid levels related to hormone treatment was observed in all rat age groups. However, while the E1S level in prostate tissue increased in middle-aged treated rats (p<0.0001), no significant variation was observed in young treated rats. The protective effect of STX64 during E1S infusion was observed by the maintenance of low free estrogen concentrations in both plasma and tissue. However, this protection was not associated with mRNA expression stability of pro-inflammatory cytokines in older rat prostate. These results suggest that E1S uptake in rat prostate cells increases during aging. Therefore, if a similar phenomenon existed in men, preventively reducing the STS activity could be of interest to limit uptake of estrogens in prostate when high E1S plasma level is assayed.
authors.affiliation: AP-HP, CIB GHU Sud Henri Mondor, Créteil 94000, France; INSERM, U955 eq07, Créteil 94000, France. Electronic address: giton@u-pec.fr.
authors.forename: Frank
authors.initials: F
authors.lastname: Giton
authors.affiliation: INSERM, U955 eq07, Créteil 94000, France.
authors.forename: Nanor
authors.initials: N
authors.lastname: Sirab
authors.affiliation: CNRS, EAC7054, Créteil 94000, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Franck
authors.affiliation: CNRS, EAC7054, Créteil 94000, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Gervais
authors.affiliation: Ipsen SCRAS IHB, Les Ulis, 91966, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Schmidlin
authors.affiliation: Ipsen, Bath Road, Slough, UK.
authors.forename: Tauhid
authors.initials: T
authors.lastname: Ali
authors.affiliation: AP-HP, CIB GHU Sud Henri Mondor, Créteil 94000, France; INSERM, U955 eq07, Créteil 94000, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.affiliation: INSERM, U955 eq07, Créteil 94000, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de la Taille
authors.affiliation: INSERM, U955 eq07, Créteil 94000, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Vacherot
authors.affiliation: AP-HP, CIB GHU Sud Henri Mondor, Créteil 94000, France; INSERM, U955 eq07, Créteil 94000, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Loric
authors.affiliation: INSERM, U955 eq07, Créteil 94000, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Fiet
mesh_terms: D000367:Age Factors; D000818:Animals; D017920:Antiporters / Q000096:biosynthesis / Q000235:genetics; D001692:Biological Transport; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004967:Estrogens / Q000097:blood* / Q000494:pharmacology; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005136:Eye Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D023421:Models, Animal; D027361:Organic Anion Transporters / Q000096:biosynthesis / Q000235:genetics; D011467:Prostate / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors*; D013451:Sulfonic Acids / Q000494:pharmacology*
chemical_list: D017920:Antiporters; D016207:Cytokines; D004967:Estrogens; D004966:Estrogens, Conjugated (USP); D005136:Eye Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C478703:Slco4a1 protein, rat; D013451:Sulfonic Acids; D004970:Estrone; C520511:irosustat; D043266:Steryl-Sulfatase; C017296:estrone sulfate
keywords: Estrogens; Estrone sulfate; Organic anion transporting polypeptides; Pro-inflammatory cytokines; Prostate cancer; Sulfatase inhibitor