Biological significance of measurable androgen levels in the rat ventral prostate following castration

Within 12 hr after castration, there is a dramatic drop in the serum testosterone (T) levels to approximately 1.3% of the intact value (2.5 +/- 0.8 ng/ml). By 1 day following castration, the serum T levels are approximately 3.3% of the intact control level. In contrast, serum 5 alpha-dihydrotestosterone (DHT) levels decrease to only 50% of the intact value within 12 hr postcastration and remain at a value greater than 50% of the intact control level even following long-term castration for up to 20 weeks. Following castration, tissue T and DHT concentrations in rat ventral prostate (RVP) exhibited a similar sequence of changes. Within 12 hr after castration, there is a substantial decrease in T to 27% and DHT to 20% of their intact values; after a further transient decrease during the subsequent 7 days, these levels remain constant with RVP at approximately 40% for T and 20% for DHT of the intact control levels even following long-term castration. Thus castration induces only a partial withdrawal of the tissue androgens. The low but measurable androgen levels in RVP of castrated host are of adrenal origin, since following surgical adrenalectomy these remaining androgen levels become undetectable. Thus castration plus adrenalectomy produces a complete androgen withdrawal within the RVP. To determine the biological significance of the measurable androgen levels remaining following castration, the RVP cell number and the rate of prostatic DNA synthesis were compared in RVP following castration alone (ie, partial androgen withdrawal) or castration combined with surgical adrenalectomy (ie, complete androgen withdrawal). These results demonstrated that complete elimination of the remaining androgens in the RVP of long-term castrates, by means of surgical adrenalectomy, did not induce any further reduction in either of these prostatic growth parameters. Therefore, in the rat, DHT must be decreased to a critical threshold but does not have to be completely eliminated to decrease maximally androgen effect on the prostate.     

Relationship of thyroid to estramustine binding protein (EMBP) concentration in rat prostate

Alternations of estramustine binding protein (EMBP) concentration in rat prostate in relation to androgen status under hypo- and hyperthyroid conditions was estimated by means of radioimmunoassay (RIA). In hyperthyroid rats, EMBP concentration in dorsal as well as in lateral prostate was not significantly changed, but significantly reduced in ventral prostate (P less than 0.01). Ventral tissue concentration of testosterone(T) + dihydrotestosterone (DHT), DHT and T, and the ventral tissue ratio of DHT to T + DHT were not significantly changed in hypo- and hyper-thyroid conditions compared with that of the control. In hyperthyroid rats, serum T level and EMBP concentration in ventral prostate were significantly reduced in comparison to ones of the control (P less than 0.05 and P less than 0.01, respectively), however, the ratio of ventral tissue (T + DHT) to serum T was significantly increased (P less than 0.05). Moreover, in contrast to the control, EMBP concentration expressed as microgram/microgram ventral DNA was significantly reduced in hyperthyroid rats (P less than 0.05). On the other hand, in hypothyroid rats, change of EMBP concentration in ventral prostate in relation to androgen status was not significant in comparison to the control. The results here obtained revealed that EMBP concentration in ventral prostate under hyperthyroid condition would be affected by (a) a modulation of endogenous androgen-dependency in EMBP synthesis or by (b) a reduction of cell numbers responsible for EMBP synthesis.     

Effect of 5alpha-dihydrotestosterone implants on the fertility of male rats treated with tamoxifen

In adult male rats, tamoxifen (TAM) reduces circulating levels of luteinizing hormone (LH) and testosterone (T) with no effect on follicle-stimulating hormone (FSH) and prolactin (PRL). It reduces the male rat's ability to inseminate the female (potency), as well as its siring ability (fecundity). The objective of the present study was to test whether androgen supplementation could reverse all or some of the observed effects of TAM. To obviate the effects of estrogen, the study was designed to evaluate the beneficial or deleterious effect of 5alpha-dihydrotestosterone (DHT), a 5alpha-reduced, nonaromatizable metabolite of T, on the reproductive functions of TAM-treated adult male rats. Adult male rats received either saline or TAM (0.2 or 0.4 mg per day p.o.) for 90 days. A group of TAM-treated rats was implanted with 6 mg DHT from day 50 to day 90. A third group of untreated animals was implanted with 0-, 1-, 3-, or 6-mg DHT implants for 90 days. Mating studies were done to assess the fecundity, potency, and fertility index at the end of the treatment. Weights of testes, pituitary, and accessory sex organs were recorded, and circulating levels of LH, FSH, PRL, T, and 17-beta-estradiol were estimated. DHT did not affect the fecundity or fertility index. TAM reduced fecundity, potency, and the fertility index. DHT implants improved the fertilizing ability of the TAM-treated male rat. This study discusses and reviews the role of T and 17-beta-estradiol in sperm-fertilizing potential in light of these observations.     

