Smooth muscle cells (SMC) play roles in prostatic development and function. The cells also respond to tissue injury and hormonal variations, alternating between a fully differentiated and contractile phenotype and a dedifferentiated synthetic or secretory phenotype. However, the phenotypic changes in SMC after androgen deprivation have not yet been described. The ventral prostate of control and castrated rats was processed for routine histology, immunocytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR), and scanning electron microscopy (SEM). The maintenance of SMC phenotype was confirmed by immunocytochemistry and by RT-PCR. Stereological analyses were done to define the relative and absolute volume of the SMC. SMC were elongated and flattened against the epithelium. After castration, the cells shortened concomitantly with pleating of the cell surface, leading to a spinous aspect. SEM showed that the smooth surface of SMC became progressively folded. Immunocytochemistry demonstrated both smooth muscle myosin heavy chain and smooth muscle alpha-actin in the prostatic SMC 21 days after castration, whereas RT-PCR amplified the message for smoothelin. Stereological analysis showed an increase in the relative volume of SMC in relation to the whole gland and the stroma. A decrease in the absolute volume of SMC occurred only within the first 7 days after castration and remained unchanged thereafter. The prostatic SMC are affected by the absence of androgens and there is a critical transition point during the first week in which the total volume occupied by SMC diminished. The remaining SMC showed a marked phenotypical change. These findings indicate that ventral prostate SMC maintain their differentiated phenotype after castration. The alterations in SMC behavior correlate with general stromal modifications taking place after castration.
Hyaluronan (HA) has been implicated in tissue remodeling, healing, and tumor growth. This study investigated the variation in hyaluronan content, distribution, and metabolism in the rat ventral prostate (VP) in response to androgen deprivation after castration. The mRNA abundance of hyaluronan synthases (Has1-3) and hyaluronidases (Hyal 1-3) were assessed by reverse transcription (RT)-PCR and immunohistochemistry, respectively. The results demonstrated an increased concentration, but an overall reduction in HA content. HA was located in both epithelium and stroma of the prostate of both the noncastrated and castrated animals. Quantitative RT-PCR (qRT-PCR) showed that Has1 and Has2 are major synthases, and that Hyal 1 was the predominant hydrolase expressed in the VP. qRT-PCR also showed that Has1 and Has2 mRNA increased transiently after castration, whereas Has3 mRNA declined markedly. While Hyal 1 mRNA increased slowly up to day 21 after castration, Hyal 2 and Hyal 3 mRNA dropped significantly. CD44 was found in the epithelial cells and in some stromal cells in both hormonal conditions. In conclusion, castration results in increased abundance of Has1 and Has2 mRNA, but is associated with a decrease in the total content of HA, with an increased concentration, and a predominance of short-chain HA molecules.
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