Limits...
Ornithine Decarboxylase Activity Is Required for Prostatic Budding in the Developing Mouse Prostate.

Gamat M, Malinowski RL, Parkhurst LJ, Steinke LM, Marker PC - PLoS ONE (2015)

Bottom Line: Inhibiting ornithine decarboxylase using DFMO in UGS organ culture blocked the induction of prostatic buds by androgens, and significantly decreased expression of key prostate transcription factor, Nkx3.1, by androgens.DFMO also significantly decreased the expression of developmental regulatory gene Notch1.Together these results indicate that Odc1 and polyamines are required for androgens to exert their effect in mediating prostatic bud induction, and are required for the expression of a subset of prostatic developmental regulatory genes including Notch1 and Nkx3.1.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI, United States of America.

ABSTRACT
The prostate is a male accessory sex gland that produces secretions in seminal fluid to facilitate fertilization. Prostate secretory function is dependent on androgens, although the mechanism by which androgens exert their effects is still unclear. Polyamines are small cationic molecules that play pivotal roles in DNA transcription, translation and gene regulation. The rate-limiting enzyme in polyamine biosynthesis is ornithine decarboxylase, which is encoded by the gene Odc1. Ornithine decarboxylase mRNA decreases in the prostate upon castration and increases upon administration of androgens. Furthermore, testosterone administered to castrated male mice restores prostate secretory activity, whereas administering testosterone and the ornithine decarboxylase inhibitor D,L-α-difluromethylornithine (DFMO) to castrated males does not restore prostate secretory activity, suggesting that polyamines are required for androgens to exert their effects. To date, no one has examined polyamines in prostate development, which is also androgen dependent. In this study, we showed that ornithine decarboxylase protein was expressed in the epithelium of the ventral, dorsolateral and anterior lobes of the adult mouse prostate. Ornithine decarboxylase protein was also expressed in the urogenital sinus (UGS) epithelium of the male and female embryo prior to prostate development, and expression continued in prostatic epithelial buds as they emerged from the UGS. Inhibiting ornithine decarboxylase using DFMO in UGS organ culture blocked the induction of prostatic buds by androgens, and significantly decreased expression of key prostate transcription factor, Nkx3.1, by androgens. DFMO also significantly decreased the expression of developmental regulatory gene Notch1. Other genes implicated in prostatic development including Sox9, Wif1 and Srd5a2 were unaffected by DFMO. Together these results indicate that Odc1 and polyamines are required for androgens to exert their effect in mediating prostatic bud induction, and are required for the expression of a subset of prostatic developmental regulatory genes including Notch1 and Nkx3.1.

No MeSH data available.


Related in: MedlinePlus

Ornithine decarboxylase expression in the human and mouse adult prostate.In the adult human prostate, ornithine decarboxylase protein was expressed in the basal and luminal cells of the epithelium (A). The negative control with primary antibody omitted showed no staining (B). In the mouse adult prostate, Odc1 mRNA was expressed in the VP, DLP and AP (C), and there was no statistically significant difference in mRNA levels among the lobes. Odc1 mRNA levels were normalized to Hprt. Ornithine decarboxylase protein was expressed in the epithelium of the VP (D), AP (E) and DLP (F). Using immunofluorescence, we observed ornithine decarboxylase staining (green) in close proximity to p63 staining (red), suggesting that ornithine decarboxylase was expressed by present basal as well as luminal epithelial cells (G). Immunostaining for A, B, D-F is in pink. Images were taken at 100X magnification unless otherwise stated. Abbreviations used: BC basal cells, L lumen, LC luminal cells, S stroma.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4591331&req=5

pone.0139522.g001: Ornithine decarboxylase expression in the human and mouse adult prostate.In the adult human prostate, ornithine decarboxylase protein was expressed in the basal and luminal cells of the epithelium (A). The negative control with primary antibody omitted showed no staining (B). In the mouse adult prostate, Odc1 mRNA was expressed in the VP, DLP and AP (C), and there was no statistically significant difference in mRNA levels among the lobes. Odc1 mRNA levels were normalized to Hprt. Ornithine decarboxylase protein was expressed in the epithelium of the VP (D), AP (E) and DLP (F). Using immunofluorescence, we observed ornithine decarboxylase staining (green) in close proximity to p63 staining (red), suggesting that ornithine decarboxylase was expressed by present basal as well as luminal epithelial cells (G). Immunostaining for A, B, D-F is in pink. Images were taken at 100X magnification unless otherwise stated. Abbreviations used: BC basal cells, L lumen, LC luminal cells, S stroma.

Mentions: In the human prostate, ornithine decarboxylase protein was expressed in the cytoplasm of the epithelium in both basal and luminal epithelial cells (Fig 1A), consistent with previous studies [25,26]. The negative control, with primary antibody omitted, showed no staining (Fig 1B). Previous work has shown that ornithine decarboxylase protein is expressed in the epithelium of the mouse prostate, however the prostate lobe examined was not specified [25]. To further characterize ornithine decarboxylase expression in the mouse prostate, we examined Odc1 mRNA levels in the different lobes of the mouse prostate (ventral prostate VP, anterior prostate AP and dorsolateral prostate DLP). We found that Odc1 mRNA was expressed in all three lobes and they did not differ significantly in Odc1 mRNA levels (Fig 1C). We also observed ornithine decarboxylase protein in the prostate epithelium in the VP, DLP and AP (Fig 1D, 1E and 1F), which is consistent with previous work [25].


