title: Comparison of the Effects of Dibutyl and Monobutyl Phthalates on the Steroidogenesis of Rat Immature Leydig Cells.
abstract: Dibutyl phthalate (DBP) is a widely used synthetic phthalic diester and monobutyl phthalate (MBP) is its main metabolite. DBP can be released into the environment and potentially disrupting mammalian male reproductive endocrine system. However, the potencies of DBP and MBP to inhibit Leydig cell steroidogenesis and their possible mechanisms are not clear. Immature Leydig cells isolated from rats were cultured with 0.05-50 μM DBP or MBP for 3 h in combination with testosterone synthesis regulator or intermediate. The concentrations of 5α-androstanediol and testosterone in the media were measured, and the mRNA levels of the androgen biosynthetic genes were detected by qPCR. The direct actions of DBP or MBP on CYP11A1, CYP17A1, SRD5A1, and AKR1C14 activities were measured. MBP inhibited androgen production by the immature Leydig cell at as low as 50 nM, while 50 μM was required for DBP to suppress its androgen production. MBP mainly downregulated Cyp11a1 and Hsd3b1 expression levels at 50 nM. However, 50 μM DBP downregulated Star, Hsd3b1, and Hsd17b3 expression levels and directly inhibited CYP11A1 and CYP17A1 activities. In conclusion, DBP is metabolized to more potent inhibitor MBP that downregulated the expression levels of some androgen biosynthetic enzymes.
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Linxi
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anesthiology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Anesthiology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Sicong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Anesthiology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Renai
authors.initials: R
authors.lastname: Xu
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Xiaoheng
authors.initials: X
authors.lastname: Li
authors.affiliation: Taizhou Hospital of Zhejiang Province, Taizhou 317000, China.
authors.forename: Mingcang
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Anesthiology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Qing-Quan
authors.initials: QQ
authors.lastname: Lian
authors.affiliation: Center of Scientific Research, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000728:Androgens / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000009:adverse effects*; D015536:Down-Regulation / Q000187:drug effects; D004703:Endocrine System / Q000187:drug effects* / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects*; D008297:Male; D010795:Phthalic Acids / Q000009:adverse effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012098:Reproduction / Q000187:drug effects*; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013739:Testosterone / Q000096:biosynthesis
chemical_list: D000728:Androgens; D010795:Phthalic Acids; D012333:RNA, Messenger; D013256:Steroids; D003993:Dibutyl Phthalate; D013739:Testosterone; C582555:CYP17A1 protein, rat; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C028577:monobutyl phthalate