Impact of foetal-onset hypothyroidism on the epididymis of mature rats

It is well established that congenital hypothyroidism leads to male infertility. However, there is a dearth of information on foetal-onset hypothyroidism-induced changes in the epididymis. With regard to transient hypothyroidism, the existing literature deals mainly with the testis. However, it is not known whether there is any corresponding alteration in epididymal morphology and physiology under such a condition. The present study is therefore aimed at understanding the impact of persistent and transient hypothyroidism on the concentration of epididymal sex steroids, as they play a vital role in maintaining the normal structure and function of the epididymis. Normal rats of 90 days of age served as controls (Group I). Hypothyroidism was induced by using pregnant/lactating mothers and post-weaning rats to 0.05% (w/v) methimazole (MMI) in the drinking water. Group II were subjected to persistent hypothyroidism from day 9 of post-coitum (pc) to 90 days. Group III rats were subjected to transient hypothyroidism from day 9 day pc to day 1 post-partum (pp), 21 pp or 35 pp (IIIa, b and c, respectively) and group IV rats were given simultaneous T3 supplementation (3 microg/100 g body wt./day i.m.) with MMI from day 9 pc to day 1 pp; 21 pp and 35 pp (Group IVa, b and c). Animals from all groups were killed on day 90 pp. Serum thyroid stimulating hormone (TSH) and thyroid hormones confirmed euthyroidism in group I, IIIa, b and c and IVa, b and c rats and hypothyroidism in group II rats. Caput and cauda epididymal concentration of testosterone, dihydrotestosterone (DHT), estradiol (E2) and androgen binding protein (ABP) markedly decreased in group II rats. While the concentration of testosterone, E2 and ABP increased in group III rats, that of DHT remained unaltered. However, group IV rats maintained normal concentration of the sex steroid and ABP. The activity of 5-alpha-reductase in the epididymis of all the groups followed the same trend as that of the concentration of epididymal DHT. From the present data it is evident that persistent hypothyroidism diminishes the bioavailability of androgens and oestrogens, while transient hypothyroidism enhances the same, indicating the importance of euthyroidism during foetal and neonatal period towards the maintenance of optimal hormonal status in the epididymis required for its maturation.     

Testosterone and dihydrotestosterone levels in the epididymis, vas deferens and preputial gland of mice during sexual maturation

The levels of testosterone (T) and dihydrotestosterone (DHT) in the epididymis, vas deferens and preputial gland were assessed in mice from 1 to 90 days. The weight increase of these 3 organs was proportionately greater than that of the whole body until 50 or 60 days, and they attained their adult histological appearance approximately 20 days prior to puberty. Expressed in ng/g, the concentration of androgens (T+DHT) in the epididymis (14.3 to 36.5), vas deferens (6.6 to 24.0) and preputial gland (1.5 to 4.7) were higher than in plasma (0.2 to 3.6 ng/ml). The concentration of either androgen varied little during sexual maturation and was not correlated with circulating levels. The highest concentration of androgen (T+DHT) was observed at birth suggesting that the neonatal period is crucial for development of the accessory sexual organs. In the epididymis and preputial gland T was the predominant androgen during the infantile phase of development, whilst DHT predominated thereafter. In the vas deferens concentrations of T were always equal to or higher than those of DHT. These results suggest that the ability of the accessory sexual organs to accumulate androgens appears to be more important than the circulating concentration of androgens in determining their growth and differentiation.     

