Morphometric Analysis of the Rat Ventral Prostate and Seminal Vesicles during Prepubertal Development: Effects of Neonatal Treatment with Estrogen

Gaytan, F.; Bellido, C.; Aguilar, Rafaela; Lucena, M. C.

doi:10.1095/biolreprod35.1.219

Cited by 23 publications

(11 citation statements)

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“…In histological sections of the prostate, the stroma of neoDES mice was also very dense and had increased cellularity. Increased cell labelling in response to DHT may at least partially account for the increased relative volume of fibromuscular stroma revealed by morphometry in the present study as well as in another study on rat [16]. However, the role of inflammation which was present at the same prostatic sites and/or the decreased secretion which could result in smaller lumina in neoDES animals cannot be excluded as contributing to the increased stromal growth.…”

Section: Discussionmentioning

confidence: 99%

Regional differences in the prostate of the neonatally estrogenized mouse

et al. 1991

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Neonatal estrogenization of the mouse with diethylstilbestrol resulted in time-of-exposure and dose-dependent inhibition of the growth of the prostatic lobes observed at the age of 2 mon. The critical time was the days 1-6 of postnatal life. In neonatally estrogenized (neoDES) mice, responses to 5 alpha-dihydrotestosterone in terms of nuclear 3H-thymidine labelling were altered concomitantly with the inhibition of growth and were in accordance with changes in the relative volumes of epithelium, glandular lumina, and interacinar stroma. Secondary estrogen treatment of neoDES mice with 17 beta-estradiol did not increase 3H-thymidine labelling in the prostate of control or neoDES mice. However, it induced squamous epithelial metaplasia in periurethral collecting ducts and proximal parts of coagulating glands of neoDES animals. In control mice only slight epithelial hyperplasia could be observed after similar treatment. Estrogen receptors, located immunocytochemically in nuclei of stromal cell, corresponded with the sites of increased estrogen sensitivity, observed as metaplastic transformation. When the neoDES animals aged, epithelial hyperplasia and dysplasia could be observed at distinct prostatic sites, ie, the periurethral collecting ducts and the coagulating glands and periurethral glands, and stromal inflammation become more extensive. Almost identical location of the epithelial changes and the altered estrogen response is suggestive of causal relationship.

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Section: Discussionmentioning

confidence: 99%

Regional differences in the prostate of the neonatally estrogenized mouse

et al. 1991

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“…Exposure of experimental animals to estrogens during critical periods of development have been reported to lead to altered structure (Chung & MacFadden 1980, Gaytan et al 1986, Naslund & Coffey 1986, Zhao et al 1992, vom Saal et al 1997 and function (Higgins et al 1981, Prins et al 1993) of the prostate. Neonatal estrogens induce long-term modifications in the accessory sex glands of rodents including epithelial changes (Arai 1970, Pylkkanen et al 1991, changed hormonal sensitivity (Rajfer & Coffey.…”

Section: Introductionmentioning

confidence: 99%

Morphometric studies of neonatal estrogen imprinting in the mature mouse prostate

Singh

Handelsman²

1999

Journal of Endocrinology

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Estrogens play an important role in prostate physiology and neonatal exposure to estrogens has profound effects on the mature structure and hormonal sensitivity of rodent prostate. We aimed to determine the long-term effects of neonatal estrogens on the ductal architecture, morphology and hormonal sensitivity of the mature mouse prostate. Newborn mice (day 1-2) were administered a single injection (s.c.) of estrogens (estradiol benzoate (EB), diethylstilbestrol (DES)) with or without concomitant anti-estrogens (tamoxifen (TAM) or ICI 182 780 (ICI)) TAM or ICI alone, GnRH-antagonist (GnRH-A) or vehicle. At 7 weeks of age, ventral prostates (VP) were microdissected to estimate branch tip numbers and processed for stereologic analysis of volume fractions and diameters of various tissue components. Estrogens induced permanently reduced branching morphogenesis leading to reduced VP weights and these effects were fully reproduced by GnRH-A, consistent with an indirect effect. Stereologically, neonatal estrogens induced epithelial and stromal hyperplasia and significantly reduced (P<0·05) the diameters of VP glandular tubules and lumen compared with controls and these regressive effects were not reversed either by TAM or ICI. These studies confirm that a single neonatal dose of both DES and EB produces imprinting in the mature mouse prostate and indicate that neonatal estrogen effects involve both direct as well as indirect effects. In addition, both TAM and ICI act as partial agonists to the estrogen receptor in the ventral prostate of neonatal mouse.

