FIGURE 1.

Schematic representation of steroid receptor expression in postnatal day 5–10 developing prostates from oil-treated control rats (A) and neonatally estrogenized rats (B). In the normal developing prostate (A), androgen receptor (AR) is the dominant steroid receptor in both epithelial and stromal cells. Under the influence of androgens, the stromal cells produce and secrete specific paracrine factors that dictate growth and differentiation of the gland. As epithelial cells differentiate, AR levels markedly increase and ERβ expression is induced. Other steroid receptors are expressed in a cell-specific manner and regulate cell-specific gene expression during critical developmental windows. Estrogen receptor α (ERα) is expressed at low levels in periductal stromal cells in the proximal region of the elongating ducts. RARβ is expressed in a subpopulation of basal epithelial cells, whereas RARα and γ are localized to periductal stromal cells along the ductal length. RXRα and RXRγ are expressed by basal cells, while RXRβ localizes to periductal stromal cells. Following a brief exposure to high levels of estrogens during the neonatal critical period, the prostatic steroid receptor profile is drastically altered (B). AR is absent in epithelial cells and is present at very low levels in stromal cells, thus dampening the androgen signaling pathway in the developing prostate. ERα is upregulated and expressed at high levels in periductal stromal cells along the length of the ducts, and progesterone receptor (PR) is induced in those same cells under the influence of estrogen. The number of cells expressing RARα and RARβ is markedly increased. Thus, estrogen exposure has switched the developing prostate from an androgen-dominated tissue to one that is regulated by estrogen, progesterone, and retinoids.