Developmental estrogenization and prostatic neoplasia

Santti, Risto; Rr, Newbold; Mäkelä, Sari; Pylkkänen, Liisa; Ja, McLachlan

doi:10.1002/pros.2990240204

Cited by 131 publications

(77 citation statements)

References 115 publications

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“…In prostate, it has been suggested that estrogens and their receptors may be involved in cancer development and progression (Santti et al 1994, Farnsworth et al 1999, Jarred et al 2000. Estrogen exposure during prostate development may initiate cellular processes resulting in future neoplasia (Santti et al 1994).…”

Section: Analysis Of Era and Erb Expression In Estrogen-sensitive Canmentioning

confidence: 99%

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Loss of ERβ expression as a common step in estrogen-dependent tumor progression

Bardin¹,

Boulle²,

Lazennec³

et al. 2004

Endocr Relat Cancer

386

308

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The characterization of estrogen receptor beta (ERb) brought new insight into the mechanisms underlying estrogen signaling. Estrogen induction of cell proliferation is a crucial step in carcinogenesis of gynecologic target tissues, and the mitogenic effects of estrogen in these tissues (such as breast, endometrium and ovary) are well documented both in vitro and in vivo. There is also an emerging body of evidence that colon and prostate cancer growth is influenced by estrogens. In all of these tissues, most studies have shown decreased ERb expression in cancer as compared with benign tumors or normal tissues, whereas ERa expression persists. The loss of ERb expression in cancer cells could reflect tumor cell dedifferentiation but may also represent a critical stage in estrogen-dependent tumor progression. Modulation of the expression of ERa target genes by ERb or ERb-specific gene induction could explain that ERb has a differential effect on proliferation as compared with ERa. ERb may exert a protective effect and thus constitute a new target for hormone therapy, such as ligand specific activation. The potential distinct roles of ERa and ERb expression in carcinogenesis, as suggested by experimental and clinical data, are discussed in this review.

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Section: Analysis Of Era and Erb Expression In Estrogen-sensitive Canmentioning

confidence: 99%

“…Estrogen exposure during prostate development may initiate cellular processes resulting in future neoplasia (Santti et al 1994). In a study of Latil et al (2001), ERa and ERb mRNA expression was quantified by real-time RT-PCR in both benign and malignant prostate.…”

Section: Analysis Of Era and Erb Expression In Estrogen-sensitive Canmentioning

confidence: 99%

Loss of ERβ expression as a common step in estrogen-dependent tumor progression

Bardin¹,

Boulle²,

Lazennec³

et al. 2004

Endocr Relat Cancer

386

308

View full text Add to dashboard Cite

show abstract

“…This relative increase in estradiol has been shown to directly stimulate extensive squamous metaplasia within the developing prostatic epithelium which regresses rapidly after birth when estrogen levels drop precipitously (25)(26)(27). Although the natural role for estrogens during prostatic development is unclear, it has been proposed that excessive estrogenization during prostatic development may contribute to the high incidence of BPH and prostatic carcinoma currently observed in the aging male population (28,29). African-American men have a two-fold increased risk of prostatic carcinoma as compared to their Caucasian counterparts and it has been postulated that this is related, in part, to elevated levels of maternal estrogens during early gestation in this population (30,31).…”

Section: Estrogen Imprinting Of the Developing Prostate: Fetal Basis mentioning

confidence: 99%

Developmental estrogen exposures predispose to prostate carcinogenesis with aging☆

