Proliferative disorders of the aging human prostate: involvement of protein hormones and their receptors.
The majority of elderly men is affected by benign and malignant diseases of the prostate. Both proliferative disorders, i.e., benign hyperplasia of the prostate (BPH) and prostate cancer (PCa)-which has recently emerged as the most common male malignancy in industrialized countries-seem to be governed by endocrine factors such as sex steroid hormones, but auto/paracrine factors are involved as well. Age-related changes in levels and ratios of endocrine factors as androgens, estrogens, gonadotropins, and prolactin (PRL) and changes in the balance between auto/paracrine growth-stimulatory and growth-inhibitory factors such as insulin-like growth factors (IGFs), epidermal growth factor (EGF), nerve growth factor (NGF), IGF-binding proteins (IGFBPs), and transforming growth factor beta (TGFbeta) are meant to be responsible for abnormal prostatic growth. We investigated the existence of putative local regulatory circuits involving the protein hormones, human growth hormone (hGH), human placental lactogen (hPL), and hPRL, and their corresponding receptors in prostatic tissue specimens (transurethral resections of the prostate, TURP; n = 11), in the prostatic cancer cell lines PC3, Du145, LnCap, a virus-transformed BPH cell line (BPH-1), and in a normal healthy prostate by RT-PCRs and highly specific and sensitive immunofluorometric assays (IFMA). Neither hPRL nor hGH was detected at the mRNA or protein levels in prostatic tissue and cell lines, with the exception of 2 of 11 prostatic TURP-samples, which showed weak expression of the PL-A/B genes. PRL- and GH-receptors were expressed in all normal and pathological prostatic specimens. Surprisingly, PRL-receptor expression was not detectable in prostatic cancer cell lines. The trophic effects of exogenous hGH, hPL, and hPRL were investigated by cell proliferation assays (WST-I) in prostatic primary cell cultures and PCa cell lines. hGH significantly (p < 0.005) increased cell proliferation up to 138+/-3.2% (1 nM hGH), while hPL and hPRL revealed only moderate effects. Our data suggest that local auto/paracrine networks of protein hormone actions are not involved in the pathology of BPH or prostatic cancer. On the other hand, systemic pituitary-derived hGH can increase the proliferative response of BPH and PCa, acting directly on the target organ prostate, via the hGH-R. In this case, envisaged GH substitution in elderly people must be viewed at with caution because age-related declines in GH/IGF-I could act as a protective mechanism against abnormal cell growth.
Untergasser
G
G
Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Innsbruck.
Rumpold
H
H
Hermann
M
M
Dirnhofer
S
S
Jilg
G
G
Berger
P
P
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D006728:Hormones / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D019382:Human Growth Hormone / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010928:Placental Lactogen / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011388:Prolactin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D006728:Hormones; D011956:Receptors, Cell Surface; D019382:Human Growth Hormone; D011388:Prolactin; D010928:Placental Lactogen