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Effect of androgen deprivation on penile ultrastructure

Zhou-Jun SHEN1, Xie-Lai ZHOU1, Ying-Li LU2, Zhao-Dian CHEN1

1Department of Urology, First Affiliated Hospital, 2Department of Endocrinology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University , Hangzhou 310003, China

Asian J Androl 2003 Mar; 5: 33-36             


Keywords: corpus cavernosum; tunica albuginea; androgens; penis; scanning electron microscopy
Abstract

Aim: To investigate the ultrastructural changes of penile corpus cavernosum and tunica albuginea in rats treated with castration or finasteride. Methods: Eighteen male Sprague-Dawley rats of nine weeks old were randomly divided into three groups with 6 rats each. Group A served as the control, Group B was castrated and Group C, treated with finasteride. Four weeks later, rats were anesthetized and blood samples obtained for the determination of serum testosterone (T) and dihydrotestosterone (DHT) levels; penile tissues were taken for scanning electron microscopy. Results: The T, free T and DHT levels in Group B and the DHT level in Group C were significantly lower than those in Group A (P<0.05). The tunica albuginea was significantly thinner in Group B than that in Group A (P<0.05), but there was no significant difference between Group C and Group A (P>0.05). Elastic fibers in the tunica albuginea of Group A were very rich and arranged regularly and undulatedly, but in Group B, most of the elastic fibers were replaced by collagenous fibers. In Group C, the tunica albuginea was mainly composed of thick and irregular-arranged collagenous fibers. In Group A, there were abundant smooth muscle fibers in the trabeculae of corpus cavernosum, but they were much less in Group C and scarce or even disappeared in Group B. In Groups B and C, the diminished/disappeared smooth muscle fibers were replaced by irregularly arranged collagenous fibers. Conclusion: In rats, androgen is essential for maintaining the normal structure of penile tunica albuginea and corpus carvenosum.

1 Introduction

Androgen is vital for the development of external genitalia in male mammals. In adult males, androgen is essential for the expression of normal libido, but seems to be not indispensable to the erectile activity [1]. We indicated that the serum testosterone (T) and free testosterone (FT) levels were significantly lower, the tunica albuginea much thinner and the penile corpus cavernosum contained less smooth muscles and more collagenous fibers in the elderly rats than in the young and middle-aged rats [2, 3]. Zhang et al [4] pointed out that castration induced apoptosis of penile corpus cavernosum in mature rats, which was prevented by T supplementation. This work suggested that the changes in androgen level might affect the morphology of the penile corpus caver-nosum, but the effect of androgen deprivation on the ultrastructure of the erectile tissue was not available so far in the literature. The present study was designed to elucidate this point in rats.

2 Materials and methods

2.1 Animals and treatment

Eighteen male Sprague-Dawley rats, 9 week old with body weight of 34545 g, were purchased from the Experimental Animal Center of this University. They were randomly divided into three groups with six rats each and were maintained in a 12 h light/12 h dark animal room with free access to food and tap water. Group A served as the control, Group B was castrated and Group C, gavaged with finasteride at a dose of 4.5 mg.kg-1.day-1. Four weeks later, rats were killed by intraperitoneal injection of ketamine and phenobarbital sodium and blood samples were obtained for the determination of serum total and free testosterone (T & FT) and dihydrotest-osterone (DHT) levels with radioimmunoassay; penile tissues (tunica albuginea and corpus cavernosum) were taken from similar site for scanning electron microscopy.

2.2 Scanning electron microscopy

The penile tissues were washed with physiological saline, fixed in 2.5 % glutaraldehyde (pH 7.2~7.4) and washed three times in 0.1 mol/L phosphate buffer saline (PBS). The samples were then post-fixed in 1 % osmium tetroxide for 2 h, dehydrated in graded ethanol solutions and dried by the critical point drying method. The dried samples were then mounted on suitable carriers, coated with gold and examined under a scanning electron microscope (Leica-Stereoscan 260,UK).

2.3 Statistical analysis

Data were expressed in meanSD and processed with statistical package of SPSS 10.0. Analysis of variance was performed with the t-test. Significance of difference was set at P<0.05.

3 Results

3.1 Androgen level

The serum concentrations of T, FT and DHT are shown in Table 1. The T, FT and DHT levels in Group B and the DHT level in Group C were significantly lower than those in Group A (P<0.05). There were no significant differences in the T and FT levels between Groups A and C (P>0.05).

Table 1. Serum T, FT and DHT levels. bP<0.05, compared with controls.

Group

n

T (nmol/L)

FT (pmol/L)

DHT (pg/mL)

A (control)

6

13.9510.89

43.9125.85

106.257.3

B (castrated)

6

0.790.51b

1.830.15b

48.48.6b

C (finasteride)

6

11.035.68

47.3332.45

47.116.5b

3.2 Ultrastructure of tunica albuginea

The thickness of tunica albuginea was listed in Table 2. It was significantly thinner in Group B than in Group A (P<0.05), but there was no significant difference between Groups C and A (P>0.05). In Group A (Figure 1), the elastic fibers in tunica albuginea were very rich and arranged regularly and undulatedly, while in Group B (Figure 2), the elastic fibers were mostly replaced by collagenous fibers. In Group C (Figure 3), the regularly-arranged elastic fibers were not seen and replaced by thick and irregularly-arranged collagenous fibers.

