Smooth Muscle Cell Behavior in the Ventral Prostate of Castrated Rats

Abstract

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.

Early effects of estrogen on the rat ventral prostate

“…A similar reduction in SMC volume after castration has been reported before (37) and was suggested to be the result of cellular atrophy or cell loss by apoptosis.…”

“…Further weight loss will depend on other alterations of the gland that cannot be anticipated by E2. Most likely, E2 was unable to anticipate later stromal changes seen in castrated animals (37,40), which may be necessary for further prostatic involution.…”

Testosterone and Erectile Function: From Basic Research to a New Clinical Paradigm for Managing Men with Androgen Insufficiency and Erectile Dysfunction

“…Regulation of progenitor cell differentiation is a complex process, dependent on numerous hormones, growth factors, and specific activation of a cascade of gene expression [42,[46][47][48][49][50][51].Critical regulators of adipocyte differentiation include C/EBPα (CCAAT/enhancer binding protein), PPARγ2 (peroxisome proliferator-activated receptor), and LPL (lipoprotein lipase) [47,48,[52][53][54][55][56][57]. Alternatively, transdifferentiation of smooth muscle cells into other phenotypes may occur [58][59][60][61]. Inhibition of 5α-reductase activity induces stromal remodeling and smooth muscle dedifferentiation in the prostate, suggesting that 5α-DHT deficiency promotes smooth muscle dedifferentiation [62].…”

Dynamics of the Epithelium During Canalization of the Rat Ventral Prostate

“…A total of 144 dots/72 grid lanes were analyzed as described previously for the ventral prostate (Huttunen et al, 1981;Antonioli et al, 2004;Garcia-Florez et al, 2005). Four or five microscopic fields taken at random were analyzed per animal (n 5 3), resulting in 13-15 fields per group.…”