Spermatogenesis of Rat: Effect of Central Norepinephrine Synthesis Inhibition by Diethyldithiocarbamate

Spermatogenesis and steroidogenesis of male Wistar rats under the influence of a decreased central NE level was studied. Inhibition of NE synthesis was produced by chronic injection (7 days) of DDC, a Dopamine hydroxylase blocker, which decreased brain NE, increased brain DA without significantly affecting brain 5-HT. Rats were sacrificed on the day after cessation of treatment (8th day) and after an interval of 13 days following the cessation of treatment (21st day). The time interval of 13 days is equivalent to one cycle of the seminiferous epithelium in Wistar strain rats. A degenerative change (reduced spermatid count) in the spermatogenic pattern at stage-VII of the cycle of the seminiferous epithelium was observed in the rats sacrificed on the 8th day, the degeneration being much greater in the rats sacrificed on the 21st day. Rats sacrificed on the day after cessation of DDC treatment revealed an inhibition of plasma testosterone level. Such change was not observed in the rats sacrificed after the interval of 13 days following DDC treatment. Human chorionic gonadotropin supplementation in the rats sacrificed on the 21st day partially restored the spermatogenesis towards the vehicle treated control. The inhibition of spermatogenesis and steroidogenesis reflects a decrease in the pituitary gonadotropin secretion under the influence of a decreased NE synthesis in brain, following chronic treatment of DDC.     

Influence of testosterone and dihydrotestosterone on bone-matrix induced endochondral bone formation

Summary A bone matrix-induced endochondral bone development model has been used to study the effects of androgens on different stages of bone development in castrated young adult rats. Androgen treatment, especially with dihydrotestosterone (DHT) for 7 days, inhibited³⁵SO₄ incorporation by the developing cartilage in the induced plaques. Castrated control animals maintained for 11 days after implantation of bone matrix showed significantly lower calcium levels in the induced implant than was observed earlier in the unoperated controls. DHT treatment for 11 days caused dramatic increases in levels of calcium in the implants. Testosterone had little effect. When androgen treatment was continued for 21 days, while levels of alkaline phosphatase in the implants were unaffected, levels of calcium in the implants were significantly higher than on day 11 for both castrated control and androgen-treated animals. Peak alkaline phosphatase activity (day 10) is known to precede peak calcium mineralizing activity (day 12) in this model and it is also known that calcium levels remain high thereafter. Evaluation of calcium and alkaline phosphatase levels in the proximal tibial metaphyses of castrated control and androgen-treated groups of animals showed no changes after 11 days treatment. Prolonged treatment (21 days) elevated the levels of alkaline phosphatase whereas no change was observed in calcium levels in the tibial metaphyses. These findings demonstate that androgens stimulate mineralization and that DHT is more active when used for short periods of time and in early stages of bone development in matrix-induced implants.     

Protein C inhibitor expression by adult rat Sertoli cells: effects of testosterone withdrawal and replacement

Protein C inhibitor (PCI), a member of the plasma serine protease inhibitor family, has been reported to be abundantly expressed in the seminal vesicles and testes. In this study, we examine the localization and regulation of the PCI gene and protein expression in testes and freshly isolated Sertoli cells from control rats, rats treated with luteinizing hormone-suppressive testosterone/estradiol (TE)-containing Silastic capsules for 7, 14, 28, and 56 days, and rats treated with TE for 56 days, followed by high levels of testosterone for 7 or 14 days. The administration of the TE capsules for 56 days resulted in reduced testicular testosterone, from approximately 100 ng/mL in the controls to approximately 10 ng/mL, accompanied by a 73% reduction in testicular weight. PCI mRNA levels in freshly isolated Sertoli cells were reduced by 30% and 54% following TE treatment for 28 and 56 days, respectively. When rats that had received TE capsules for 56 days were provided replacement testosterone, there was a 40% increase in PCI mRNA levels within 7 days in the absence of any change in testicular weight, and PCI mRNA levels returned to control values by 14 days. The decrease in PCI mRNA levels in TE-treated rats was paralleled by a decrease in PCI protein levels in whole testis lysates and in seminiferous tubule fluid (STF). Protease activity was significantly increased in STF following 56 days of TE treatment. Taken together, these results indicate that 1) PCI in the testis is expressed by Sertoli cells; 2) the testicular expression of PCI is responsive to intratesticular testosterone levels; and 3) protease activity within the seminiferous epithelium is elevated when intratesticular concentration is decreased, perhaps as a consequence of decreased PCI.     

