NCBI Summary:
This gene encodes the rate-limiting enzyme of the polyamine biosynthesis pathway which catalyzes ornithine to putrescine. The activity level for the enzyme varies in response to growth-promoting stimuli and exhibits a high turnover rate in comparison to other mammalian proteins. Originally localized to both chromosomes 2 and 7, the gene encoding this enzyme has been determined to be located on 2p25, with a pseudogene located on 7q31-qter.
Deficiency of ovarian ornithine decarboxylase contributes to aging-related egg aneuploidy in mice. Tao Y et al. It has been known for more than four decades that during mammalian estrous cycles, luteinizing hormone stimulates a transitory rise in the ovaries of ornithine decarboxylase (ODC) activity and its enzymatic product putrescine, concurrent with oocyte maturation in vivo. Inhibition of this transitory ODC/putrescine rise, however, does not appear to affect oocyte maturation or ovulation. Using several mouse models and combining in vitro and in vivo approaches, we demonstrated that deficiency of ODC during oocyte maturation is correlated with increased levels of egg aneuploidies. These results suggest that the transitory ovarian ODC rise in late proestrus is important for ensuring proper chromosome segregation during oocyte maturation. Older mice (8 months of age) exhibited about 1/3 that of young mice in LH-stimulated ovarian ODC activity and a corresponding increase of egg aneuploidies. Moreover, a combination of putrescine supplementation in mouse drinking water leading up to oocyte retrieval and in oocyte maturation medium reduced egg aneuploidies of the older mice from 12.7% to 5.3%. Therefore, ovarian ODC deficiency might be an important etiology of maternal aging-related aneuploidies, and peri-ovulatory putrescine supplementation might reduce the risk of aneuploid conceptions in older women. 2012 The Authors Aging Cell 2012 Blackwell Publishing Ltd/Anatomical Society of GreatBritain and Ireland.
The preovulatory rise of ovarian ornithine decarboxylase is required for progesterone secretion by the corpus luteum. Bastida CM et al. Ovarian progesterone secretion during the diestrus stage of the estrous cycle is produced by luteal cells derived from granulosa and thecal cells after the differentiation process that follows ovulation. Our results show that blockade of the preovulatory rise of ovarian ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, by treatment with the specific inhibitor alpha-difluoromethylornithine (DFMO) leads to a significant decrease in the ovarian progesterone content and a dramatic fall in the plasma levels of this hormone during the following diestrus. The same inhibition was produced in spite of the fact that both luteinizing and follicle stimulating hormones were given concomitantly with DFMO. On the other hand, the acute rise in the plasma progesterone levels observed after administration of human chorionic gonadotropin to mice at different periods of the estrous cycle was not affected by DFMO administration. Our results indicate that although elevated levels of ODC are not required for acute ovarian steroidogenesis, the preovulatory peak of ovarian ODC activity observed in the evening of proestrus may be critical for the establishment of a constitutive steroidogenic pathway and progesterone secretion by the corpus luteum during the diestrus stage of the murine estrous cycle.
Dissociated regulation of cellular progesterone secretion and cytosolic ornithine decarboxylase activity in isolated ovarian cells in vitro.
Veldhuis JD, et al have utilized isolated, highly differentiated porcine granulosa cells maintained under chemically defined conditions in vitro to examine directly the relationship between ornithine decarboxylase (ODC) activity and progesterone secretion in ovarian cells. The administration of saturating concentrations of LH, prostaglandin E2, L-epinephrine, or 8-bromo-cAMP each elicited highly significant increases in progesterone production, which correlated closely with corresponding stimulated levels of ODC activity. Highly purified preparations of FSH elicited no enzymatic or steroidogenic response. ODC activity and progesterone production also correlated closely after administration of various inhibitors of protein or RNA synthesis . However, in time-course experiments, progesterone secretion increased significantly before the rise of ODC activity. Furthermore, a direct irreversible catalytic inhibitor of ODC activity, DL-alpha-difluoromethylornithine, and three indirect inhibitors of ODC that putatively induce intracellular antizyme, produced profound suppression of enzymatic activity, without altering maximal progesterone production in response to LH. Thus, the current studies close parallelism between hormonal regulation of ODC activity and progesterone production in ovarian cells in vitro. However, our ability to demonstrate apparent dissociation between these two processes suggests that hormonal stimulation of steroidogenesis may not be obligatorily coupled to the rapidly turning-over cytosolic protein ODC.
Bastida CM, et al reported the influence of ovarian ornithine decarboxylase in folliculogenesis and luteinization.
