Effect of long-term hyperprolactinemia on the prolactin receptor content of the rat ventral prostate

The rat ventral prostate contains prolactin receptors, and during sexual maturation prolactin stimulates the growth of this gland. The aim of the present investigation was to evaluate whether prolactin is involved in the regulation of the number of its own receptor sites in the rat ventral prostate. To this end, the content of prolactin receptors was estimated in prostate membranes of control and chronically hyperprolactinemic rats both before and after in vitro desaturation with 4 M MgCl2. Hyperprolactinemia resulted in a 40% increase in the number of available prolactin receptors (P less than 0.05). In vitro desaturation of receptors resulted in loss of 84% of protein and 36 +/- 6% and 52 +/- 6% of prolactin receptors from ventral prostate membranes of control and hyperprolactinemic rats respectively (P less than 0.05). We have concluded that the rat ventral prostate membranes are not suited to in vitro desaturation of prolactin receptors with MgCl2. From the increase in the number of available prolactin receptors after hyperprolactinemia we have concluded that prolactin is involved in the regulation of the number of its own receptors in the rat ventral prostate.     

Effect of androgen deprivation on the expression of aquaporins in rat prostate and seminal vesicles

The aim of this study was to investigate the level of secretions of prostate and seminal vesicles and its association with the expression of AQP0, 1, 4, 5, 6 and 8 in castrated rats. Eight‐week‐old male Sprague‐Dawley (SD) rats (n = 18) were randomly divided into control group, castrated rats group and castrated followed testosterone replacement group. Four weeks after surgery, the secretions and expression of AQP0, 1, 4, 5, 6 and 8 of prostate and seminal vesicles were determined. Serum testosterone was significantly lower in castrated groups than in control and testosterone replacement groups (P < 0.05). The level of prostate and seminal vesicle secretions and the expressions of AQP0, 1, 4, 5, 6 and 8 in prostate and seminal vesicles were significantly lower in castrated group than in control and castrated followed testosterone replacement groups (P < 0.05). The decreased prostatic and seminal vesicle secretions in castrated rats may be related to the decrease in AQP0, 1, 4, 5, 6 and 8 in prostatic tissue and seminal vesicles.     

Modulation of ornithine decarboxylase activity by prolactin in seminal vesicles of the rat

The stimulatory effect of prolactin on sexual accessory glands is well established, though the mechanism of trophic action remains poorly understood. We have therefore assessed the effect of high levels of prolactin on ornithine decarboxylase activity and polyamine content in seminal vesicles (SV) of adult rats. Hyperprolactinaemia was induced by implantation of tissue fragments of a prolactin-secreting tumour 7315a, and the rats killed at 35 days post-inoculation. Serum levels of prolactin were increased significantly ( p <0.001) in tumour-bearing rats. Levels of testosterone in serum were reduced markedly, whereas LH levels remained unchanged. SV weight in the experimental group was not significantly different from that in the corresponding control group. A clear increase in ornithine decarboxylase activity of SV was observed ( p <0.001) in the hyperprolactinaemic rats. However, there was no change in the polyamine content of SV in tumour-bearing rats, compared to the control group. These results indicate that ornithine decarboxylase activity in SV of adult rats is regulated mainly by prolactin. This experimental model may be useful for identification of some of the events involved in the trophic action of prolactin.     

Effect of nitrofurazone on the reproductive organs in adult male mice

Aim: To study the effect of 5-nitro-2-furaldehyde semicarbazone (nitrofurazone), a derivative of nitrofuran, on male reproductive organs of Parkes (P) strain mice. Methods: Mice were given nitrofurazone orally at a dose of 64mg/kg body weight per day, for 10 and 20 days, and were killed 24 h and/or 56 days after the last treatment. Histological appearance of testis, motility and number of spermatozoa in cauda epididymidis, and biochemical indices in epididymis and seminal vesicle were evaluated. Results: Histologically, testis showed marked regressive changes in the seminiferous tubules in mice treated with nitrofurazone. Ten days after treatment, there was much depletion of germ cells in the seminiferous tubules, and the germinal epithelium was lined mainly with Sertoli cells, spermatogonia, spermatocytes, and a few round spermatids; intraepithelial vacuoles and multinucleated giant cells were also observed in tubules. By 20 days, regressive changes in the seminiferous tubules were further pronounced, and pachytene spennatocytes were the most advanced germ cells noticed in the tubules. In severe cases, the tubules were lined with a thin layer of Sertoli cells and spermatogonia. The treatment also caused marked reductions in the motility and number of spermatozoa in the cauda epididymidis, in weight and the level of fructose in the seminal vesicle, and in sialic acid level in the epididymis. Fifty six days after drug withdrawal, the alterations induced in the reproductive organs returned to control levels. Conclusion: Our results suggest that nitrofurazone treatment in P mice induces marked alterations in the male reproductive organs, and that the alterations are reversible following cessation of treatment.     

