Effect of pubertal development on estrogen receptor levels and stromal morphology in the guinea pig prostate

Abstract

Using an immunocytochemical assay (ERICA) with a monoclonal antibody (H222Sp gamma) to the human estrogen receptor, we have demonstrated a stromal localization of the estrogen receptor in the dorsolateral prostate of the guinea pig. Specific staining of estrogen receptor in the guinea pig prostate was confined to the nuclei of periacinar and interacinar stromal cells. In comparison with prepubertal tissues, estrogen receptor staining intensity was markedly reduced in postpubertal prostatic tissues. No immunoreactive estrogen receptor was detected in the acinar epithelial cells irrespective of the developmental stage of the guinea pig prostate. Electron microscopic examination of the guinea pig prostate showed that the stromal component consists predominantly of smooth muscle cells, which, during pubertal development, undergo marked cytological changes and increase in size. These changes in the prostatic stroma were associated with a greater than fivefold reduction in levels of cytosolic and nuclear estrogen receptor determined by either a radioligand binding assay or an enzyme immunoassay (EREIA) and expressed relative to soluble protein. Morphometric analysis of the prostatic stromal cell density (SCD: nuclei/mm2 interacinar stroma), which is inversely proportional to stromal cell size, indicated that the SCD decreased approximately threefold during pubertal development. Furthermore, cytosolic estrogen receptor levels in mechanically separated prostatic stromal fractions were found to vary concordantly with the SCD during pubertal development. To determine whether estrogen influences normal development of the guinea pig prostate, the effect of various hormonal manipulations on stromal development was examined. Castration of prepubertal animals prevented the threefold decrease in SCD that is characteristic of pubertal development. Treatment of prepubertal castrates with estradiol and 5 alpha-dihydrotestosterone (DHT) in combination over a period equivalent to the transpubertal growth phase resulted in a stromal cell density similar to that seen in prostatic sections from intact postpubertal animals. In contrast, treatment of prepubertal castrates with either estradiol or DHT alone resulted in a prostatic stromal cell density intermediate between that observed in intact prepubertal and postpubertal animals. These findings suggest that both estrogen and androgen are required for the normal development of the guinea pig prostatic stroma.

Genistein reduces the noxious effects of in utero bisphenol A exposure on the rat prostate gland at weaning and in adulthood

“…It clear that the change in the pattern of collagen budding with reduction in relative proportion of stroma compartment caused by gestational BPA exposure resulted in changes in the distribution and aggregation of extracellular matrix elements (Brandt et al, 2014). Previous reports have shown that exposure to estradiol may increase the synthesis of collagen in the stromal cells and make collagen bundles thicker in rodent prostate (Tilley et al, 1989;Prins et al, 2007;Scarano et al, 2005Scarano et al, , 2008. However, serum levels of estradiol on PND21 did not differ among the experimental group but some toxicological studies in which EDs were administered during pregnancy showed that hormone levels tend to normalize after exposure; however, the tissue-specific effects remain (Putz et al, 2001;Scarano et al, 2009).…”

The role of estrogens and estrogen receptors in normal prostate growth and disease

“…only a portion of the cells are ERα positive while many remain ERα negative. Studies in rodent prostate glands have shown a relatively high percentage of stromal cells express ERα mRNA and protein during perinatal morphogenesis and this proportion significantly declines thereafter suggesting a specific role for ERα in prostate development [73,75,76]. A decline in expression with puberty suggests that androgens may normally suppress ERα expression, a finding that has been borne out in direct studies [77,78].…”

Developmental estrogen exposures predispose to prostate carcinogenesis with aging☆

“…Since AR are induced in rat prostate epithelium by postnatal day 1-3, it is possible that androgen-driven epithelial signals also contribute to morphogenesis and differentiation of the prostate (15) The developing prostate gland also expresses other members of the steroid receptor superfamily including estrogen receptors ERα and ERβ and retinoic acid receptors RARα, β and γ which are liganded by all-trans or 9-cis retinoic acid as well as RXR α, β and γ which are activated by 9-cis retinoic acid alone. Studies in rodent prostate glands have shown relatively high stromal cell ERα expression during perinatal morphogenesis of the gland which significantly declines thereafter suggesting a specific role for ERα in prostate development (16,18,19). In the rat and murine prostate, ERβ is primarily localized to differentiated luminal epithelial cells (20)(21)(22).…”