help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Huang, H. F. S.
Right arrow Articles by Irwin, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huang, H. F. S.
Right arrow Articles by Irwin, R. J.
Endocrinology Vol. 138, No. 2 553-559
Copyright © 1997 by The Endocrine Society

Articles

Androgen Modulation of the Messenger Ribonucleic Acid of Retinoic Acid Receptors in the Prostate, Seminal Vesicles, and Kidney in the Rat1

Hosea F. S. Huang, Ming-tang Li, Stanley Von Hagen, Yuan Fang Zhang2 and Robert J. Irwin

Department of Surgery, Section of Urology (H.F.S.H., M.T.L., R.J.I.), Department of Pharmacology, Physiology, and Toxicology (S.V.H.), and Preventive Medicine and Community Health Biostatistics Division (S.V.H.), University of Medicine and Dentistry of New Jersey Medical School, Newark, New Jersey 07103; and the Veterans Affair Medical Center (H.F.S.H.), East Orange, New Jersey 07019

Address all correspondence and requests for reprints to: Dr. Hosea F. S. Huang, Department of Surgery Section of Urology, University of Medicine and Dentistry of New Jersey Medical School, 185 South Orange Avenue, Newark, New Jersey 07103.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Previously, we reported that the steady state level of messenger RNA (mRNA) transcripts of retinoic acid receptors (RAR) {alpha} and {gamma} in the testes of 20-day-old rats can be modulated by exogenous testosterone. These results suggest that androgen regulation of Sertoli cell functions may involve biochemical events mediated by RAR genes. In this study, we examined the effects of castration and testosterone replacement on the steady state level of mRNA transcripts for RAR{alpha} and {gamma} in the prostate, seminal vesicles, and kidney of the rat. Northern blot analysis revealed that in intact adult rats, the relative steady state levels of the 3.4- and 2.7-kilobase (kb) mRNA transcripts for RAR{alpha} and the 3.4-kb transcript for RAR{gamma} in the prostate were at least 20-fold higher than those in the seminal vesicles and kidney. The relatively high abundance of RAR mRNA transcripts in the prostate suggests the physiological importance of RAR-mediated processes in this organ. Castration resulted in an increase in the level of RAR mRNA transcripts in the prostate and seminal vesicles, reaching a maximum of 2- to 4-fold in the prostate and 15- to 23-fold in the seminal vesicles within 6 days. On the other hand, the levels of mRNA transcripts of RAR{alpha} and -{gamma} in the kidney were reduced by 40–50% 1 day after castration. The effects of castration on RAR mRNA levels in all three organs were prevented by implantation of 3-cm testosterone capsules at the time of castration, a regimen that provides physiological levels of serum testosterone.

In a subsequent experiment, adult male rats were given a single sc injection of 2 mg testosterone 3 days after castration. This treatment resulted in an acute suppression of the level of RAR mRNA transcripts in all three organs within 30 min. Thereafter, the levels of RAR{alpha} and -{gamma} mRNA transcripts in the prostate continued to decrease, whereas those in the seminal vesicles returned to the castrated levels within 6 h. On the other hand, RAR mRNA levels in the kidney rebounded by 1 h and remained at the level found in the untreated castrated rats.

These results demonstrate that the steady state level of mRNA transcripts for RAR{alpha} and -{gamma} in the prostate, seminal vesicles, and kidney can be modulated by testosterone in organ-specific manners, thus suggesting that the RAR-mediated processes may be involved in the effects of androgen in these organs. Furthermore, the relatively low increment in prostatic RAR mRNA levels after castration compared to that in the seminal vesicles demonstrates a difference in androgen responses between these two organs. This difference could dictate the efficacy of the effects of androgen on cellular function and may contribute to the disparate vulnerabilities to androgen-related uncontrolled cell proliferation and/or malignancy in the prostate and seminal vesicles.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
THE DEVELOPMENT and function of male accessory glands, the prostate and seminal vesicles, are well documented androgen-dependent processes. Androgen ablation results in a decrease in overall cellular activities and an increase in cell death, leading to the regression of these organs (1, 2, 3, 4). In addition to these male accessory organs, the presence of androgen receptor and androgen modulation of cellular activities have been reported in many other organs, including the kidney, even though these organs do not require androgen for normal function (5, 6). Androgen exerts its biological effects by binding to the nuclear androgen receptor in target cells. The cascade of biochemical events initiated by this ligand-receptor interaction is, in turn, responsible for numerous changes in cellular activities (7, 8). Differences in post-receptor events are probably responsible for the varying effects of androgen in different organs. Thus, identification of an androgen-responsive gene(s) and the molecular events elicited by these genes may provide a new understanding of the mode of androgen actions in different organs. Recently, Huang et al. (9) reported that administration of a single dose of 1 mg testosterone to 20-day-old rats resulted in acute, but diverse, responses of the steady state levels of messenger RNA (mRNA) for retinoic acid receptors (RAR) {alpha} and {gamma} in the testis. This observation demonstrated that the RAR genes can be modulated by androgen and suggests that RAR-mediated processes may be involved in the androgen regulation of Sertoli cell functions.