Influence of hormone treatment on prostate growth and micturition characteristics of the rat

The influence of dihydrotestosterone propionate (DHT) and estradiol (E) on prostate growth and micturition was evaluated. Complete studies were carried out on 49 Sprague-Dawley rats over a 14-day period. Rats were divided into three groups: (1) controls, (2) DHT, and (3) DHT + E. All groups were injected daily with 0.1 ml of sesame oil, together with 1.25 mg/kg of DHT for group 2 and 1.25 DHT + 0.125 mg/kg E for group 3. Physiological measurements of micturition were done weekly by subcutaneously administering a fluid loading dose consisting of 10 mg/kg furosemide + 5 ml saline. Parameters of micturition frequency, volume, and prostate weight were calculated. Prostate weight values for controls were 0.89 ± 0.06 g while those treated with DHT increased significantly to 1.26 ± 0.10 g (P < 0.05) and those treated with DHT + E also increased significantly to 1.24 ± 0.09 g (P < 0.05). There was no significant difference in prostate weight between the DHT and DHT + E groups. Analysis of micturition data shows that the mean volume voided per micturition decreases in both the DHT and DHT + E treated rats. At between 7 and 14 days of DHT and DHT + E treatment, rats micturated at significantly reduced mean volumes. The lowest mean volume per micturition was detected on the 14th day of DHT treatment, showing a significant reduction from control values of 3.05 ± 0.27 to 1.68 ± 0.05 ml. The corresponding value of the mean micturated volume in the DHT + E groups was 1.86 ± 0.31 ml. Control values for frequency of micturition was 3.25 ± 0.52/hr, while for rats treated with DHT it was 3.62 ± 0.38/hr and for DHT + E it was 4.0 ± 0.54/hr. Evidence is provided to demonstrate that 14 day DHT, and particularly DHT + E, stimulation produces significant alterations in prostate weight and micturition characteristics of unanesthetized rats. On the basis of these observations it is proposed that the hormonally enlarged prostate promotes stimuli to trigger the spinal micturition reflex, thereby producing increased frequency of micturition. © 1996 Wiley-Liss, Inc.     

In vitro and in vivo effects of vitamin D (calcitriol) administration on the normal neonatal and prepubertal prostate

PURPOSE: Although many studies have investigated the role of calcitriol in the growth regulation of normal and cancerous prostates, little is known about its role in early prostatic development. The interactions between calcitriol and androgens, and their actions on the normal prostate have similarly been proposed but not evaluated. Previous studies in our laboratory have revealed that in utero administration of 1,25-dihydroxycholecalciferol or calcitriol can influence prostate growth and differentiation throughout the life of the animal. We further examined the influence of calcitriol on the normal prostate in vitro and in vivo by focusing on early stages of prostatic development. MATERIALS AND METHODS: The effects of calcitriol on the growth of the normal human neonatal prostatic epithelial cell line 267B-1 was determined in the presence and absence of dihydrotestosterone (DHT). We also examined the effect of calcitriol on the growth of maturing rat prostates in vivo. Before puberty 4 groups of rats 27 to 38 days old were treated with vehicle (controls) or calcitriol. When the rats reached adulthood at age 100 to 110 days a control group and a calcitriol group were sacrificed. The other 2 groups were given exogenous DHT for 5 days. For the animals to become adapted to DHT they were kept alive for 1 additional week and sacrificed at about age 120 days. RESULTS: In vitro studies demonstrated that 267B-1 cells possess vitamin D receptors and their growth was inhibited by calcitriol with an IC50 (concentration resulting in 50% cytotoxicity) of 30 microM. Proliferation of these neonatal prostate cells was also inhibited by calcitriol in the presence of DHT in vitro. Our studies indicate that, although calcitriol was administered at the apparently important prepubertal period, there was no difference in prostatic weights between the control and calcitriol treated rats. Exogenous administration of DHT decreased prostatic weight of control rats but in rats treated with 1,25-dihydroxycholecalciferol DHT did not have any significant effect on prostatic weight. No statistically significant differences were observed in seminal vesicle weights among the different groups of animals. Analysis of the nuclear matrix protein composition of the prostatic tissue showed differences in composition between the DHT, and calcitriol and DHT treated rat prostates. CONCLUSIONS: These studies indicate that calcitriol administered just before puberty does not significantly influence prostatic growth in the presence of endogenous or exogenous administered DHT, and has an inhibitory effect on neonatal prostate epithelial cell growth in vitro in the presence and absence of DHT. Treatment with calcitriol and DHT also results in differences in nuclear matrix protein composition. Prepubertal administration of calcitriol may inhibit the exogenous DHT action in decreasing epithelial growth and stimulating stromal proliferation in the rat prostate.     

