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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

Odc1 mRNA levels in the developing urogenital sinus and in separated UGS tissue compartments.Odc1 transcripts were present in the male and female UGS throughout the period of prostatic bud induction from E15-E18, although they did not vary between males and females during this period (A). Odc1 transcript abundance did not differ between the epithelium and mesenchyme at E16 (B), although there were significantly more Odc1 transcripts in the mesenchyme compared to the epithelium at E18 (B). Abbreviations used: epi epithelium, mes mesenchyme. *, p<0.05.
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pone.0139522.g002: Odc1 mRNA levels in the developing urogenital sinus and in separated UGS tissue compartments.Odc1 transcripts were present in the male and female UGS throughout the period of prostatic bud induction from E15-E18, although they did not vary between males and females during this period (A). Odc1 transcript abundance did not differ between the epithelium and mesenchyme at E16 (B), although there were significantly more Odc1 transcripts in the mesenchyme compared to the epithelium at E18 (B). Abbreviations used: epi epithelium, mes mesenchyme. *, p<0.05.

Mentions: We assessed the mRNA levels of Odc1 in the developing UGS in both male and female mice during embryogenesis using quantitative PCR (qPCR). Odc1 mRNA was expressed in both the male and female UGS during the period when prostatic buds are forming from embryonic day 15 to embryonic day 18 (Fig 2A). However Odc1 mRNA levels did not differ between males and females during the period of prostatic bud formation (Fig 2A).


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)

Odc1 mRNA levels in the developing urogenital sinus and in separated UGS tissue compartments.Odc1 transcripts were present in the male and female UGS throughout the period of prostatic bud induction from E15-E18, although they did not vary between males and females during this period (A). Odc1 transcript abundance did not differ between the epithelium and mesenchyme at E16 (B), although there were significantly more Odc1 transcripts in the mesenchyme compared to the epithelium at E18 (B). Abbreviations used: epi epithelium, mes mesenchyme. *, p<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139522.g002: Odc1 mRNA levels in the developing urogenital sinus and in separated UGS tissue compartments.Odc1 transcripts were present in the male and female UGS throughout the period of prostatic bud induction from E15-E18, although they did not vary between males and females during this period (A). Odc1 transcript abundance did not differ between the epithelium and mesenchyme at E16 (B), although there were significantly more Odc1 transcripts in the mesenchyme compared to the epithelium at E18 (B). Abbreviations used: epi epithelium, mes mesenchyme. *, p<0.05.
Mentions: We assessed the mRNA levels of Odc1 in the developing UGS in both male and female mice during embryogenesis using quantitative PCR (qPCR). Odc1 mRNA was expressed in both the male and female UGS during the period when prostatic buds are forming from embryonic day 15 to embryonic day 18 (Fig 2A). However Odc1 mRNA levels did not differ between males and females during the period of prostatic bud formation (Fig 2A).

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