RARs are important in mediating the biological actions of retinoic acid that are essential for normal cell proliferation, differentiation, and development (10, 11, 12). Therefore, understanding the effects of androgen on the expression of RAR genes in organs in which cell proliferation and functions are sensitive to androgen manipulation and also in organs that are independent of androgen for normal function may provide new insights into the mechanisms that determine the cellular effects of androgen in different organs. In this study, we examined the effects of castration and testosterone replacement on the expression of mRNA for RAR{alpha} and -{gamma} in the prostate, seminal vesicles, and kidney of adult rats.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Animals
Adult Sprague-Dawley rats (300–350 g; Toconic Farm, Toconic, NY) were maintained in an air-conditioned and light-controlled animal room for 2 weeks before the experiment. Animals were fed Purina rat chow (Ralston Purina, St. Louis, MO) and water ad libitum.

Exp 1.
Animals were lightly anesthetized with ether, and both testes were removed surgically through a midscrotal incision. Animals were killed 1–6 days after castration. In some animals (n = 4), a 3-cm testosterone capsule was implanted sc on the back immediately after castration. These animals were also killed 6 days later. The prostate gland, seminal vesicles, and kidney were dissected on an ice-cold petri dish, frozen on dry ice, and stored at -80 C for subsequent analysis.

Exp 2.
Castrated male rats were given a single sc injection of 2 mg testosterone 3 days after castration. Animals were killed 0.5–6 h later. The prostate gland, seminal vesicles, and kidney were dissected, frozen, and stored at -80 C.

RNA isolation and Northern blot hybridization
Total RNA were isolated from different tissues by the single step method described by Chomczynski and Sacchi (13). Tissues were homogenized with a Polytron homogenizer (Brinkmann Instruments, Westbury, NY) in 5 vol denaturing solution containing 4 M guanidine thiocyanate; 25 mM sodium citrate, pH 7.0; 0.5% sarcosyl; and 0.1 M 2-mercaptoethanol. After the phenol and chloroform-isoamyl alcohol extraction, the RNA in the aqueous phase was precipitated with 1 vol isopropanol at -20 C overnight and dried under a vacuum. The polyadenylated [poly(A)+] RNAs were subsequently isolated by oligo(deoxythymidine)-cellulose chromatography (14), separated electrophoretically on a 1% agarose-17% formaldehyde gel (15), and blotted onto a Biotrans membrane (ICN Biomedical, Costa Mesa, CA). The complementary DNA (cDNA) probes of mouse RAR{alpha}, -ß, and -{gamma} (16, 17) were isolated by agarose electrophoresis after appropriate endonucleases digestion and radiolabeled with [32P]deoxy-CTP, using a random priming kit (Boehringer Mannheim, Indianapolis, IN). The blots were prehybridized for 2–4 h in a solution containing 6 x SSC (150 mM NaCl and 15 mM sodium citrate, pH 7.0), 0.5% SDS, 50% formamide, and 100 µg/ml denatured sperm DNA at 42 C, then hybridized overnight in the same buffer containing approximately 106 cpm/ml radiolabeled cDNA probe. The membranes were washed in 1 x SSC solution containing 0.1% SDS at 68 C for 20–30 min, followed by several changes in 0.2 x SSC and 0.1% SDS at 68 C for 2–4 h. After exposure to Kodak XAR-5 film (Eastman Kodak, Rochester, NY) with an intensifying screen for 2–10 days, the radioautographs were developed. The membranes were subsequently stripped and rehybridized with 32P-labeled ß-actin cDNA and/or cDNA for 18S ribosomal RNA.

The relative abundance of different transcripts [RAR{alpha}, 3.4 and 2.7 kilobases (kb); RAR{gamma}, 3.4 kb; 18S ribosomal RNA] were estimated by densitometric scanning by means of a Shimadzu densitometer and integrator (Shimadzu Scientific Instruments, Princeton, NJ). Because castration resulted in an increase in the steady state level of ß-actin mRNA (data not shown), the steady state level of each mRNA transcript of RAR{alpha} or -{gamma}, as estimated by the area under the curve, was normalized against that of the 18S ribosomal RNA in each sample. The ratio between the RAR mRNA and the 18S ribosomal RNA of the normal control in each blot was considered 100%, and results of experimental samples were expressed as the percentage of normal control animals in each blot.