DHEA Administration Activates Local Bioactive Androgen Metabolism in Cancellous Site of Tibia of Ovariectomized Rats

It is not known whether local androgen metabolism is involved in the mechanisms underlying the dehydroepiandrosterone (DHEA) administration-induced improvement of bone mineral density (BMD) in an estrogen-deficiency state. The aim of the present study was to clarify whether DHEA administration would improve local androgen metabolism and BMD in cancellous site of tibia of ovariectomized (OVX) rats. Twenty-two female rats, 6 weeks old, were randomized into three groups: sham-operated rats, OVX control rats, and OVX rats that received DHEA treatment. DHEA was administered intraperitoneally at 20 mg/kg body weight for 8 weeks. The concentrations of free testosterone and dihydrotestosterone (DHT) in cancellous site of tibia did not change as a result of ovariectomy, while the DHT concentration increased following DHEA administration. We revealed that DHEA administration improved the reduction of 17β- and 3β-hydroxysteroid dehydrogenases and clearly reversed the reduction of 5α-reductase types 1 and 2 and androgen receptor in the cancellous site of tibia of OVX rats. DHEA administration suppressed estrogen deficiency relative to the decrease in the cancellous BMD, which was positively associated with local DHT concentration. These findings indicate that DHEA administration enhances local bioactive androgen metabolism in the cancellous tibia of young OVX rats, suggesting that local DHT may play a part in the DHEA administration-induced improvement of cancellous BMD.     

Differential effect of hyperthyroidism on rat epididymal glycosidases

The impact of hyperthyroidism on epididymal glycosidases was studied in albino rats. Hyperthyroidism was induced in Wistar rats aged 30 days by daily injection of T4 (25 microg/100 g body weight/day intramuscularly) for 30 or 60 days; control rats were injected with vehicle (alkaline saline, pH 7.8). One set of hyperthyroid rats was reverted to euthyroid status by withdrawing T4 treatment after 30 days of hyperthyroidism. To asses the direct effect of thyroid hormone on epididymal hexosaminidases, caput, corpus and cauda tissues were stimulated with 25, 50 or 100 ng/mL T3 for 24 h, after an initial culture of 24 h. The activity of beta-glucosidase decreased in caput, corpus and cauda epididymis of hyperthyroid rats. beta-Galactosidase activity increased in the caput epididymis irrespective of the duration of hyperthyroidism. While a similar decrease occurred in the corpus and cauda epididymis in the 30 day hyperthyroid group, an opposite trend was observed in 60 day hyperthyroid rats. Caput beta-N-acetylglucosaminidase activities increased at both time points, whereas activity decreased in the corpus and cauda in 30 day, but increased in 60 day hyperthyroid rats. Hyperthyroidism consistently increased caput and corpus beta-N-acetylgalactosaminidase activity irrespective of the duration. Cauda epididymal beta-N-acetylgalactosaminidase activity was decreased in 30 day and increased in 60 day hyperthyroid rats. Hyperthyroidism induced changes in caput beta-galactosidase, beta-N-acetylgalactosaminidases, corpus beta-N-acetylglucosaminidase and cauda beta-N-acetylgalactosaminidase which were irreversible while the remaining actvities were brought back to normal when T4 treatment was withdrawn. In vitro studies showed that T3 stimulates epididymal hexosaminidases (beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase) irrespective of the dose. These data suggest that thyroid hormones have a specific and direct influence on glycosidases in specific regions of the epididymis.     

Effect of 5-α-reductase inhibition and dexamethasone administration on the growth characteristics and intratumor androgen levels of the human prostate cancer cell line PC-3

The endocrine treatment of metastatic prostate cancer includes castration which reliably lowers the serum testosterone (T); however, the effect on intratumor levels of T and dihydrotestosterone (DHT) is less predictable. In vitro work demonstrated that the human prostate cancer cell line PC-3 had significant 5-a-reductase activity that could be inhibited with 17b-N, N-diethylcarbamoyl-4-aza-5a-androstan-3-one (4MA). In this study, we examined the effect of 5-a-reductase inhibition with 4MA and androgen suppression with dexamethasone on the growth characteristics and intratumor androgen levels in the PC-3 cell line in male athymic nude mice (Balb/c). The mice were randomized into six treatment groups: 1) noncastrate vehicle control, 2) 4MA, 0.25 mg/day, 3) 4MA, 1 mg/day, 4) dexamethasone, 25 μg/day, 5) 4MA, 1 mg/day, and dexamethasone, 25 μg/day, and 6) castrate control group. After 21 days of treatment the animals were sacrificed, serum collected, and tumors harvested. Each treatment produced intratumor DHT levels equivalent to the castrate group. Only the low dose 4MA caused a reduction in intratumor DHT without producing castrate levels of circulating T. The combination of dexamethasone and 4MA was less effective in lowering the intratumor DHT/T ratio than 4MA alone. No significant differences in tumor growth parameters were noted between intact control animals and any of the treatment arms. Serum T levels correlated poorly with intratumor androgen levels. Five-a-reductase inhibition produced castrate levels of intratumor DHT in the nonandrogen-dependent prostate cancer cell line PC-3. The combination of dexamethasone and 5-a-reductase inhibition with 4MA appears to be less effective in lowering intratumor androgen levels than either therapy alone. © 1994 Wiley-Liss, Inc.     