LH plays a relevant role in folliculogenesis, ovulation and luteinization. Although ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is a target of LH in the ovary, the functional significance of ODC induction has remained elusive. Our study reveals that the blockade of the induction of ovarian ODC by means of the specific inhibitor alpha-difluoromethylornithine (DFMO) affects folliculogenesis and luteinization. In immature female mice DFMO was found to inhibit ovarian growth, the formation of Graafian follicles and the secretion of progesterone and estradiol In adult cycling females, the administration of DFMO at the evening/night of proestrus, markedly decreased plasma progesterone levels at diestrus, what was associated to the decrease in the expression of steroidogenic factor 1, cytochrome P450scc enzyme and StAR protein in the ovary, and to a reduced vascularization of the corpora lutea. These effects were not reverted by the administration of gonadotropins or prolactin. ODC immunoreactivity was also stimulated by LH in theca and granulosa cells of antral follicles but not in preantral follicles. In overall, these experiments demonstrate that elevated ODC values found in the ovary of immature and adult mice play a relevant function in ovarian physiology, and that ODC/polyamines must be considered as important mediators of some of the effects of LH on follicular development and luteinization.
Gonadotropin stimulation of porcine ovarian ornithine decarboxylase in vitro: the role of 3',5'-adenosine monophosphate. Osterman J et al. The role of cAMP as a mediator of gonadotropin stimulation of ovarian ornithine decarboxylase (ODC) activity was studied in granulosa cells isolated from small (1--2 mm) porcine ovarian follicles. These cells responded to both FSH and LH with significant increases in intracellular concentration of cAMP. At concentrations of gonadotropins which were saturating for the induction of ODC activity, FSH was a more potent stimulator of both cAMP production and ODC activity than LH. N,O'-Dibutyryl cAMP (1.0--10.0 mM) caused a dose-dependent stimulation of ODC activity which equaled the maximal effect of LH but was significantly less effective than the saturating dose of FSH. 8-Bromo-cAMP was more potent than N,O'-dibutyryl cAMP and as effective as FSH as an inducer of ODC activity. Addition of theophylline, a phosphodiesterase inhibitor, to the incubation medium resulted in a dose-dependent inhibition of ODC activity in both control and gonadotropin-stimulated cells. In contrast, 1-methyl,3-isobutyl xanthine, another phosphodiesterase inhibitor, potentiated effects of both submaximal and maximal effective doses of gonadotropins while producing no effect on basal ODC activity of these cells. The results of this study are consistent with the concept that cAMP can mediate gonadotropin stimulation of ODC in porcine granulosa cells. In addition, this study shows the importance of proper selection of cAMP analogs and phosphodiesterase inhibitors, and their concentration in studying such effects.
Expression regulated by
FSH, LH
Comment
Regulation of ovarian ornithine decarboxylase activity and its mRNA by gonadotropins in the immature rat.
Weiner KX, et al .
Previous studies have demonstrated that gonadotropin increases ornithine decarboxylase (ODC) activity in the rat ovary. The increase of ODC activity following gonadotropin stimulation is localized primarily to proliferating granulosa cells. The present studies were undertaken to characterize the mechanism of this hormone-induced increase of ODC. A single intraperitoneal injection of PMSG resulted in a 15-fold increase in ODC activity (p < 0.0001). Activity was maximal 1 day following PMSG administration, and thereafter declined with time. PMSG also induced an increase in ODC mRNA levels (p < 0.0001). However, ODC mRNA increased only 2-fold, as compared with a 15-fold increase in ODC activity. Actin mRNA levels were unaffected by PMSG. These results demonstrate that PMSG-induced increase in ODC activity cannot be fully explained by an increase in ODC mRNA, thus indicating that part of the regulation of ODC by PMSG is occurring at the translational and/or posttranslational level. Such regulation is likely a necessary dimension of the fine control of the levels/activity of this important enzyme which has a very short half-life.
White SS, Ojeda SR reported changes in ovarian luteinizing hormone and follicle-stimulating hormone receptor content and in gonadotropin-induced ornithine decarboxylase activity during prepubertal and pubertal development of the female rat.