Opposite effects of unmodified prolactin and a molecular mimic of phosphorylated prolactin on morphology and the expression of prostate specific genes in the normal rat prostate

BACKGROUND: In the current study, we have investigated the individual roles of unmodified, wild-type prolactin (WT PRL) and a molecular mimic of phosphorylated prolactin (S179D PRL) in the normal rat prostate. METHODS: In the first animal experiment, recombinant WT PRL and S179D PRL were delivered to adult male rats at a rate of 14 microg/kg per day for 3 weeks. In the second animal experiment, two subcutaneous (200 microg/kg) injections of long-acting forms of the two PRLs were given to adult male rats on day 1 and day 22 for a total of 5.5 weeks of treatment. RESULTS: The different forms of PRL had opposite effects on the normal rat prostate, independently of androgens. WT PRL promoted morphologic changes in prostate epithelium consistent with preparation for cell proliferation, whereas S179D PRL produced morphologic evidence of a more differentiated epithelium. Northern blot analysis of expression of the two major prostate specific proteins, prostatein and probasin, showed that WT PRL decreased, whereas S179D PRL increased, the expression of the mRNAs for these two proteins. At the same time, S179D PRL reduced both testosterone and dihydrotestosterone levels. CONCLUSION: We conclude that PRL is an important modulator of normal rat prostate biology and that different forms of PRL have specific functions. The molecular mimic of phosphorylated PRL, S179D PRL, is the most important in terms of epithelial cell differentiation.     

Antiandrogenic activities of Glycyrrhiza glabra in male rats

Abnormal levels of androgens cause many diseases like benign prostatic hyperplasia and hormone dependent cancers. Although the reduction in serum testosterone (T) by Glycyrrhiza glabra has been reported, its effects on seminal vesicle (SV) and prostate tissues have never been reported. This study was carried out to investigate different aspects of antiandrogenic properties of this plant. Immature male rats were divided into five groups ( n  = 7): castrated rats without any treatment received only vehicle; castrated rats plus T replacement; three castrated groups with T replacement plus various doses of G. glabra extract (75, 150 and 300 mg/kg). All of the injections were carried out once daily in subcutaneous manner for 7 days. On the eighth day, blood samples were collected for total T measurement. Ventral prostate (VP), SV and levator ani muscle were dissected and weighed. Slides prepared from prostate were assessed histologically. The variation in the relative and absolute volume of the prostate tissue compartments was determined. Those receiving the doses of 150 and 300 mg/kg showed a significant reduction ( p  <   0.05) in prostate weight, total T and VP epithelium/stroma ratio (V/V). These results in SV and levator ani were shown in response to 300 mg/kg of extract. Increasing in T metabolism, down-regulation of androgen receptors or activation of oestrogen receptors could be involved mechanisms. This study showed that alcoholic extract of G. glabra has antiandrogenic properties.     

Dose-dependent induction of ornithine decarboxylase and S-adenosyl-methionine decarboxylase activity by testosterone in the accessory sex organs of male rats.

The dose-dependent induction of ornithine decarboxylase (ODC) and adenosylmethionine decarboxylase (AMDC) activity in the different lobes of the prostate and the seminal vesicles (SV), 24 hours after administration of testosterone to castrated Wistar rats, has been studied. ODC and AMDC activities were low in all lobes 10 days after castration. A dose of approximately 300 micrograms testosterone/100 g body weight (B.W.) gave an ODC activity of 50 percent of maximum response, and at 600 micrograms/100 g B.W. maximum activity was reached in all the prostatic lobes and the SV. In the lateral and dorsal prostate, and the coagulating gland, the dose of testosterone giving 50% of maximum AMDC activity was reached after administration of between 450 and 600 micrograms/100 g B.W. In the ventral prostate and SV, the dose giving a 50% response was approximately 700 micrograms/100 g B.W. In conclusion, all prostatic lobes showed a clear dose-response relationship concerning the activity of ODC and AMDC following administration of different doses of testosterone. We have found minor differences in androgen responsiveness between the lobes when looking at the dose requirements for induction of AMDC activity. The dose-response curves could possibly be useful as a rapid in vivo bioassay for compounds with anti-androgenic properties in the prostate.     

