TY - JOUR
T1 - The effect of androgen, estrogen, and growth factors on the proliferation of cultured fibroblasts derived from human fetal and adult prostates
AU - Levine, Alice C.
AU - Ren, Meiyue
AU - Huber, Gerold K.
AU - Kirschenbaum, Alexander
PY - 1992/4
Y1 - 1992/4
N2 - Stromal enlargement plays a key role in the development of benign prostatic hypertrophy in humans. Human prostatic fibroblasts were obtained from fetal and adult prostates and characterized as to their androgen and estrogen receptor status and growth in response to dihydrotestosterone (DHT), estradiol (E2), hydroxyflutamide (OH-FLU), hydrocortisone, basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF). In addition, the ability of hormones and growth factors to induce the messenger RNA (mRNA) for the c-fos protooncogene was assessed as a measure of the early, direct effects of these compounds on cellular proliferation. Nuclear androgen receptors were demonstrable by immunocytochemistry in both fetal and adult cells. Nuclear estrogen receptor staining was negative. Neither E2 nor hydrocortisone increased cellular proliferation. Both EGF and bFGF did increase cellular growth. DHT (10-8-10-7 M) had a significant stimulatory effect on cell growth only in serum-free media. OH-FLU addition enhanced DHT induced proliferation. Changing the media during the course of the experiment obliterated the stimulatory effect of DHT. Both EGF (10 ng/ml) and bFGF (20 ng/ml) increased the mRNA for the c-fos protooncogene. DHT (10-7 M) did not induce the mRNA for c-fos. We conclude that EGF, bFGF, and DHT (especially in combination with OH-FLU) increase the proliferation of human prostatic fetal and adult fibroblasts in vitro. E2 has no effect on fibroblast proliferation. The stimulatory effects of EGF and bFGF are direct, whereas the effect of DHT appears to be indirect, possibly mediated via the increased production and/or secretion of growth factors.
AB - Stromal enlargement plays a key role in the development of benign prostatic hypertrophy in humans. Human prostatic fibroblasts were obtained from fetal and adult prostates and characterized as to their androgen and estrogen receptor status and growth in response to dihydrotestosterone (DHT), estradiol (E2), hydroxyflutamide (OH-FLU), hydrocortisone, basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF). In addition, the ability of hormones and growth factors to induce the messenger RNA (mRNA) for the c-fos protooncogene was assessed as a measure of the early, direct effects of these compounds on cellular proliferation. Nuclear androgen receptors were demonstrable by immunocytochemistry in both fetal and adult cells. Nuclear estrogen receptor staining was negative. Neither E2 nor hydrocortisone increased cellular proliferation. Both EGF and bFGF did increase cellular growth. DHT (10-8-10-7 M) had a significant stimulatory effect on cell growth only in serum-free media. OH-FLU addition enhanced DHT induced proliferation. Changing the media during the course of the experiment obliterated the stimulatory effect of DHT. Both EGF (10 ng/ml) and bFGF (20 ng/ml) increased the mRNA for the c-fos protooncogene. DHT (10-7 M) did not induce the mRNA for c-fos. We conclude that EGF, bFGF, and DHT (especially in combination with OH-FLU) increase the proliferation of human prostatic fetal and adult fibroblasts in vitro. E2 has no effect on fibroblast proliferation. The stimulatory effects of EGF and bFGF are direct, whereas the effect of DHT appears to be indirect, possibly mediated via the increased production and/or secretion of growth factors.
UR - http://www.scopus.com/inward/record.url?scp=0026517184&partnerID=8YFLogxK
M3 - Article
C2 - 1372243
AN - SCOPUS:0026517184
SN - 0013-7227
VL - 130
SP - 2413
EP - 2419
JO - Endocrinology
JF - Endocrinology
IS - 4
ER -