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Ovarian hCG and FSH receptor content was measured at different postnatal ages (days 4-32), at 4-day intervals, and expressed as counts per min 125I-labeled hormone bound/micrograms DNA. Specific FSH binding was minimal at day 4 and increased to a maximum at day 28, with the greatest rate of increase between day 4 and 16. hCG receptor content increased 6-fold between day 4 and 32, but contrasting with FSH, its greatest rate of increase occurred between day 16 and 28. The effectiveness of in vivo treatment with LH in inducing ovarian ornithine decarboxylase (ODC) activity, measured in 20,000 X g supernatants by the in vitro formation of 14CO2 from labeled ornithine, increased significantly during prepubertal development (days 21-33), paralleling the changes in hCG receptors. Ovarian hCG and FSH receptor content was also measured during the time of puberty. Specific hCG binding increased from anestrus (juvenile 32-day-old animals) to 1300 h of the first proestrus. The levels declined significantly by 1600 h of first proestrus and reached minimal values by the morning of estrus. Specific FSH binding also increased from anestrus to first proestrus, but to a much lesser degree, the levels showing only minor fluctuations during the rest of the cycle. hCG receptors measured in granulosa cells during puberty increased to an even greater extent than in the whole ovary; binding exhibited an 8-fold increase from anestrus to 1300 h of first proestrus and then declined to much lower values on estrus and the first diestrus. The capacity of LH to induce ovarian ODC activity increased markedly between anestrus and first proestrus, declining thereafter, and again paralleled the changes in LH receptor content. Evaluation of the kinetics of binding of hCG and FSH with their respective receptors in ovaries of 28-day-old rats revealed that the binding of hCG reached equilibrium within 4-8 h, whereas the binding of FSH attained equilibrium between 12-24 h. In both cases, however, the labeled hormones were clearly dissociable from their respective receptors by addition of an excess of unlabeled hormone. Moreover, although the ovarian receptor content of both hCG and FSH increased during prepubertal development, the equilibrium association constant of either hormone with its receptor remained unchanged. The results suggest that the infantile increase in FSH receptors may be induced by the high serum FSH levels present at that age and that, as shown by others in hypophysectomized rats, the subsequent increase in hCG receptors is, at least in part, an FSH-dependent phenomenon. The parallel changes in hCG receptors and LH-induced ODC activity during pre- and peripubertal development strongly suggest that an increase in LH binding capacity plays a fundamental role in the process of ovarian growth. It is also suggested that the changes in the steroidogenic ovarian response to hCG previously observed in peripubertal rats are, at least in part, determined by changes in ovarian LH receptor content.
Ovarian localization
Granulosa, Theca
Comment
Cellular origin of prolonged induction of ornithine decarboxylase in the rat ovary.
Lee CY, et al .
The temporal changes of ornithine decarboxylase (ODC) activity were investigated in the immature rat ovary following a single subcutaneous injection of pregnant mare serum gonadotropin (PMSG). A dose-response relationship was established. Maximal ODC activity was obtained at a dose of 25 IU of PMSG. This increase in ODC activity was accompanied by an increase of ovarian weight before reaching a maximum. A 250-fold increase of ODC activity was observed 1 day following a single dose of PMSG (50 IU). The enzyme specific activity only returned to the control level 4-5 days after hormone treatment. Immunoreactive ODC in immature, PMSG-primed rat ovaries and in heavily luteinized rat ovaries was localized utilizing the immunoperoxidase method and an antibody to ODC. Immunoreactive enzyme was confined to the cytoplasm of the granulosa cells but was not present in luteal cells. Thecal cells showed only weak immunostaining. This study provides clear evidence that the granulosa cell is the unique source of ODC activity in response to PMSG treatment. Furthermore, these data support the concept that polyamines play a role in granulosa cell proliferation and hence follicular development.
Follicle stages
Preovulatory
Comment
Distribution of ornithine decarboxylase in ovaries of rat and hamster during pro-oestrus. Persson L et al. The biosynthesis of polyamines is dramatically increased in the ovaries of rat and hamster during the evening of pro-oestrus. In an attempt to shed some light on the physiological function of this biosynthesis ornithine decarboxylase (ODC), which catalyzes the rate-limiting step in the biosynthesis of the polyamines, was immunohistochemically localized in the ovaries from rat and hamster during pro-oestrus. At dioestrus, only a few immunoreactive cells were found in the ovaries. During the evening of pro-oestrus, on the other hand, numerous immunoreactive cells were observed in the ovaries. These cells were confined to the internal thecal layer of Graafian as well as smaller follicles and to the interstitial tissue of the ovary. The granulosa cells appeared to be devoid of immunoreactive ODC. The hamster ovary, which during this time exhibited considerably higher levels of ODC activity than the ovaries from the rat, did accordingly contain more immunoreactive cells than the rat ovary.