Table 2. Thickness of tunica albuginea (meanSD). bP<0.05, compared with control.

Group

n

Thickness (mm)

A (control)

6

0.160.03

B (castrated)

6

0.040.01b

C (finasteride)

6

0.140.03

Figure 1. Ultrastructures of tunica albuginea, Group A. (300)

Figure 2. Ultrastructures of tunica albuginea, Group B. (300)

Figure 3. Ultrastructures of tunica albuginea, Group C. (300)

3.3 Ultrastructure of corpus cavernosum

In Group A (Figure 4a & b), the smooth muscle fibers in the trabeculae were rich and contained a few elastic and collagenous fibers. Structure of the sinusoids was perfect and clear.

Figure 4a & b. Ultrastructures of corpus cavernosum, Group A. (a300, b900)

In Group B (Figure 5a & b), the corpus cavernosum was mainly composed of a large amount of collagenous fibers, which were thick and irregularly arranged. Smooth muscle fibers in the trabeculae were diminished or completely disappeared. The sinusoids were markedly depressed and narrowed.

Figure 5a & b. Ultrastructures of corpus cavernosum, Group B. (a300, b900)

In Group C (Figure 6a & b), the corpus cavernosum also contained a considerable amount of thick and irregularly-arranged collagenous fibers, but the degree of fibrosis was not so marked as in Group B and the types of fibrosis were different between these two groups. The sinusoids of Group C were partially depressed, but the structure of the sinusoids was still retained.

Figure 6a & b. Ultrastructures of corpus cavernosum, Group C. (a300, b900)

4 Discussion

The present study showed that in the castration animals, there were a high degree of fibrosis in the corpus cavernosum with irregularly arranged collagenous fibers and a marked decrease in smooth muscle fibers, while in the DHT-inhibited group, the corpus cavernosum contained quite an amount of thick and irregular-arranged collagenous fibers, but the degree of fibrosis was lower than that in the castration group. Results suggest that androgen is essential for the maintenance of normal ultrastructure of corpus cavernosum. Zhang et al [4] demonstrated that in mature rats, castration induced apoptosis in corpus cavernosum with the replacement of the apoptotic tissues by fibrous tissue. This may be one of the pathways through which androgen deprivation acts on corpus cavernosum. In the present study, the degree and type of corpus cavernosum fibrosis in the two groups were different, suggesting that T and DHT act on the corporal cavernosal tissues independently and differently. Finasteride can only inhibit the action of DHT, but not T on the corporal cavernosal tissue, therefore, the degree of fibrosis was less in the DHT-inhibited group than in the castration group.

The tunica albuginea of penis plays a major role in the erection mechanism. It compresses the subalbugineal venules, thus decreasing the venous outflow during erection and provides an inextensible fibrous frame for the erectile tissue of the penis [5]. In the normal control group of this study, the elastic fibers in the tunica albuginea were very rich and arranged regularly and undulatedly. In the castration group, the thickness of tunica albuginea decreased significantly and the elastic fibers were mostly replaced by collagenous fibers and in the DHT-inhibited group, the elastic fibers were replaced by disorganized and thick collagenous fibers. These results indicate that androgen is also essential for the maintenance of the normal structures of tunica albuginea.

It can be concluded that androgen is indispensable to the maintenance of normal ultrastructures of the erectile tissues. However, the interrelationship between androgen and the structure and function of the erectile tissue is not quite clear and sometimes even controversial, and further investigation is needed.

References

[1] Luisi M, Franchi F. Double-blind group comparative study of testosterone undecanoate and testosterone in hypogo-nadal male patients. J Endocr Invest 1980; 3: 305-8.
[2] Shen ZJ, Lu YL, Chen ZD, Chen F, Chen Z. Effects of androgen and aging on gene expression of vasoactive intestinal polypeptide in rat corpus cavernosum. BJU Int 2000; 86: 133-7.
[3] Shen ZJ, Jin XD, Chen ZD, Shi YH. Effect of aging on penile ultrastructure. Asian J Androl 2001; 3: 281-4.
[4] Zhang XH, Hu LQ, Zheng XM, Li SW. Apoptosis in rat erectile tissue induced by castration. Asian J Androl 1999; 1:181-5.
[5] Goldstein AM, Padma-Nathan H. The microarchitecture of the intracavenous smooth muscle and the cavernous fibrous skeleton. J Urol 1990; 144: 1144-6.

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Correspondence to: Dr. Zhou-Jun SHEN, Professor, Department of Urology, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
Tel: +86-571-8723 6833, Fax: +86-571-8723 6628
E-mail: shenzhj@mail.hz.zj.cn
Received 2002-09-02      Accepted 2003-02-14