Statistics
ANOVA was employed to detect the effects of castration and testosterone replacement on the RAR mRNA levels within each organ, using the JMP statistical software package (SAS Institute, Cary, NC). Subsequently, Dunnett’s multiple range test was used to compare the means of the castrated rats and the normal controls or the means of the testosterone-replaced castrated rats and the untreated castrated animals. When the 95% confident level of the experimental samples did not overlap with 100%, the mean of that experimental group was said to be statistically different from the control mean.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Organ distribution of RAR mRNA
Figure 1Go shows the Northern blot analysis of organ distribution of RAR{alpha} and -{gamma} mRNA in intact adult rats. The steady state levels of the 3.4- and 2.7-kb mRNA transcripts of RAR{alpha} and the 3.4-kb RAR{gamma} mRNA in the prostate were estimated to be at least 20-fold higher than those in the seminal vesicles, kidney, and spleen. Although the level of RAR{alpha} mRNA transcripts in the prostate was comparable to that in the testis, the 3.4-kb RAR{gamma} mRNA was at least 20-fold higher than that in the testis. Attempts have also been made to measure RARß mRNA, but the results were inconclusive due to very weak signal of RARß, high background of the radiographs after prolonged exposure, and, frequently, inconsistency among replicates.



View larger version (71K):
[in this window]
[in a new window]
  		Figure 1. Northern blot analysis of the distribution of mRNA transcripts for RAR{alpha} and -{gamma} in the testis, prostate, seminal vesicle, kidney, and spleen of adult male rats. Each lane contained 12 µg poly(A)+ RNA isolated by oligo(deoxythymidine)-cellulose chromatography; radiograms were developed after 2 days of exposure.

 
Castration effect on RAR mRNA
Castration resulted in an increase in the levels of the 3.4- and 2.7-kb transcripts of RAR{alpha} and the 3.4-kb transcript for RAR{gamma} in the prostate by more than 80% 1 day after castration (P < 0.05; Table 1Go) and continued to increase to a maximum of 2- to 4-fold within 3–6 days (Fig. 2Go). Implantation of a 3-cm testosterone capsule, a regimen that restores normal serum testosterone levels (18), prevented the castration-induced increases in mRNA levels of both RAR{alpha} and -{gamma}.


View this table:
[in this window]
[in a new window]
  		Table 1. Quantitative analysis of the effects of castration on the steady state level of RAR mRNA transcripts

 


View larger version (35K):
[in this window]
[in a new window]
  		Figure 2. Time course of the effect of castration on the steady state level of mRNA for RAR{alpha} and -{gamma} in the prostate. Animals were killed 1–6 days after castration. A, Representative Northern blot analysis. Each lane contained 10 µg poly(A)+ RNA, and radiograms were developed after 2 days of exposure. NC, Normal control; Cx, castrated rats. B, Quantitative comparison of effect of castration on mRNA transcripts of RAR{alpha} and -{gamma}. Results are the mean of four animals, expressed as percentage of the mean in four normal controls (broken line). The shaded areas represent the largest 95% confidence limits of the three transcripts.

 
The steady state levels of mRNA transcripts for RAR{alpha} and -{gamma} in the seminal vesicles were also increased by 2- to 5-fold 1 day after castration (P < 0.05; Fig. 3Go and Table 1Go) and continued to increase to 15- to 24-fold above those of the normal controls within 6 days. Although such an increase was also attenuated by exogenous testosterone, the levels of RAR{alpha} mRNA transcripts in the seminal vesicles of testosterone-implanted castrated rats remained 2- to 7-fold above those of the normal controls (P < 0.05).



View larger version (40K):
[in this window]
[in a new window]
  		Figure 3. Effects of castration on the level of mRNA for RAR{alpha} and -{gamma} in the seminal vesicles. A, Northern blot analysis. Each lane contained 15 µg poly(A)+ RNA, and radiograms were developed after 7 days of exposure. B, Quantitative analysis of the effect of castration on mRNA transcripts of RAR{alpha} and -{gamma}. See Fig. 2Go for other details.

 
On the other hand, there was a 40–50% decrease in the levels of the mRNA transcripts of both RAR{alpha} and -{gamma} in the kidney 1 day after castration (P < 0.05; Fig. 4Go); this effect tended to continue, but the decline was not statistically significant (P > 0.10). Although the effect of castration on renal RAR mRNA transcripts was also attenuated by exogenous testosterone, RAR mRNA levels in the kidney of testosterone-implanted rats remained lower than those in the normal controls (P < 0.05; Table 1Go).



View larger version (39K):
[in this window]
[in a new window]
  		Figure 4. The effect of castration on the level of mRNA for RAR{alpha} and -{gamma} in the kidney. A, Northern blot analysis. Each lane contained 15 µg poly(A)+ RNA, and radiograms were developed after 7 days of exposure. B, Quantitative analysis of effect of castration on mRNA transcripts of RAR{alpha} and -{gamma}. See Fig. 2Go for other details.

