title: Swainsonine differentially affects steroidogenesis and viability in caprine luteal cells in vitro.
abstract: Plants containing swainsonine (SW) have been reported to impair reproductive function and fertility after long-term ingestion by livestock. However, direct effects of SW on luteal cell steroidogenesis remain unclear. In this study, primary and transfected luteal cells were used to investigate the effects of SW on progesterone secretion and cell viability and the mechanisms involved in these processes. After treatment with various concentrations of SW for 24 or 48 hours, progesterone production and the number of living cells were assessed using radioimmunoassay and trypan blue dye exclusion assay, respectively. Lower concentrations of SW enhanced basal, 22R-hydroxycholesterol- or pregnenolone-stimulated progesterone secretion (P < 0.05), whereas higher concentrations of SW inhibited progesterone secretion (P < 0.05). Lower concentrations of SW promoted expression of P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase, two key enzymes involved in luteal cell steroidogenesis, at mRNA and protein levels (P < 0.05), but did not affect expression of steroidogenic acute regulatory protein and cell proliferation. In contrast, higher concentrations of SW inhibited luteal cell proliferation by inducing growth phase 1/quiescent state cell cycle arrest and apoptosis (P < 0.05). Taken together, these results demonstrated that lower concentrations of SW induced progesterone production through upregulation of P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase without affecting cell viability, whereas higher concentrations of SW induced cell cycle arrest and apoptosis and impaired steroidogenesis. These findings provided new insights into understanding the effect of SW on luteal cell steroidogenesis.
authors: College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi, China.
authors: Yong
authors: Y
authors: Huang
authors: Wei
authors: W
authors: Li
authors: Xiaomin
authors: X
authors: Zhao
authors: Li
authors: L
authors: Ding
authors: Gaoshui
authors: G
authors: Yu
authors: Feng
authors: F
authors: Dong
authors: Qian
authors: Q
authors: Du
authors: Xingang
authors: X
authors: Xu
authors: Dewen
authors: D
authors: Tong
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000032:analysis / Q000235:genetics; D003470:Culture Media; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006041:Goats; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism*; D033021:Oxytropis / Q000737:chemistry; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics; D011247:Pregnancy; D011284:Pregnenolone / Q000494:pharmacology; D011374:Progesterone / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D017026:Swainsonine / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D014162:Transfection; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D003470:Culture Media; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D011284:Pregnenolone; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017026:Swainsonine