Effects of androgens, prolactin and bromocriptine on seminal vesicular enzymes of the pyruvate malate cycle involved in lipogenesis in castrated mature monkeys, Macaca radiata

The interaction of androgens and prolactin, the major factors regulating the male accessory sex organs, on the specific activity of seminal vesicular enzymes of the pyruvate/malate cycle were studied in castrated mature monkeys. Castration decreased the activity of these enzymes, including NADP+ isocitrate dehydrogenase, ATP citrate lyase, malate dehydrogenase, malic enzyme and fatty acid synthase. Testosterone propionate (TP)/dihydrotestosterone given as replacement to castrates increased the activity of all these enzymes, except for malate dehydrogenase. Prolactin restored normal activity of ATP citrate lyase, malic enzyme and fatty acid synthase but not of isocitrate dehydrogenase and malate dehydrogenase (MDH). Prolactin had a specific control over MDH. Moreover, when prolactin was combined with androgens a further stimulatory influence was observed on fatty acid synthase activity. In order to prove the direct influence of prolactin on enzymes of the pyruvate/malate cycle, bromocriptine was administered and this inhibited all of the enzymes. Thus prolactin was found to have a direct, as well as a synergistic, action with androgens on enzymes of the pyruvate/malate cycle in the seminal vesicles of monkeys.     

Stimulating effects of quercetin on sperm quality and reproductive organs in adult male rats

Aim： To investigate effects of quercetin on weight and histology of testis and accessory sex organs and on sperm quality in adult male rats. Methods： Male Sprague-Dawley rats were injected s.c. with quercetin at the dose of 0, 30, 90, or 270 mg/kg body weight/day （hereafter abbreviated Q0, Q30, Q90 and Q270, respectively）, and each dose was administered for treatment durations of 3, 7 and 14 days. Results： From our study, it was found that the effects of quercetin on reproductive organs and sperm quality depended on the dose and duration of treatment. After Q270 treatment for 14 days, the weights of testes, epididymis and vas deferens were significantly increased, whereas the weights of seminal vesicle and prostate gland were significantly decreased, compared with those of Q0. The histological alteration of those organs was observed after Q270 treatment for 7 days as well as 14 days. The sperm motility, viability and concentration were significantly increased after Q90 and Q270 injections after both of 7 and 14 days. Changes in sperm quality were earlier and greater than those in sex organ histology and weight, respectively. Conclusion： Overall results indicate that quercetin might indirectly affect sperm quality through the stimulation of the sex organs, both at the cellular and organ levels, depending on the dose and the duration of treatment. Therefore, the use of quercetin as an alternative drug for treatment of male infertility should be considered. （Asian J Androl 2008 Mar. 10： 249-258）     

The use of steroid-containing silastic implants in male nude mice: Plasma hormone levels and the effect of implantation on the weights of the ventral prostate and seminal vesicles

The effects of implantation of steroid-containing capsules into male nude mice on steroid concentrations in plasma and weight of accessory sex organs were studied. Intact male nude mice had plasma levels of testosterone (T) of 8.0 ± 2.4 ng/ml, while T implantation (length 1.0 cm) of a group with castrated male mice resulted in a mean level of 8.1 ± 0.3 ng/ml. This level was reached within 2 days after implantation and lasted for at least 40 days. After longer periods of application (up to 75 days) physiological levels could still be attained. Treatment of intact male nude mice with estradiol (E2)-containing implants (length 0.5 cm) resulted in constant levels of plasma-E2 (250 pg/ml) also lasting for at least 32 days. This treatment resulted in a mean plasma-T level of 1.0 ± 0.2 ng/ml, which was still significantly higher than that obtained after castration (0.14 ± 0.03 ng/ml). Up to 16 days after implantation E2 did not cause a decrease of the weights of the accessory sex glands in intact male mice, while after 32 days a significant reduction (50% of the control animals) of the organ weights was observed. The present data obtained with T and E2 implantation show that this route of administration of hormones is also very applicable in the nude mouse model.     

