PMID- 17479410
OWN - NLM
STAT- MEDLINE
DCOM- 20070517
LR  - 20171116
IS  - 1528-7394 (Print)
IS  - 0098-4108 (Linking)
VI  - 70
IP  - 11
DP  - 2007 Jun
TI  - Monobutyl phthalate inhibits steroidogenesis by downregulating steroidogenic 
      acute regulatory protein expression in mouse Leydig tumor cells (MLTC-1).
PG  - 947-55
AB  - Di-n-butyl phthalate (DBP) and its active metabolite, monobutyl phthalate (MBP), 
      display no binding affinity for the androgen receptor, yet exert antiandrogenic 
      effects by altering steroid biosynthesis. However, the mechanisms underlying this 
      observed effect are not known. The purpose of this study was to determine the 
      site of MBP action on steroidogenesis in vitro using mouse Leydig tumor cells 
      (MLTC-1). Various concentrations of MBP (0, 50, 100, 200, 400, or 800 micromol/L) 
      were added to the medium for 24 h followed by stimulation with some compounds 
      such as human chorionic gonadotrophin (hCG), cholera toxin (CT), cAMP analog 
      8-Br-cAMP, 22(R)-hydroxycholesterol (22R-HC), and pregnenolone. Data showed that 
      MBP inhibited the increases in progesterone production induced by hCG and CT. In 
      contrast, the levels of intracellular cAMP remained unaltered. In addition, 
      8-Br-cAMP-stimulated progesterone production was also suppressed by MBP. These 
      results suggested that the site in the steroid biosynthesis pathway affected by 
      MBP occurs downstream of PKA activation in MLTC-1 cells. Moreover, incubation 
      with 22R-HC and pregnenolone as progesterone precursors for P-450 side-chain 
      cleavage enzyme (P450scc) and 3beta-hydroxysteroid dehydrogenase (3betaHSD) 
      respectively resulted in no marked change in progesterone production, indicating 
      that MBP did not influence P450scc and 3betaHSD but did exert an effect on 
      cholesterol transportation into mitochondria, the rate-limiting step. These 
      results were supported by the downregulated StAR expression seen with MBP 
      administration, as StAR is a key factor in this process. Data indicate that MBP 
      interfered with steroid hormone production by affecting StAR expression in MLTC-1 
      cells.
FAU - Wang, Yu-Bang
AU  - Wang YB
AD  - Key Laboratory of Reproductive Medicine of Jiangsu Province, Institute of 
      Toxicology, Nanjing Medical University, Nanjing, People's Republic of China.
FAU - Song, Ling
AU  - Song L
FAU - Cui, Lun-Biao
AU  - Cui LB
FAU - Hong, Xia
AU  - Hong X
FAU - Zhang, Zheng-Dong
AU  - Zhang ZD
FAU - Wang, Xin-Ru
AU  - Wang XR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Toxicol Environ Health A
JT  - Journal of toxicology and environmental health. Part A
JID - 100960995
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (Drug Combinations)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Hydroxycholesterols)
RN  - 0 (Phosphoproteins)
RN  - 0 (Phthalic Acids)
RN  - 0 (RNA, Messenger)
RN  - 0 (steroidogenic acute regulatory protein)
RN  - 17711-16-9 (22-hydroxycholesterol)
RN  - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 73R90F7MQ8 (Pregnenolone)
RN  - 9012-63-9 (Cholera Toxin)
RN  - E0399OZS9N (Cyclic AMP)
RN  - ZI46LWZ45G (monobutyl phthalate)
SB  - IM
MH  - 8-Bromo Cyclic Adenosine Monophosphate/pharmacology
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Cholera Toxin/pharmacology
MH  - Chorionic Gonadotropin/pharmacology
MH  - Cyclic AMP/metabolism
MH  - DNA Replication/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/drug effects
MH  - Drug Combinations
MH  - Endocrine Disruptors/*toxicity
MH  - Humans
MH  - Hydroxycholesterols/pharmacology
MH  - Leydig Cell Tumor/*drug therapy/metabolism
MH  - Male
MH  - Mice
MH  - Mitochondria/drug effects/metabolism
MH  - Phosphoproteins/genetics/*metabolism
MH  - Phthalic Acids/*toxicity
MH  - Pregnenolone/pharmacology
MH  - Progesterone/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Testicular Neoplasms/*drug therapy/metabolism
EDAT- 2007/05/05 09:00
MHDA- 2007/05/18 09:00
CRDT- 2007/05/05 09:00
PHST- 2007/05/05 09:00 [pubmed]
PHST- 2007/05/18 09:00 [medline]
PHST- 2007/05/05 09:00 [entrez]
AID - 778156631 [pii]
AID - 10.1080/15287390701290717 [doi]
PST - ppublish
SO  - J Toxicol Environ Health A. 2007 Jun;70(11):947-55. doi: 
      10.1080/15287390701290717.