 
Acute effect of testosterone on RAR mRNA in castrated rats
Administration of 2 mg exogenous testosterone to 3 day postcastrated rats resulted in a 20–30% decrease in the steady state level of mRNA transcripts for RAR{alpha} and -{gamma} in the prostate within 30 min (P < 0.05; Fig. 5Go and Table 2Go). This effect continued at least 6 h after testosterone administration. The level of mRNA for RAR{alpha} and -{gamma} in the seminal vesicles of the castrated rats also decreased after testosterone injection, but had rebounded by 6 h (Table 2Go).



View larger version (33K):
[in this window]
[in a new window]
  		Figure 5. Acute effects of testosterone on the level of mRNA for RAR{alpha} and -{gamma} in the prostate 3 days after castration. Animals were killed at various times (0.5–6 h) after sc injection of 2 mg testosterone. A, Northern blot analysis. Each lane contained 8 µg poly(A)+ RNA, and radiograms were developed after 4 days of exposure. NC, Normal control; Cx, 3 days after castration. B, Quantitative analysis of the acute effect of testosterone replacement on the level of mRNA transcripts of RAR{alpha} and -{gamma}. Results are the mean of four animals, expressed as percentage of the mean of four castrated controls (broken line). The shaded areas represent the largest 95% confidence limits of the three transcripts.

 

View this table:
[in this window]
[in a new window]
  		Table 2. Quantitative analysis of the effects of testosterone replacement on the steady state level of RAR mRNA transcripts in castrated rats

 
The levels of RAR mRNAs in the kidney of castrated rats decreased acutely within 30 min after the administration of testosterone (Fig. 6Go). Although RAR{alpha} and -{gamma} mRNA in the kidney rebounded to a level above that in the untreated castrated rats by 1 h (P < 0.05; Table 2Go), they remained at the castrated levels 3–6 h after testosterone treatment.



View larger version (36K):
[in this window]
[in a new window]
  		Figure 6. Acute effects of testosterone replacement on the level of mRNA transcripts for RAR{alpha} and -{gamma} in the kidney of 3-day postcastrated rats. A, Northern blot analysis. Each lane contained 8 µg poly(A)+ RNA, and radiograms were developed after 4 days of exposure. B, Quantitative analysis of the acute effect of testosterone replacement on mRNA levels of RAR{alpha} and -{gamma}. See Figs. 2Go and 5Go for other details.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
RARs are members of the steroid-thyroid hormone receptor superfamily, which are ligand-induced transcriptional activators (19, 20). Binding of retinoic acid to RAR initiates a cascade of biochemical events, leading to changes in cellular activities (21, 22). Each RAR binds to retinoic acid with a different affinity and is expressed disparately during differentiation and development (12, 23), suggesting that each RAR may have a specific and unique role in the regulation of these processes. Furthermore, the presence of various mRNA transcripts for each RAR (24, 25) leads to the postulate that isoforms of RAR proteins, encoded by these transcripts, may mediate distinct retinoic acid effects on cellular activities. These ideas are supported by the recent observations of lethality and/or multiple abnormalities at various stages of organogenesis in RAR mutant mice (12, 26).

The results of the current experiments demonstrated that under normal physiological conditions, the steady state level of mRNA transcripts for RAR{alpha} and -{gamma} in the prostate of adult rats was at least 20-fold higher than those in the seminal vesicles, kidney, and spleen. Although the relative abundance of RAR{alpha} mRNA in the prostate was comparable to that in the testis, the level of 3.4-kb RAR{gamma} mRNA was 20-fold higher than that in the testis. These results suggest that RAR{alpha} and -{gamma} may have important roles in prostate physiology. An increase in the level of RAR mRNA after castration and an acute suppression of RAR mRNA by testosterone in both the prostate and seminal vesicles of castrated animals demonstrate a down-regulation of RAR genes by testosterone in these two androgen-dependent organs. These results are consistent with our earlier observation of testosterone modulation of RAR{alpha} and -{gamma} mRNA transcripts in the testes of prepubertal rats (9) and suggest that retinoic acid/RAR-mediated processes may be involved in testosterone regulation of the prostate and seminal vesicles. However, the increment in RAR mRNA levels in the prostate after castration was 6- to 8-fold lower than that in the seminal vesicles. Furthermore, in castrated rats, the extent and pattern of acute effects of testosterone on RAR mRNA levels were also different between the prostate and seminal vesicle. As the same ligand-receptor pathway is involved in testosterone regulation of the prostate and seminal vesicles (5, 6, 27), and autoregulation of androgen receptors by androgen is also comparable in these two organs (27, 28), variations in the sensitivity of RAR genes to testosterone or in signal transduction pathways during postreceptor events may be responsible for the differences. Failure to obtain conclusive results in RARß mRNA levels, both under normal physiological condition and after castration, may be attributable to multiple factors. Among these is the loss of mRNA transcripts as the result of repeated washing, as all of the membranes have been hybridized with at least three different probes.