Ornithine Decarboxylase Activity Is Required for Prostatic Budding in the Developing Mouse Prostate.

Gamat M, Malinowski RL, Parkhurst LJ, Steinke LM, Marker PC - PLoS ONE (2015)

Ornithine decarboxylase expression in the human and mouse adult prostate.In the adult human prostate, ornithine decarboxylase protein was expressed in the basal and luminal cells of the epithelium (A). The negative control with primary antibody omitted showed no staining (B). In the mouse adult prostate, Odc1 mRNA was expressed in the VP, DLP and AP (C), and there was no statistically significant difference in mRNA levels among the lobes. Odc1 mRNA levels were normalized to Hprt. Ornithine decarboxylase protein was expressed in the epithelium of the VP (D), AP (E) and DLP (F). Using immunofluorescence, we observed ornithine decarboxylase staining (green) in close proximity to p63 staining (red), suggesting that ornithine decarboxylase was expressed by present basal as well as luminal epithelial cells (G). Immunostaining for A, B, D-F is in pink. Images were taken at 100X magnification unless otherwise stated. Abbreviations used: BC basal cells, L lumen, LC luminal cells, S stroma.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591331&req=5

pone.0139522.g001: Ornithine decarboxylase expression in the human and mouse adult prostate.In the adult human prostate, ornithine decarboxylase protein was expressed in the basal and luminal cells of the epithelium (A). The negative control with primary antibody omitted showed no staining (B). In the mouse adult prostate, Odc1 mRNA was expressed in the VP, DLP and AP (C), and there was no statistically significant difference in mRNA levels among the lobes. Odc1 mRNA levels were normalized to Hprt. Ornithine decarboxylase protein was expressed in the epithelium of the VP (D), AP (E) and DLP (F). Using immunofluorescence, we observed ornithine decarboxylase staining (green) in close proximity to p63 staining (red), suggesting that ornithine decarboxylase was expressed by present basal as well as luminal epithelial cells (G). Immunostaining for A, B, D-F is in pink. Images were taken at 100X magnification unless otherwise stated. Abbreviations used: BC basal cells, L lumen, LC luminal cells, S stroma.
Mentions: In the human prostate, ornithine decarboxylase protein was expressed in the cytoplasm of the epithelium in both basal and luminal epithelial cells (Fig 1A), consistent with previous studies [25,26]. The negative control, with primary antibody omitted, showed no staining (Fig 1B). Previous work has shown that ornithine decarboxylase protein is expressed in the epithelium of the mouse prostate, however the prostate lobe examined was not specified [25]. To further characterize ornithine decarboxylase expression in the mouse prostate, we examined Odc1 mRNA levels in the different lobes of the mouse prostate (ventral prostate VP, anterior prostate AP and dorsolateral prostate DLP). We found that Odc1 mRNA was expressed in all three lobes and they did not differ significantly in Odc1 mRNA levels (Fig 1C). We also observed ornithine decarboxylase protein in the prostate epithelium in the VP, DLP and AP (Fig 1D, 1E and 1F), which is consistent with previous work [25].

Bottom Line: Inhibiting ornithine decarboxylase using DFMO in UGS organ culture blocked the induction of prostatic buds by androgens, and significantly decreased expression of key prostate transcription factor, Nkx3.1, by androgens.DFMO also significantly decreased the expression of developmental regulatory gene Notch1.Together these results indicate that Odc1 and polyamines are required for androgens to exert their effect in mediating prostatic bud induction, and are required for the expression of a subset of prostatic developmental regulatory genes including Notch1 and Nkx3.1.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, WI, United States of America.

ABSTRACT
The prostate is a male accessory sex gland that produces secretions in seminal fluid to facilitate fertilization. Prostate secretory function is dependent on androgens, although the mechanism by which androgens exert their effects is still unclear. Polyamines are small cationic molecules that play pivotal roles in DNA transcription, translation and gene regulation. The rate-limiting enzyme in polyamine biosynthesis is ornithine decarboxylase, which is encoded by the gene Odc1. Ornithine decarboxylase mRNA decreases in the prostate upon castration and increases upon administration of androgens. Furthermore, testosterone administered to castrated male mice restores prostate secretory activity, whereas administering testosterone and the ornithine decarboxylase inhibitor D,L-α-difluromethylornithine (DFMO) to castrated males does not restore prostate secretory activity, suggesting that polyamines are required for androgens to exert their effects. To date, no one has examined polyamines in prostate development, which is also androgen dependent. In this study, we showed that ornithine decarboxylase protein was expressed in the epithelium of the ventral, dorsolateral and anterior lobes of the adult mouse prostate. Ornithine decarboxylase protein was also expressed in the urogenital sinus (UGS) epithelium of the male and female embryo prior to prostate development, and expression continued in prostatic epithelial buds as they emerged from the UGS. Inhibiting ornithine decarboxylase using DFMO in UGS organ culture blocked the induction of prostatic buds by androgens, and significantly decreased expression of key prostate transcription factor, Nkx3.1, by androgens. DFMO also significantly decreased the expression of developmental regulatory gene Notch1. Other genes implicated in prostatic development including Sox9, Wif1 and Srd5a2 were unaffected by DFMO. Together these results indicate that Odc1 and polyamines are required for androgens to exert their effect in mediating prostatic bud induction, and are required for the expression of a subset of prostatic developmental regulatory genes including Notch1 and Nkx3.1.

No MeSH data available.


Related in: MedlinePlus