The effects of flutamide on total DHT and nuclear DHT levels in the human prostate

The effects of flutamide, an antiandrogen, on prostate tissue concentrations of total DHT, DHT present in both crude and purified nuclear fractions, prostatic acid phosphatase (PAP) and plasma testosterone were studied and compared to similar parameters in untreated benign prostatic hypertrophy (BPH). Flutamide was given to patients with BPH in a dosage of 750 mg per day by mouth for 10–14 days prior to transurethral resection of the prostate. Total prostate DHT was significantly decreased to 3.95 ng/g in 12 flutamide-treated patients compared to values of 6.61 ng/g in 12 patients with untreated BPH. However, no significant difference was noted in the concentration of DHT present in the crude nuclear fraction of flutamide-treated patients (646 pg/mg DNA, N = 5) and untreated BPH (882 pg/mg DNA, N = 10); nor was DHT in the purified nuclear fraction significantly different in drug versus untreated patients (251 pg/mg DNA for flutamide versus 353 pg/mg DNA for untreated controls). PAP concentration in BPH prostates was 7.11 S.U./mg wet weight and was significantly higher than 2.98 S.U. per mg wet weight noted in flutamide-treated patients. Plasma testosterone tended to rise in the flutamide-treated patients compared to the untreated BPH but this was not statistically significant. The decrease in total prostate DHT without changes in nuclear DHT was unexpected and difficult to explain in terms of current tenets regarding the mechanism of androgen action. The following hypotheses are offered: (a) Flutamide may decrease transport of testosterone into cells, thereby decreasing total prostate DHT. (b) Inhibitory effects of flutamide on receptor-bound DHT translocation to nuclei may be difficult to detect since 95% or more of nuclear DHT may not be bound to a salt extractable receptor. (c) The binding of DHT directly to putative nuclear matrix receptor sites may dilute the effects of flutamide on blocking translocation of receptor bound DHT, resulting in very small differences in DHT present in purified nuclei difficult to detect with current methodology.     

Effects of steroids on oxytocin secretion by the human prostate in vitro

Oxytocin (OT) concentrations are elevated in prostate tissue of patients with benign prostatic hyperplasia (BPH). Oxytocin specifically increases growth, 5 alpha-reductase activity and contractility in the prostate. In the rat prostatic OT concentrations are regulated by gonadal steroids, with androgens reducing but oestrogens increasing OT concentrations. The regulation of prostatic oxytocin in man is not understood. This study investigates the effects of gonadal steroids on oxytocin production by the human prostate. Primary explants (approx. 1 mm3) of prostate tissue from patients with BPH were incubated in Dulbecco's modified Eagle's media in the absence or presence of 10 nmol/L testosterone (T), 10 nmol/L dihydrotestosterone (DHT), T or DHT plus 100 nmol/L of the anti-androgen cyproterone acetate (CPA), 55 pmol/L diethylstilbestrol (DES), or DES plus DHT. The amount of oxytocin secreted into the media after 3 days was measured by radioimmunoassay. Testosterone and DHT significantly increased oxytocin concentrations secreted into the media from 0.86 +/- 0.11 ng/g of tissue (control) to 1.51 +/- 0.14 ng/g (p < 0.01) and 1.54 +/- 0.13 ng/g (p < 0.05), respectively. Incubation of tissue samples with CPA resulted in oxytocin concentrations similar to control levels. Treatment with DES caused a significant increase from 1.99 +/- 0.71 to 3.98 +/- 1.36 ng/g (p < 0.05). A similar increase was measured in media of tissue incubated in DES plus DHT (p < 0.001). The results demonstrate that, unlike the rat where androgens decrease oxytocin, in hyperplastic human prostate tissue both androgens and oestrogens increase oxytocin. This imbalance in the regulation of oxytocin may result in promoting prostatic overgrowth in the pathogenesis of BPH.     