Stimulation of ornithine decarboxylase in the rat prostate by seminal plasma inhibin

The effect of seminal plasma inhibin on ornithine decarboxylase activity (ODC) in the rat prostate was studied. A single bolus injection of seminal plasma inhibin caused a 3- to 4-fold increase in ODC activity within 2 h whereas testicular ODC was unchanged. The ODC response to seminal plasma inhibin was neutralized by specific antibodies generated against the inhibin preparation. Another peptide, thyroid releasing hormone has no effect on prostatic ODC activity, but it blocked the increase in enzyme activity induced by treatment with seminal plasma inhibin.     

Localization of lactoferrin in the male reproductive tract

The immunohistochemical localization of lactoferrin in the normal human prostate, seminal vesicle, vas deferens, epididymis and testis was studied using the peroxidase-antiperoxidase method at the light and electron microscopical level. Lactoferrin immunoreactivity was localized in the glandular epithelial cells and granulocytes in the prostate and seminal vesicle. In the prostate, lactoferrin showed an uneven distribution; some of the glands contained exclusively positive cells and others were completely lactoferrin negative, while the rest contained scattered positive cells. The seminal vesicles were divided into three segments, and their lactoferrin content varied significantly although it was always epithelial. The ductus deferens, epididymis and testis contained no lactoferrin. In conclusion, lactoferrin was found in the prostate and seminal vesicles, but not in the testis.     

Possible involvement of the accessory sex glands in the regulation of pituitary hormones

A time-course alteration in the blood levels of gonadotrophin was evaluated in male rats aged 49 days after: (a) removal of the seminal vesicles, (b) bilateral orchidectomy, or (c) bilateral orchidectomy together with removal of the seminal vesicles. Age-matched sham-operated animals served as controls. Removal of the seminal vesicles resulted in elevation in the blood levels of LH, FSH and prolactin compared to controls. As expected, bilateral orchidectomy also resulted in the elevation of serum gonadotrophins. In the absence of both the seminal vesicles and the testes, LH and FSH levels were increased further compared to orchidectomy alone. Thus the present study suggests the presence of a feedback mechanism between the seminal vesicles and pituitary which is more pronounced in the absence of the testes.     

Seminal fluid from men with agenesis of the Wolffian ducts: zinc-binding properties and effects on sperm chromatin stability

Zinc-binding properties were studied in 'prostatic fluid', i.e. in seminal plasma from patients with agenesis of the Wolffian ducts, and in split-ejaculate fractions dominated by seminal vesicular fluid. The effect of seminal fluid, with different zinc-binding properties, on the stability of zinc-dependent sperm chromatin was assessed by exposing sperm to 1% sodium dodecyl sulphate (SDS) for 60 min. Citrate was the only zinc ligand in 'prostatic fluid', as revealed by gel chromatography. Zinc in this fluid enhanced the stability of sperm chromatin. In contrast, the stability of sperm chromatin was decreased in seminal plasma dominated by vesicular fluid. These results are in accordance with the concept that prostatic fluid ensures the appropriate zinc content and stability of sperm chromatin, whereas abundance of vesicular fluid may jeopardize chromatin stability by reducing chromatin zinc content.     

Aminopeptidase A in reproductive organs of the male rat: evidence for high activity in the posterior lobe of the prostate.

Of the reproductive organs of the male rat a high level of hydrolysis of α-L-glutamyl-β-napthylamide (GluNA) and α-L-aspartyl-β-naphthylamide (AspNA) in the presence of Ca²⁺ (5mM) (aminopeptidase A) was found in the posterior lobe of the prostate. Histochemically, this enzyme was localized in the epithelial cells of acini, which were grouped in the dorsal part and sharply separated from non-active acini in the anterior part of the lobe. A single peak of Ca²⁺-activated GluNA and AspNA hydrolysis was obtained after chromatofocusing at pI 4.9 and on anion exchange chromatography this activity eluted at 0.09 M NaCl. After gel filtration on Sepharose 6B a major peak of activity was found at the elution volume (V_e/V_o= 2.28). In all of these fractionation procedures aminopeptidase A was partially or totally overlapped by other aminopeptidases hydrolysing various amino acid-β-naphthylamides. A pooled enzyme preparation gave an optimum at pH 7.3. The hydrolysis of GluNA was markedly enhanced in the presence of Ba²⁺, Ca²⁺ and Sr²⁺, but the hydrolysis of AspNA was activated only by Ca²⁺ and Sr²⁺. Castration caused a significant decrease in the hydrolysis of GluNA by the posterior lobe, but did not influence the low levels of activity in other parts of the prostate or in the seminal vesicles.     

