On the mode of action of a new contragestational agent (DL 111-IT)

Galliani, G.; Luzzani, Franco; Colombo, Graziano; Conz, A.; Mistrello, L.; Barone, Domenico; Lancini, Giancarlo; Assandri, Alessandro

doi:10.1016/0010-7824(86)90019-3

Cited by 24 publications

(4 citation statements)

References 23 publications

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“…SAMDC was considered to be the most important polyamine synthetase after ODC [26]. Studies have found that both ODC knockout and SAMDC knockout are lethal in mouse embryos [27,28]. In this experiment, the interference or overexpression of ODC affected the gene expression of polyamine metabolism enzyme in GCs.…”

Section: Discussionmentioning

confidence: 87%

Effects of ODC on Polyamine Metabolism, Hormone Levels, Cell proliferation and Apoptosis in Goose Ovarian Granulosa Cells

Niu

Zhang

et al. 2020

Preprint

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Background: Ornithine decarboxylase (ODC) plays an indispensable role in the process of polyamine biosynthesis. Polyamines are a pivotal part of living cells and have diverse roles in the regulation of cell proliferation and apoptosis, aging and reproduction. However, to date, there have been no reports about ODC regulating follicular development in goose ovaries. Here, we constructed ODC siRNA and overexpression plasmids and transfected them into goose primary granulosa cells (GCs) to elucidate the effects of ODC interference and overexpression on the polyamine metabolism, hormone levels, cell apoptosis and proliferation of granulosa cells.Results: After interfering with ODC in GCs, the mRNA and protein levels of ODC and the content of putrescine were greatly decreased (P < 0.05). When ODC was overexpressed, ODC mRNA and protein levels and putrescine content were greatly increased (P < 0.05). The polyamine-metabolizing enzyme genes OAZ1 and SSAT were significantly increased, and SPDS was significantly decreased when ODC was downregulated (P < 0.05). OAZ1, SPDS and SSAT were significantly increased when ODC was upregulated (P < 0.05). In addition, after interference with ODC, P4 (progesterone) levels in the culture medium of GCs increased greatly (P < 0.05), while the overexpression of ODC caused the P4 level to decrease significantly (P < 0.05). After ODC downregulation, granulosa cell activity was significantly reduced, the apoptosis rate was significantly increased, and the BCL-2/BAX ratio was downregulated (P < 0.05). Under ODC overexpression, the activity of GCs was notably increased, the apoptosis rate was significantly reduced, and the BCL-2/BAX protein ratio was upregulated (P < 0.05).Conclusions: Our study successfully induced ODC interference and overexpression in goose ovarian GCs, and ODC regulated mainly putrescine content in GCs with a slight influence on spermidine and spermine. Moreover, ODC participated in the adjustment of P4 levels in the culture medium of GCs, promoted granulosa cell proliferation and inhibited granulosa cell apoptosis.

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Section: Discussionmentioning

confidence: 87%

Effects of ODC on Polyamine Metabolism, Hormone Levels, Cell proliferation and Apoptosis in Goose Ovarian Granulosa Cells

Niu

Zhang

et al. 2020

Preprint

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“…ODC activity in mammalian ovaries was reported to transiently increase as oocytes mature in vivo, and oocyte maturation and development are regulated by GCs. In the early pregnancy of hamsters and rats, treatment with progesterone receptor antagonists can result in decreased ODC activity and eventually lead to miscarriage, which indicates that ODC activity in the ovary is closely related to hormones ( Galliani et al., 1986 ; Jian et al., 2001 ). This study found that after interfering with ODC , the E2 level was remarkably reduced, and ER expression was greatly decreased.…”

Section: Discussionmentioning

confidence: 99%

Effects of ODC on polyamine metabolism, hormone levels, cell proliferation and apoptosis in goose ovarian granulosa cells

Niu

Zhang

et al. 2021

Poultry Science

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Ornithine decarboxylase ( ODC ) plays an indispensable role in the process of polyamine biosynthesis. Polyamines are a pivotal part of living cells and have diverse roles in the regulation of cell proliferation and apoptosis, aging and reproduction. However, to date, there have been no reports about ODC regulating follicular development in goose ovaries. Here, we constructed ODC siRNA and overexpression plasmids and transfected them into goose primary granulosa cells ( GCs ) to elucidate the effects of ODC interference and overexpression on the polyamine metabolism, hormone levels, cell apoptosis and proliferation of granulosa cells. After interfering with ODC in GCs, the mRNA and protein levels of ODC and the content of putrescine were greatly decreased ( P < 0.05). When ODC was overexpressed, ODC mRNA and protein levels and putrescine content were greatly increased ( P < 0.05). The polyamine-metabolizing enzyme genes ornithine decarboxylase antizyme 1 (OAZ1) and spermidine / spermine-N1-acetyltransferase (SSAT) were significantly increased, and spermidine synthase (SPDS) was significantly decreased when ODC was downregulated ( P < 0.05). OAZ 1, SPDS and SSAT were significantly increased when ODC was upregulated ( P < 0.05). In addition, after interference with ODC , progesterone (P4) levels in the culture medium of GCs increased greatly ( P < 0.05), while the overexpression of ODC caused the P4 level to decrease significantly ( P < 0.05). After ODC downregulation, granulosa cell activity was significantly reduced, the apoptosis rate was significantly increased, and the BCL-2 / BAX ratio was downregulated ( P < 0.05). Under ODC overexpression, the activity of GCs was notably increased, the apoptosis rate was significantly reduced, and the BCL-2 / BAX protein ratio was upregulated ( P < 0.05). Our study successfully induced ODC interference and overexpression in goose ovarian GCs, and ODC regulated mainly putrescine content in GCs with a slight influence on spermidine and spermine. Moreover, ODC participated in the adjustment of P4 levels in the culture medium of GCs, promoted granulosa cell proliferation and inhibited granulosa cell apoptosis.

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“…The suggested mode of its action is alteration in the level of a polyamine enzyme, ornithine decarboxylase, in utero-fetoplacental complex (Galliani et al, 1986). To compare, a known agent DL 111-IT having a similar activity profile was also studied.…”

Section: In Vitro Assaymentioning

confidence: 99%