Previously, it was reported that mRNA transcripts of a number of renal proteins, including alcohol dehydrogenase, ornithine decarboxylase, ß-glucuronidase, and others, were up-regulated by androgen (6, 29, 30). Current observations of a decrease in levels of RAR{alpha} and -{gamma} mRNA in the kidney after castration and prevention of such a decrease by a physiological dose of exogenous testosterone suggest that the RAR genes in the kidney may also be up-regulated by androgen. The lack of a consistent increase in renal RAR{alpha} and -{gamma} mRNA levels in castrated rats after testosterone administration perhaps can be explained by a delayed response of renal cells to androgen, as an increase in mRNA levels for ornithine decarboxylase and S-adenosylmethionine decarboxylase in castrated rats and mice did not occur until at least 6–8 h after the administration of testosterone (29). It is worth noting that renal RAR mRNA levels also decreased acutely within 30 min after testosterone administration. Because the half-life of RAR mRNA transcripts was estimated to be approximately 1–2 h (31), the acute decrease in renal RAR mRNA levels as well as those in the prostate and seminal vesicles immediately after testosterone administration may have resulted from an increase in mRNA degradation. A decreased S-adenosylmethionine decarboxylase mRNA level preceding testosterone stimulation of the same gene has been noted in the kidney of castrated rats and mice (29). The following organ-specific changes in RAR mRNA levels may thus reflect differences in transcriptional regulation of RAR genes among organs. The up-regulation of renal RAR mRNAs by testosterone, as opposed to down-regulation of the same genes in the prostate and seminal vesicles, may contribute in part to their difference in androgen dependency.

The regulation of RAR mRNA expression has been examined in a number of tissues and cell types. In the testis, the steady state level of RAR mRNAs decreases during vitamin A deficiency, but can be stimulated by retinoic acid or retinol (32, 33, 34). In human hepatoma cells, mRNA transcripts for RARß were reported to be transcriptionally stimulated by retinoic acid, whereas RAR{alpha} mRNAs were not (35). In F-9 embryonic carcinoma cells, RARß mRNA transcripts were also reported to be stimulated by retinoic acid, but those of RAR{alpha} and -{gamma} did not respond to the same retinoic acid regimens (31, 36). In P-19 embryonic carcinoma cells, both RAR{alpha} and -ß mRNA transcripts were reported to be stimulated by retinoic acid, but with a different time course of effects (37, 38). The effects of retinoic acid on RARß mRNA transcripts are attributable to the activation of the RARß gene that contains the retinoic acid response element on the promoter region (39, 40). On the other hand, the level of mRNA transcripts for RAR{alpha}, -ß, and -{gamma} in F9 embryonic carcinoma cells was reported to be suppressed by cAMP and/or its analog, and the presence of retinoic acid was required for these effects (31, 36). It was postulated that activation of certain negative regulatory factors may be involved in the suppressive effects of cAMP (31). The presence of a cAMP-responsive element (CREß2) on the promoter region of the RARß gene and its involvement in the retinoic acid-dependent activation of the RARß2 promoter (41) support these ideas. Recent studies suggested that androgen may modulate prostate cell functions through a cAMP signal transduction pathway (42, 43), and early studies have demonstrated that androgen stimulated cAMP in rat seminal vesicle in vitro (44) and adenyl cyclase activity in the prostate of castrated rats (45). It is postulated that the cAMP pathway may also be involved in the androgen regulation of RAR expression in the prostate and seminal vesicles. Administration of exogenous testosterone to castrated rats might stimulate cellular cAMP, which, in turn, caused a decrease in RAR mRNA levels in the prostate and seminal vesicles. However, whether the cAMP-mediated pathway alone is accountable for the effects of testosterone on renal RAR mRNA remains debatable. Previously, Huang et al. (9) postulated that the testosterone stimulation of testicular RAR{alpha} mRNA in the prepubertal rat may reflect a balance between certain putative, but undefined, positive mechanisms and the negative effects of the cAMP pathway. Whether such a positive mechanism is also involved in the testosterone up-regulation of RAR mRNAs in the kidney remains to be verified experimentally.