Seminal vesicle amyloidosis does not provide any protection from invasion by prostate cancer

OBJECTIVE

To determine whether seminal vesicle amyloidosis (SVA, an unusual finding in prostatectomy specimens, with deposits usually localized and asymptomatic) affects the extension of prostate cancer into the SVs.

PATIENTS AND METHODS

We identified 73 cases of localized SVA from 6575 prostatectomy specimens, that were removed because of clinically localized prostate cancer. All cases were confirmed by Congo red staining and polarization microscopy. The mean thickness of the amyloid band was measured in each case and correlated with clinicopathological characteristics. The frequency of SV involvement by prostate cancer in the presence of amyloid was compared with the percentage of pT3b classifications in the absence of amyloid.

RESULTS

The mean (range) age of the patients with localized SVAs was 64.4 (52–73) years. The mean thickness of the amyloid band did not correlate with patient age, preoperative prostate‐specific antigen levels, the weight of the prostates, or the Gleason score and T category of the prostate cancers. In the SVA group, seven cancers invaded the SVs (9.6%), which was not significantly different from the percentage of SV involvement by cancer in total sample (9.2%, P = 0.932).

CONCLUSIONS

The pathogenesis of localized SVA remains poorly understood, but SVA does not seem to provide an absolute or relative protection from SV involvement by prostate cancer.     

Implications of amyloidosis on prostatic biopsy

Transrectal ultrasound-guided biopsy of the prostate is an integral step in the investigation of patients at risk of prostate adenocarcinoma. With an increasing number of biopsies being performed, uncommon forms of prostatic pathology will be identified more frequently. Amyloidosis of the prostate and/or the seminal vesicles may be noted on transrectal ultrasound-guided biopsy of the prostate and the implications of this histological diagnosis must be understood. We present our experience of two such cases of amyloidosis and review the literature regarding their management.     

Effects of Prostaglandins and Indomethacin on the Response of Rat Testis to LH in vivo

In adult male rats, bilateral intratesticular administration of 20 μg PGA₁ or 20 μg indomethacin significantly reduced the acute stimulation of plasma testosterone levels by concomitantly injected LH, while treatment with the same dose of PGF_2α was without effect. After six days of treatment with indomethacin, plasma testosterone levels were reduced to approximately 1/3 of the control levels.
Intratesticular administration of 10 μg LH per testis per day produced, after six days, a precipitous decline in plasma testosterone levels and a decrease in the weight of the testes. This was probably due to desensitization of Leydig cells by these high doses of gonadotropin. Administration of PGF_2α together with LH caused a further decrease in testicular weight and a significant reduction in the weights of the prostate and the seminal vesicles.     

The role of the seminal vesicles and coagulating glands in fertilization in the rat

To investigate the role of the seminal vesicles (SV) and coagulating glands (CG) in fertilization in the rat, partial resections of the SV (25%--group B), 50%--group C, and 75%--group D) or bilateral resection of the SV alone (100%--group E), or together with the CG (group F) were undertaken. In other groups, bilateral resection of the CG only (group G), or bilateral resection of the CG with ipsilateral SV resection (group H) were performed. A group of sham-operated rats served as controls (group A). There were no significant differences among groups A, B, C and D in the number of fertile rats post-operatively but significant differences were evident in groups E, F, G, H when compared with the control group (P less than 0.01 for all groups). Only the fertile rats were able to form copulatory plugs (CP) post-operatively. Bilateral ligation of the SV ducts was performed in ten fertile rats. Post-operatively, the proportion of fertile rats was decreased significantly (P less than 0.01). Removal of the ligatures resulted in a significant increase (P less than 0.01) in fertility. It was also demonstrated that the addition of rat seminal vesicular secretions (SVS) to epididymal sperm suspensions resulted in a significant decrease (P less than 0.001) in sperm motility. These results suggest that the SV and CG are necessary for fertility in rats, and that one role of SVS is the formation of a CP and not the maintenance of sperm motility.