万古霉素对细菌性前列腺炎及良性前列腺增生合并细菌性前列腺炎大鼠的前列腺透过性及其治疗效果研究

目的:了解万古霉素对大鼠急性细菌性前列腺炎(BP)以及良性前列腺增生(BPH)合并BP的前列腺透过性与治疗效果。方法:采用每天由尾静脉注射1次万古霉素(100 mg/kg体重)共5 d的方法,分别对正常前列腺(NP,n=42)、BP(n=73)以及BPH合并BP(n=43)的SD雄性大鼠给药。注射后10 m in~24 h分离动物血清和前列腺,分别以琼脂扩散法及最低抑菌浓度(M IC)法检测血清抗生素活性,同时对前列腺进行病原菌的分离培养与计数;治疗结束后1~5周,分离BP治疗组动物的前列腺,进行病理学检查。结果:正常大鼠的前列腺组织内始终不能检出任何病原菌,未注射万古霉素的BP组大鼠前列腺组织至感染后的28 d仍可检出不同数量的病原菌。各BP治疗组动物的前列腺组织内病原菌的数量随给药时间延长而逐渐明显减少,在给药第5 d后91.7%的动物的前列腺组织已不能检出病原菌。各组大鼠给药后10~150 m in期间,其血清及前列腺组织内均可检出明显的抗生素活性,前列腺组织的M IC为0.05~0.005 g/m l,分别低于、等于或高于同期的血清抗生素活性。在给药6 h和24 h后,各组大鼠的血清与前列腺组织内已不能检出抗生素活性。组织病理学检查可见BP组大鼠的前列腺组织表现出明显的渗出、白细胞浸润,BPH组大鼠的前列腺具有明显的腺组织增生。随给药时间延长以及前列腺病原菌数量的减少或消失,BP组大鼠前列腺的组织炎性病理学改变可明显缓解。结论:静脉注射的万古霉素能够进入大鼠急性细菌性炎症前列腺以及BPH合并细菌性炎症前列腺的组织内,并且达到等于或高于血清抗生素浓度的水平,从而能够有效地杀灭前列腺组织内的敏感细菌,以促进前列腺组织的炎症反应缓解及其损伤组织的修复。     

肝部分切除术后大鼠认知功能及β淀粉样蛋白的变化

目的 评价大鼠肝部分切除术后认知功能及β淀粉样蛋白(Ap)的变化.方法 健康雄性sD大鼠70只,体重200～250 g,随机分为3组:对照组(C组,n=12)、麻醉组(A组,n=29)和肝部分切除术组(PH组,n=29).A组和PH组于术后1 d(T1)和7 d(T3)时各取7只大鼠,采用Y型迷宫检测术后第1、2、3、7、8、9天时学习记忆能力;于术后1 d(T1)、3 d(T2)和7 d(T3)时取5只大鼠,取左侧海马,并断尾取血,测定Aβ表达;取右侧海马采用荧光定量PCR测定App mRNA表达.结果 与C组相比,PH组术后学习记忆能力下降,T1,3时血清Aβ浓度降低,T1-3,时海马Aβ含量升高,TI时App770mRNA含量升高(P＜0.05);与A组相比,PH组术后学习记忆能力下降,T1,3时血清Aβ浓度降低,T1-3时海马Aβ含量升高,T1时App770 mRNA含量升高(P＜0.05).结论 肝部分切除术后大鼠发生短期认知功能减退,可能与海马Aβ含量升高有关.     

重组人生长激素对大鼠肠缺血再灌注后肠壁组织T淋巴细胞亚群和浆细胞的影响

目的　探讨肠道屏障功能损害时应用重组人生长激素(rhGH )对肠道免疫屏障中肠黏膜及固有层内T淋巴细胞亚群和浆细胞的影响。方法　将60只Wistar大鼠雌雄各半随机分为实验组和对照组,按实验天数(2、4、6d)又各分为3组,每组10只,以肠缺血再灌注模型造成肠道屏障功能损害的病理现象,实验组给与rhGH (每日1.3 3U/kg体重) ,观察回肠末端黏膜固有层内CD8+、CD4+、CD3 +T淋巴细胞数及IgA浆细胞的数量变化。结果　(1)实验组CD8+、CD4+、CD3 +T及IgA浆细胞第6天与第2、4天比较数量显著增多,差异有统计学意义(P <0 .0 5 )。(2 )实验组与对照组第6天,CD8+、CD4+T及IgA浆细胞的数量实验组均高于对照组,差异有统计学意义(P <0 .0 5 )。(3 )CD4+/CD8+比值第2天两组差异有统计学意义(P <0 .0 5 )。结论　肠道屏障功能损害时应用重组人生长激素能够调节肠黏膜的免疫屏障,其作用时间在第6天可能最明显     