In summary, the current study demonstrated the presence of a relatively high abundance of RAR mRNA transcripts in the prostate of adult rats under physiological conditions, and the expression of prostatic RAR mRNA can be modulated by testosterone. These findings and reports of metaplasia of prostate epithelial cells during vitamin A deficiency (46), prevention of prostate carcinogenesis by retinoic acid and its analogs (47, 48), and retinoic acid inhibition of the androgen regulation of cell proliferation in seminal vesicles of neonatal mice (49) emphasize the importance of the retinoic acid/RAR pathway in the effects of androgen on prostate physiology and pathophysiology. Further identification of the mechanisms or factors involved in this regulation may facilitate our understanding of the pathogenesis, and perhaps its prevention, of prostate cancer and benign prostatic hyperplasia.


   Acknowledgments
 
We thank Prof. P. Chambon for his generous gift of RAR cDNAs, and Dr. Richard Watson for critical review and suggestion in the preparation of the manuscript.


   Footnotes
 
1 This work was supported in part by the C. R. Bard Endowed Fund. Back

2 Current address: Huashang Hospital, Shanghai, People’s Republic of China. Back

Received June 7, 1996.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Coffey DS 1988 Androgen action and the sex accessory tissues. In: Knobil E, Neill JD (eds) The Physiology of Reproduction. Raven Press, New York, pp 1081–1119
  2. Cunha GR, Donjacour AA, Cooke PS, Mee S, Bigsby RM, Higgins SJ, Sugimura Y 1987 The endocrinology and developmental biology of the prostate. Endocr Rev 8:338–362[Abstract/Free Full Text]
  3. Kyprianou N, Isaacs JT 1988 Activation of programmed cell death in the rat ventral prostate after castration. Endocrinology 122:552–562[Abstract/Free Full Text]
  4. Lee C, Sensibar JA, Dudek SM, Hipakka RA, Liao S 1990 Prostatic ductal system in rats: regional variation in morphological and functional activities. Biol Reprod 43:1079–1086[Abstract]
  5. Catterall JF, Kontula KK, Watson CS, Seppanen PJ, Funkenstein B, Melanitou E, Hickok NJ, Bardin CW, Janne OA 1986 Regulation of gene expression by androgens in murine kidney. Recent Prog Horm Res 42:71–109
  6. Isomaa V, Pajunen AEI, Bardin CW, Janne OA 1982 Nuclear androgen receptors in the mouse kidney: validation of a new assay. Endocrinology 111:833–843[Abstract/Free Full Text]
  7. Mooradian AO, Morley JE, Korenman SG 1987 Biological actions of androgens. Endocr Rev 8:1–28[Abstract/Free Full Text]
  8. O’Malley BW, Tsai MJ 1992 Molecular pathways of steroid receptor action. Biol Reprod 46:163–167[Abstract]
  9. Huang HFS, Li MT, Pogach LM, Qian L 1994 Messenger ribonucleic acid of rat testicular retinoic acid receptors: developmental pattern, cellular distribution and testosterone effect. Biol Reprod 51:541–550[Abstract]
  10. De Luca LM 1991 Retinoids and their receptors in differentiation, embryogenesis and neoplasia. FASEB J 5:2924–2933[Abstract]
  11. Summerbell D, Maden M 1990 Retinoic acid, a developmental signalling molecule. Trends Neurosci 13:142–147[CrossRef][Medline]
  12. Mendelsohn C, Lohnes D, Decimo D, Lufkin T, LeMeur M, Chambon P, Mark M 1994 Function of the retinoic acid receptors (RARs) during development. II. Multiple abnormalities at various stages of organogenesis in RAR double mutants. Development 120:2749–2771[Abstract]
  13. Chomczynski P, Sacchi N 1987 Single step method of mRNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162:156–159[Medline]
  14. Aviv H, Leder P 1972 Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid cellulose. Proc Natl Acad Sci USA 69:1408–1412[Abstract/Free Full Text]
  15. Sambrook J, Fritsch EF, Maniatis T 1989 Molecular Cloning–A Laboratory Manual. Cold Spring Harbor Laboratory, Cold Spring Harbor
  16. Zelent A, Krust A, Petkovich M, Kastner P, Chambon P 1989 Cloning of murine {alpha} and ß retinoic acid receptors and a novel receptor predominatly expressed in skin. Nature 339:714–717[CrossRef][Medline]
  17. Krust A, Kastner P, Petkovich M, Zelent A, Chambon P 1989 A third human retinoic acid receptor, h-RAR-{gamma}. Proc Natl Acad Sci USA 86:5310–5314[Abstract/Free Full Text]
  18. Huang HFS, Boccabella AV 1988 Dissociation of the quantitative and qualititative effects of the suppression of testicular testosterone upon spermatogenesis. Acta Endocrinol (Copenh) 118:209–217[Abstract/Free Full Text]
  19. Evans RM 1988 The steroid and thyroid hormone receptor super family. Science 240:889–895[Abstract/Free Full Text]
  20. Mangelsdorf DJ, Kliewer SA, Kakizuka A, Umesono K, Evans RM 1993 Retinoid receptors. Recent Prog Horm Res 48:99–121
  21. Chambon P 1995 The molecular and genetic dissection of the retinoid signal pathway. Recent Prog Horm Res 50:317–332
  22. Petkovich M 1992 Regulation of gene expression by vitamin A: the role of nuclear retinoic acid receptors. Annu Rev Nutr 12:443–471[CrossRef][Medline]
  23. Zelent A, Mendelsohn C, Kastner P, Krust A, Garnier JM, Ruffenach F, Leroy P, Chambon P 1991 Differentially expressed isoforms of the mouse retinoic acid receptor b are generated by usage of two promoters and alternative splicing. EMBO J 10:71–81[Medline]
  24. Leroy P, Krust A, Zelent A, Mendelsohn C, Garnier JM, Kastner P, Dierich A, Chambon P 1991 Multiforms of the mouse retinoic acid receptor alpha are generated by alternative splicing and differential induction by retionic aicd. EMBO J 10:59–69[Medline]