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“…(Endocrinology 139: 874 -883, 1998) E XPOSURE of rats to exogenous estrogens during the neonatal period causes marked developmental abnormalities in the prostate gland and permanent alterations in its growth, secretory function, and activational response to androgens during adulthood (1)(2)(3)(4). A further significant increase in ER␤ message was observed at day 30, which indicates that full epithelial ER␤ expression may require the completion of functional differentiation.…”

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Estrogen Receptor-β Messenger Ribonucleic Acid Ontogeny in the Prostate of Normal and Neonatally Estrogenized Rats*

et al. 1998

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Neonatal exposure to estrogens permanently alters rat prostate growth and epithelial differentiation leading to prostatic dysplasia on aging. The effects are lobe-specific, with the greatest response observed in the ventral lobe. Recently, a novel estrogen receptor (ER) complementary DNA was cloned from the rat prostate and termed ER-beta (ER beta) due to its high homology with the classical ER alpha. The protein possesses high affinity for 17beta-estradiol, indicating that ER beta is an alternate molecule for mediating estrogenic effects. Importantly, ER beta messenger RNA (mRNA) was localized to rat prostatic epithelial cells, which contrasts with the stromal localization of ER alpha in the rat prostate. The present study was undertaken to determine the ontogeny of ER beta mRNA expression in the rat prostate lobes and to examine the effects of early estrogen exposure on prostatic ER beta expression. Male rat pups were given 25 microg estradiol or oil on days 1, 3, and 5; were killed on day 1, 3 (oils only), 6, 10, 30, or 90; and prostate lobes were frozen. Longitudinal sections were processed for in situ hybridization using an 35S-labeled antisense mRNA probe corresponding to a 400-bp EcoRI-AccI fragment in the 5' untranslated region of rat ER beta complementary DNA. Image analysis was used to quantitate silver grains. In addition, total RNA was isolated from the ventral prostate (VP) and used for semiquantitative RT-PCR. Results from in situ hybridization revealed that at birth, ER beta was equivalently expressed at low levels in both mesenchymal and epithelial cells in oil-treated rats. From day 1 onwards, expression in all stromal cells slowly and significantly declined, so that in the control adult prostate, stromal ER beta mRNA was slightly above background. In the oil-treated control rats, epithelial ER beta mRNA increased to moderate levels between days 6-10 in the VP and days 10-15 in the dorsal and lateral lobes as cells began differentiation and ducts lumenized. A further significant increase in ER beta message was observed at day 30, which indicates that full epithelial ER beta expression may require the completion of functional differentiation. By day 90, expression levels were maximal and similar between the lobes. RT-PCR substantiated this developmental increase in ER beta between days 1-90. Neonatal exposure to estrogens did not have an immediate effect on prostatic ER beta mRNA levels as determined by in situ hybridization and RT-PCR. However, the marked increase in epithelial cell expression at day 30 observed in the control VP was dampened in the VP of animals exposed neonatally to estrogens. By day 90, the VP of estrogenized rats possessed low ER beta message levels compared with the high expression in oil controls. In contrast, the dorsal and lateral lobes of neonatally estrogenized rats possessed high levels of ER beta mRNA at day 90, equivalent to controls. The present data demonstrate that ER beta mRNA expression in the rat prostate is developmentally regulated, and that neonatal estrogen...

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Morphometric Analysis of the Rat Ventral Prostate and Seminal Vesicles during Prepubertal Development: Effects of Neonatal Treatment with Estrogen

Cited by 23 publications

References 0 publications

Regional differences in the prostate of the neonatally estrogenized mouse

Regional differences in the prostate of the neonatally estrogenized mouse

Morphometric studies of neonatal estrogen imprinting in the mature mouse prostate

Estrogen Receptor-β Messenger Ribonucleic Acid Ontogeny in the Prostate of Normal and Neonatally Estrogenized Rats*

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