Effect of testosterone, estradiol-17 beta, and 5 alpha-dihydrotestosterone on inhibin production by sertoli cells in culture

Inhibin activity in charcoal-extracted spent culture medium of Sertoli cells in Primary culture (CSCCM) was monitored by following the temporal inhibition of serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in normal adult male rats. Subcutaneous injection of CSCCM reduced LH and FSH levels within 15 min and maintained the inhibition up to 10 hr. No selective suppression of FSH was observed. The model was used to assess inhibin activity in CSCCM from Sertoli cell cultures incubated with 5 alpha-dihydrotestosterone (DHT), testosterone (T), and estradiol -17 beta (E2) (5 micrograms/ml) for 24 hr. CSCCM from T and E2 treated groups suppressed gonadotropins while the group exposed to DHT failed to elicit any inhibition. DHT seems to inhibit the release of inhibin by Sertoli Cells.     

Chronology and urodynamic characterization of micturition in neurohormonally induced experimental prostate growth in the rat

The purpose of this study was to evaluate the impact of chronic urinary tract obstruction which was produced in the rat using neurohormonally induced experimental prostate growth. In this model, we considered the chronology of changes in the micturition characteristics of awake rats relative to prostate weight and stiffness. The corresponding urodynamic characteristics of both the upper and lower tracts were evaluated in anesthetized animals relative to the development and extent of the obstruction produced. Prostate growth was produced by capitalizing on the synergistic properties afforded by the combined administration of dihydrotestosterone propionate (DHT) and the α1 adrenoreceptor antagonist prazosin (PRZ). DHT (1.25 mg/kg/day) was dissolved in 0.1 ml sesame oil (SO) and coadministered with PRZ 30 μg/kg/day subcutaneously for 14 days to 12 experimental rats. SO alone was given to 8 control rats. Micturition studies were first performed using all 20 awake rats, which were placed unrestrained in metabolic cages. Urodynamics of the upper and lower urinary tracts were repeated following anesthesia at the 5th, 10th, and 15th weeks after initiation of hormonal or SO treatment. Following the urodynamic studies, the rats were killed and prostates were removed and weighed, and stiffness was measured. Studies with awake rats show that hormonal treatment produces a significant and progressive increase in mean frequency of micturition, ranging from 0.63 ± 0.16 in controls and reaching the maximum of 2.15 ± 0.40/hr by the 10th wk. Results from urodynamic studies with anesthetized rats also show typical and progressive obstructive characteristics: maximum detrusor voiding pressure (P_detmax) increased from 52.7 ± 2.03 in controls to a maximum of 77.5 ± 2.2 cm H₂O by the 10th week; urethral opening pressure P_uo likewise increased from 52.6 ± 2.7 in controls to 73.3 ± 2.1 cm H₂O in experimental rats. The duration of time during which the detrusor sustains contraction during voiding also rose, from 16.8 ± 1.8 sec in controls to 32.0 ± 3.2 sec by the 10th week. There were no significant changes in bladder capacity, baseline filling pressures, or arterial pressures. Prostate weight increased significantly from 0.76 ± 0.05 g in controls to 1.17 ± 0.1 g by the 15th week. Similarly, stiffness increased from control values of 1.33 ± 0.18 g/cm to a maximum of 3.59 ± 0.14 g/cm by the 10th week. It is concluded that neurohormonally stimulated prostate growth in the rat is a suitable animal model for the study of the development of urinary tract obstruction. Obstructive characteristics were validated in both awake rats by the increase in the frequency of micturition and urodynamically under anesthesia in terms of elevations in maximum detrusor pressures, urethral opening pressure, detrusor contraction time, and prostatic stiffness. The effect of obstruction was further shown to be associated with vesicoureteral reflux during micturition and elevated upper tract pressures. Neurourol. Urodyn. 17:55–69, 1998. © 1998 Wiley-Liss, Inc.