  25. Kastner P, Krust A, Mendelsohn C, Garnier JM, Zelent A, Leroy P, Staub A, Chambon P 1990 Murine isoforms of retinoic acid receptor {gamma} with specific patterns of expression. Proc Natl Acad Sci USA 87:2700–2704[Abstract/Free Full Text]
  26. Lufkin T, Lohnes D, Mark M, Dierich A, Gorry P, Gaub M-P, Lemeur M, Chambon P 1993 High postnatal lethality and testis degeneration in retinoic acid receptor {alpha} mutant mice. Proc Natl Acad Sci USA 90:7225–7229[Abstract/Free Full Text]
  27. Shan LX, Rodriguez MC, Janne OA 1990 Regulation of androgen receptor protein and mRNA concentrations by androgens in rat ventral prostate and seminal vesicles and in human hepatoma cells. Mol Endocrinol 4:1636–1646[Abstract/Free Full Text]
  28. Tan JA, Joseph DR, Quarmby VE, Lubahn DB, Sar M, French FS, Wilson EM 1989 The rat androgen receptor: primary structure, autoregulation of its messenger ribonucleic acid, and immunocytochemical localization of the receptor protein. Mol Endocrinol 12:1276–1285
  29. Crozat A, Palvimo JJ, Julkunen M, Janne OA 1992 Comparison of androgen regulation of ornithine decarboxylase and S-adenosylmethionine decarboxylase gene expression in rodent kidney and accessory sex organs. Endocrinology 130:1131–1144[Abstract/Free Full Text]
  30. Ohno S, Stenius C, Christian L, Harris C, Ivey C 1970 More about the testosterone induction of kidney alcohol dehydrogenase activity in the mouse. Biochem Genet 4:565–577[CrossRef][Medline]
  31. Hu L, Gudas LJ 1990 Cyclic AMP analogs and retinoic acid influence the expression of retinoic acid receptor {alpha}, ß and {gamma} mRNAs in F9 teratocarcinoma cells. Mol Cell Biol 10:391–396[Abstract/Free Full Text]
  32. Kim KH, Griswold MD 1990 The regulation of retinoic acid receptor mRNA levels during spermatogenesis. Mol Endocrinol 4:1679–1688[Abstract/Free Full Text]
  33. Haq R, Pfahl M, Chytil F 1991 Retinoic acid affects the expression of nuclear retinoic acid receptors in tissues of retinol deficient rats. Proc Natl Acad Sci USA 88:8272–8276[Abstract/Free Full Text]
  34. Van Pelt AMM, Van der Brink CE, De Rooij DJ, Van der Saag PT 1992 Changes in retinoic acid receptor messenger ribonucleic acid levels in the vitamin A deficient rat testis after administration of retinoids. Endocrinology 131:344–350[Abstract/Free Full Text]
  35. de The H, Marchio A, Tiollais P, Dejean A 1989 Differential expression and ligand regulation of the retinoic acid receptor {alpha} and ß genes. EMBO J 8:429–433[Medline]
  36. Martin CA, Ziegler LM, Napoli JL 1990 Retinoic acid, dibutyryl-cAMP, and differentiation affect the expression of retinoic acid receptors in F9 cells. Proc Natl Acad Sci USA 87:4804–4808[Abstract/Free Full Text]
  37. Song S, Siu CH 1989 Retinoic acid regulation of the expression of retinoic acid receptors in wild-type and mutant embryonal carcinoma cells. FEBS Lett 256:51–54[CrossRef][Medline]
  38. Kruyt FAE, van der Brink CE, Defize LHK, Donath MJ, Kastner P, Kruijer W, Chambon P, van der Saag PT 1991 Transcriptional regulation of retinoic acid receptor ß in retinoic acid sensitive and resistant P 19 embryocarcinoma cells. Mech Dev 33:171–178[CrossRef][Medline]
  39. de The H, Vivanco-Ruiz MM, Tiollais P, Stunnenberg H, Dejean A 1990 Identification of a retinoic acid responsive element in the retinoic acid receptor ß gene. Nature 343:177–180[CrossRef][Medline]
  40. Hoffmann B, Lehmann JM, Zhang XK, Herrmann T, Husmann M, Graupner G, Pfahl M 1990 A retinoic acid receptor-specific element controls the retinoic acid receptor-beta promoter. Mol Endocrinol 4:1727–1736[Abstract/Free Full Text]
  41. Kruyt FAE, Folkers G, van der Brink CE, van der Saag PT 1992 A cyclic AMP response element is involved in retinoic acid-dependent RARß2 promoter activation. Nucleic Acids Res 20:6393–6399[Abstract/Free Full Text]
  42. Nakhla AM, Kahn MS, Rosner W 1990 Biologically active steroids activate receptor- bound human sex hormone-binding globulin to cause LNCaP cells to accumulate adenosine 3',5'-monophosphate. J Clin Endocrinol Metab 71:398–404[Abstract/Free Full Text]
  43. Rosner W, Hryb DJ, Khan MS, Nakhla AM, Romas NA 1992 Sex hormone-binding globulin binding to cell membranes and generation of a second messenger. J Androl 13:101–106[Free Full Text]
  44. Thomas JA, Singhal RL 1973 Testosterone-stimulation of adenyl cyclase and cyclic 3'5' adenosine monophosphate-3H formation in rat seminal vesicles. Biochem Pharmacol 22:507–511[CrossRef][Medline]
  45. Singhal RL, Parulekar MR, Vijayvargiya R, Robison GA 1971 Metabolic control mechanism in mammalian systems: involvement of adenosine 3',5' cyclic monophosphate in androgen action. Biochem J 125:329–342[Medline]
  46. Wolbach S, Howe PR 1925 Tissue changes following deprivation of fat soluble A vitamin. J Exp Med 42:753–777[Abstract]
  47. Pollard M, Luckert PH, Sporn MB 1991 Prevention of primary prostate cancer in Lobund Wistar rats by N-(4-hydroxyphenyl retinamide). Cancer Res 51:3610–3611[Abstract/Free Full Text]
  48. Lasnitzki I 1955 The influence of a hypervitaminosis on the effect of 20-methylcholanthrene on mouse prostate gland grown in vitro. Br J Cancer 9:434–441[Medline]
  49. Tanji N, Yokoyama M, Takeuchi M, Terada N, Dahiya R, Cunha G 1996 Inhibitory effects of retinoic acids on androgen-dependent development of neonatal mouse seminal vesicles in vitro. Endocrinology 137:2887–2895[Abstract]



