Cantharidin and norcantharidin inhibit caprine luteal cell steroidogenesis in vitro.
Cantharidin and its analog norcantharidin are active constituents of Mylabris, have been demonstrated to ailments for a variety of cancers. But several reports of cantharidin's natural or accidental toxicoses in field animals and humans showed a strong connection between cantharidin and its abortifacient and aphrodisiac properties. However, their exact cellular mechanisms in steroidogenesis remains poorly understood. Thus this study was aimed to explore the effects of cantharidin on luteal cell steroidogensis and to compare its effect with that of norcantharidin. For this purpose, luteal cells isolated from corpora lutea of native Taiwan goats were maintained in vitro and treated for 4 and 24 h with cantharidin and norcantharidin (0.1, 1.0, and 10 μg ml(-1)) to assess their steroidogenic effects. Progesterone (P(4)) levels and steroidogenic enzyme expression were assessed by enzyme immunoassay and Western blot methods, respectively. In caprine luteal cells, cantharidin and norcantharidin repressed basal P(4) production, as well as that mediated by ovine luteinizing hormone (oLH), 8-bromo-cyclic AMP (8-Br-cAMP), 22R-hydroxycholesterol (22R-OHC) and pregnenolone (P(5)). They also inhibited the expression of steroidogenic acute regulatory (StAR) protein, cytochrome P450 cholesterol side-chain cleavage (P450scc) enzyme, and 3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme. Additionally, the greater inhibitory effect was detected using cantharidin, when it is compared with that of norcantharidin. Our results suggest that ingestion of cantharidin may decrease luteal steroidogenesis, and the decline in luteal P(4) levels may disrupt reproductive functions in humans as well as animals.
Twu
Nae-Fang
NF
Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, National Yang-Ming University, Taiwan.
Srinivasan
Ramanujam
R
Chou
Chung-Hsi
CH
Wu
Leang-Shin
LS
Chiu
Chih-Hsien
CH
D015096:3-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis; D000818:Animals; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000633:toxicity*; D002193:Cantharidin / Q000633:toxicity*; D018929:Cell Culture Techniques; D002460:Cell Line; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D006041:Goats; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis; D011374:Progesterone / Q000096:biosynthesis* / Q000378:metabolism; D000098682:Steroidogenic Acute Regulatory Protein
D019086:Bridged Bicyclo Compounds, Heterocyclic; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; C069741:norcantharidin; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D002193:Cantharidin