Changes in gene expression of growth factors and their receptors during castration-induced involution and androgen-induced regrowth of rat prostates

Abstract

To find candidates for the mediator of the growth‐promoting action of androgen in rat prostates, the changes in the steady‐state levels of mRNAs coding for several growth factors and their receptors were examined by Northern blot analysis during castration‐induced involution, and subsequent regrowth induced by androgen in the ventral and dorsolateral lobes. The changes in the growth factor systems and a typical secretory protein in the ventral lobe were similar to, but more prominent than, those in the dorsolateral lobe, showing the higher androgen dependency of the ventral lobe. Among the growth factors and their receptors investigated, only epidermal growth factor (EGF) showed apparent positive androgen dependency: EGF mRNA content in the ventral lobe decreased to about 30% of the normal level within 24 hr after castration, and increased, attaining about 200–300% of the normal level 3–5 days after androgen administration to castrated rats. mRNAs coding for all other factors examined, i.e., transforming growth factor‐α (TGF‐α), EGF receptor, basic fibroblast growth factor (bFGF), keratinocyte growth factor (KGF), FGF receptor 1, TGF‐β1, TGF‐β type II receptor, hepatocyte growth factor (HGF), and c‐MET/HGF receptor, increased after castration in greater or lesser degree, and after a brief pause or a decrease some of them increased again attaining a second peak 3–5 days after androgen replacement. The second increase was evident in TGF‐α, EGF receptor, KGF, and c‐MET mRNAs. These results indicate the possibility that multiple growth factor‐receptor systems participate in the androgen‐dependent regrowth of castrated rat prostates. © 1996 Wiley‐Liss, Inc.

Effects of androgen manipulation on α1-adrenoceptor subtypes in the rat seminal vesicle

“…Thus, the temporal changes in a 1 -adrenoceptor subtype expression with surgical castration suggest that the sensitivity of the a 1 -adrenoceptor gene subtypes to testosterone or androgen-related factors is different. A number of mRNA transcripts studied during castration-induced involution and androgen-induced regrowth of tissues in the male reproductive system, including rat seminal vesicle, present complex and negative dependency on testosterone (Collins et al, 1988;Huang et al, 1997;Nishi et al, 1996). It is difficult to correlate the a 1 -adrenoceptor mRNA variations in seminal vesicle during androgen manipulation of the animals to a direct hormonal effect.…”

Differential effects of diabetes induced by streptozotocin and that develops spontaneously on prostate growth in Bio Breeding (BB) rats

“…Insulin treatment of diabetic rats normalized the changes in prostatic weight and serum testosterone levels, and reversed the alterations in TGF-β expression at protein and gene transcript levels to control levels (Ikeda et al, 2000). The STZ diabetes-induced changes in the growth factors are similar to those seen in castrated rats (Nishi et al, 1996;Desai and Kondaiah, 2000), suggesting that decreases in testosterone may contribute to the changes observed in diabetic rat prostate.…”

FGF signalling in prostate development, tissue homoeostasis and tumorigenesis

“…However, whether androgens directly regulate FGF7 and FGF10 expression remains controversial. In vitro prostate stromal cell cultures show that both FGF7 and FGF10 mRNA are up-regulated by treatment with testosterone [5,42]; however, observations in vivo indicate that FGF7 is decreased, rather than increased, in response to androgens [43] and the FGF10 mRNA level is not correlated with androgen exposure in prostate organ culture [6]. Whether there are AREs in the promoter regions of Fgf7 and Fgf10 genes remains to be identified.…”