This article has been cited by other articles:


Home page
 J AndrolHome page
F. Richter, A. Joyce, F. Fromowitz, S. Wang, J. Watson, R. Watson, R. J. Irwin Jr, and H. F. S. Huang
Immunohistochemical Localization of the Retinoic Acid Receptors in Human Prostate
J Androl, November 1, 2002; 23(6): 830 - 838.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. S. Prins, W. Y. Chang, Y. Wang, and R. B. van Breemen
Retinoic Acid Receptors and Retinoids Are Up-Regulated in the Developing and Adult Rat Prostate by Neonatal Estrogen Exposure
Endocrinology, September 1, 2002; 143(9): 3628 - 3640.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. F. S. Huang, M.-T. Li, W. Giglio, R. Anesetti, J. E. Ottenweller, and L. M. Pogach
The Detrimental Effects of Spinal Cord Injury on Spermatogenesis in the Rat Is Partially Reversed by Testosterone, but Enhanced by Follicle- Stimulating Hormone
Endocrinology, March 1, 1999; 140(3): 1349 - 1355.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
J. Su, X. Chai, B. Kahn, and J. L. Napoli
cDNA Cloning, Tissue Distribution, and Substrate Characteristics of a cis-Retinol/3alpha -Hydroxysterol Short-chain Dehydrogenase Isozyme
J. Biol. Chem., July 10, 1998; 273(28): 17910 - 17916.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Chai, Y. Zhai, and J. L. Napoli
cDNA Cloning and Characterization of a cis-Retinol/3alpha -Hydroxysterol Short-chain Dehydrogenase
J. Biol. Chem., December 26, 1997; 272(52): 33125 - 33131.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Huang, H. F. S.
Right arrow Articles by Irwin, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huang, H. F. S.
Right arrow Articles by Irwin, R. J.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals