Cavett W, Cason Z, Tucci M, Puckett A, Benghuzzi H
University of Mississippi Medical Center, Jackson 39216, USA.
Biomed Sci Instrum. 1997;34:30-5.
Previously, our laboratory has reported that tricalcium phosphate lysine drug delivery system (TCPL) can be used successfully to deliver dihydrotestosterone (DHT) and testosterone (T) at a sustained manner for long duration. The objective of this study was to evaluate the effects of estrogen (E), DHT and dehydroepiandrosterone (DHEA), delivered in a sustained manner, individually or in combination, by means of TCPL delivery system on the morphological changes of ventral prostatic tissue. Adult male rats (BW 300-350 gm) were randomly divided into four equal groups. Animals in Group I served as our intact unimplanted controls. Capsules implanted in Group II rats were loaded with TCPL containing 100 mg of DHEA. Rats in Group III were implanted with TCPL loaded with 100 mg of DHEA and 500 mg of DHT, while rats in Group IV were implanted with TCPL loaded with 100 mg of DHEA, 500 mg of DHT and 200 mg of E. Surgical aseptic techniques were performed according to standard laboratory procedures. The animals were maintained at the University of Mississippi Medical Center Animal Facilities following the rules and regulations established by NIH on the Care and Use of Laboratory Animals. At the end of 8 weeks post implantation, all animals were sacrificed and the prostatic tissues were collected, weighed and embedded for histopathological evaluations. Statistical analysis was conducted by using standard computer programs (STATEVIEW, JANDEL, ANOVA at 95% CI). The data obtained in this investigation demonstrated that exogenous intake of E + DHEA + DHT delivered in a sustained manner for eight weeks induced several pathophysiological conditions in ventral prostatic tissue in comparison to prostatic tissue collected from control animals. Cytopathological evaluations of tissue collected from Group II animals demonstrated the following: (i) atrophic pattern of the epithelium, (ii) small, round glands with low cuboidal epithelium, (iii) hypertrophy alone or in conjunction with occasional hyperplasia of the epithelial cells, and (iv) an increased presence of connective tissue stroma. In contrast, ventral prostate collected from animals in Group IV showed an increase in weights of the net prostatic tissues in comparison to the control group. Histopathological observations such as pleomorphism, low cuboidal to pseudostratified glands, prostatic hyperplasia of the epithelial cells, occasional mitotic activity, and occasional presence of connective tissue stroma were detected. In conclusion, the results of this study suggest that the use of TCPL capsules loaded with steroid hormones, individually or in combination can be used to regulate the growth and functional behavior of prostatic tissue in male rodents.
此前，我们实验室已报道磷酸三钙赖氨酸药物递送系统（TCPL）可成功用于长期持续递送二氢睾酮（DHT）和睾酮（T）。本研究的目的是评估通过TCPL递送系统单独或联合持续递送雌激素（E）、DHT和脱氢表雄酮（DHEA）对前列腺腹侧组织形态变化的影响。成年雄性大鼠（体重300 - 350克）被随机分为四组。第一组动物作为完整未植入的对照。第二组大鼠植入的胶囊装载有含100毫克DHEA的TCPL。第三组大鼠植入装载有100毫克DHEA和500毫克DHT的TCPL，而第四组大鼠植入装载有100毫克DHEA、500毫克DHT和200毫克E的TCPL。按照标准实验室程序进行手术无菌操作。动物饲养于密西西比大学医学中心动物设施，遵循美国国立卫生研究院制定的关于实验动物饲养和使用的规则和条例。植入后8周结束时，处死所有动物，收集前列腺组织，称重并包埋以进行组织病理学评估。使用标准计算机程序（STATEVIEW、JANDEL、95%置信区间的方差分析）进行统计分析。本研究获得的数据表明，与从对照动物收集的前列腺组织相比，持续8周外源性摄入E + DHEA + DHT会在前列腺腹侧组织中诱导多种病理生理状况。对从第二组动物收集的组织进行细胞病理学评估显示如下：（i）上皮萎缩模式，（ii）具有低立方上皮的小圆形腺体，（iii）上皮细胞单独肥大或伴有偶尔增生，以及（iv）结缔组织基质的存在增加。相比之下，与对照组相比，从第四组动物收集的前列腺腹侧显示净前列腺组织重量增加。检测到组织病理学观察结果，如多形性、低立方到假复层腺体、上皮细胞的前列腺增生、偶尔的有丝分裂活动以及偶尔存在的结缔组织基质。总之，本研究结果表明，单独或联合装载类固醇激素的TCPL胶囊可用于调节雄性啮齿动物前列腺组织的生长和功能行为。