Prins

Birch

Tang

et al. 2007

Reproductive Toxicology

207

162

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Prostate morphogenesis occurs in utero in humans and during the perinatal period in rodents. While largely driven by androgens, there is compelling evidence for a permanent influence of estrogens on prostatic development. If estrogenic exposures are abnormally high during the critical developmental period, permanent alterations in prostate morphology and function are observed, a process referred to as developmental estrogenization. Using the neonatal rodent as an animal model, it has been shown that early exposure to high doses of estradiol results in an increased incidence of prostatic lesions with aging which include hyperplasia, inflammatory cell infiltration and prostatic intraepithelial neoplasia or PIN, believed to be the precursor lesion for prostatic adenocarcinoma. The present review summarizes research performed in our laboratory to characterize developmental estrogenization and identify the molecular pathways involved in mediating this response. Furthermore, recent studies performed with low-dose estradiol exposures during development as well as exposures to environmentally relevant doses of the endocrine disruptor bisphenol A show increased susceptibility to PIN lesions with aging following additional adult exposure to estradiol. Gene methylation analysis revealed a potential epigenetic basis for the estrogen imprinting of the prostate gland. Taken together, our results suggest that a full range of estrogenic exposures during the postnatal critical period -from environmentally relevant bisphenol A exposure to low-dose and pharmacologic estradiol exposures -results in an increased incidence and susceptibility to neoplastic transformation of the prostate gland in the aging male which may provide a fetal basis for this adult disease.

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“…[14][15][16] A recent study with the hypogonadal mouse model also pointed to direct action in the prostate gland. 17) In rats, combined administration of E2 and T synergistically increases ventral prostate weight and continuous treatment results in the development of glandular hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

Estrogen enhancement of androgen‐responsive gene expression in hormone‐induced hyperplasia in the ventral prostate of F344 rats

et al. 2004

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It has been postulated that, in addition to the crucial role of androgens, estrogens may be involved in development of prostate hyperplasia and cancer. In rats, combined administration of estrogen and androgen synergistically increases ventral prostate weight, and continued treatment results in the development of glandular hyperplasia. Prostate adenocarcinoma can be induced by chemical carcinogens in rats, and estrogen given together with an androgen generally shortens the latent period or increases the incidence and/or multiplicity of carcinomas. However, the mechanisms responsible for these synergistic effects of estrogen and androgen are poorly understood. In the present study, we examined the combined effects of 17β β β β-estradiol (E2) and testosterone (T) on gene expression in an early stage of prostate hyperplasia in an F344 rat model. ERα α α α expression, which has been suggested to contribute to development of prostatic hyperplasia, was increased by the combined treatment with T and E2, while it was suppressed by T alone. Expression levels of two androgen-responsive genes, probasin and kallikrein S3, were increased in the ventral prostate of rats treated with T plus E2 for 4 weeks in a dose-dependent manner, while short-term treatment did not alter the expression. These results suggested that enhancing effects of E2 on transcription of androgen-responsive genes, as well as an increased level of ERα α α α may play roles in the synergistic effects of E2 on T-induced prostate hyperplasia. ndrogen plays a crucial role in development of benign prostatic hyperplasia (BPH) and prostate cancer (PC), but it has been postulated that estrogens may also be involved. In humans, BPH is known to be linked with both serum estrogen levels and urinary estrogen content.1, 2) Canine BPH is inducible by simultaneous administration of androstanediol and estradiol, 3) and in rats, administration of estrogen concomitantly with androgen promotes prostate growth. 4) Furthermore, combined estrogen and androgen treatment enhances prostate carcinogenesis in Noble rats and in chemical carcinogen-treated F344 rats.5, 6) Radioligand-binding assays and immunohistochemical studies with ERα antibodies have demonstrated the presence of ER in both BPH and prostate carcinomas, but with no apparent correlation between receptor levels and pathologic features.7) The discovery of ERβ has given rise to a new understanding of the physiological roles of ER. 8,9) In ERβ knockout mice, multiple hyperplastic foci are observed in the ventral prostate 10) and immunohistochemical studies in human prostate cancer have provided evidence of decreased ERβ expression in human BPH and PC. 11,12) These findings suggest that estrogen receptors are involved in regulating cell proliferation and in carcinogenesis in the prostate gland.In the present study, we examined the combined effects of 17β-estradiol (E2) and testosterone (T) on gene expression in an early stage of prostate hyperplasia in an F344 rat model. RNAs isolated from the ventral prostate tissue wer...

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Developmental estrogenization and prostatic neoplasia

Cited by 131 publications

References 115 publications

Loss of ERβ expression as a common step in estrogen-dependent tumor progression

Loss of ERβ expression as a common step in estrogen-dependent tumor progression

Developmental estrogen exposures predispose to prostate carcinogenesis with aging☆

Estrogen enhancement of androgen‐responsive gene expression in hormone‐induced hyperplasia in the ventral prostate of F344 rats

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