Biotransformation of dihydroisosteviol and the effects of transformed products on steroidogenic gene expressions.
The biotransformation of dihydroisosteviol with Absidia pseudocylindrospora ATCC 24169, Streptomyces griseus ATCC 10137, Mucor recurvatus MR36, and Aspergillus niger BCRC 31130 yielded 15 metabolites, eight of which were previously unknown. Structures of metabolites were established by 2D NMR techniques and HRMS data, two of which were further corroborated by chemical means, and another via single-crystal X-ray diffraction analysis. Subsequently, two steroidogenic cell lines (Y-1 mouse adrenal tumor and MA-10 mouse Leydig tumor cells) were used in a reverse transcription-PCR analysis to assess the effects of all compounds on steroidogenic gene expressions using forskolin as a positive control. The tested gene expressions included steroidogenic factor-1 (SF-1), steroidogenic acute regulatory protein (StAR), and cytochrome P450 side-chain cleavage (P450scc) enzyme. Gene expression profiles showed that ten of the tested compounds effectively suppressed P450SCC mRNA expression in both Y-1 and MA-10 cells. Several induced SF-1 gene expression and two enhanced StAR gene expression in Y-1 cells. By contrast, in MA-10 cells, one compound effectively suppressed StAR mRNA expression, whereas for others effectively suppressed SF-1 gene expression. The results suggest that analogs of dihydroisosteviol can be potential modulators to alter steroidogenic gene expressions and subsequent enzyme activities.
Division of Cell and Molecular Biology, Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Shwu-Fen
SF
Chang
Li-Ming
LM
Yang
Tsurng-Juhn
TJ
Huang
Chin-Yang
CY
Chen
Shiow-Yunn
SY
Sheu
Pan-Chun
PC
Liu
Shwu-Jiuan
SJ
Lin
D000818:Animals; D001419:Bacteria; D001711:Biotransformation; D045744:Cell Line, Tumor; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005658:Fungi; D015870:Gene Expression / Q000187:drug effects*; D051379:Mice; D015394:Molecular Structure; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*; D036625:Stevia / Q000737:chemistry*; D000098682:Steroidogenic Acute Regulatory Protein
D045786:Diterpenes, Kaurane; D010750:Phosphoproteins; D012333:RNA, Messenger; D054339:Steroidogenic Factor 1; C583718:dihydroisosteviol; D000098682:Steroidogenic Acute Regulatory Protein; D005576:Colforsin; D002786:Cholesterol Side-Chain Cleavage Enzyme
Biotransformation; Dihydroisosteviol; Steroidogenic genes