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The Role of Prolactin in the Prostatic Inflammatory Response to Neonatal Estrogen

Department of Urology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612

Address all correspondence and requests for reprints to: Gail S. Prins, Ph.D., Department of Urology, M/C 955, University of Illinois at Chicago, 820 South Wood, Chicago, Illinois 60612. E-mail: gprins{at}uic.edu.

Estrogen exposure in the neonatal rat has been shown to disrupt the normal morphology and development of the prostate gland. The response to this exposure is manifest in adulthood as epithelial dysplasia and chronic inflammation. This inflammatory response consists of infiltrating T-lymphocytes and macrophages, which is typically observed in chronic prostatitis in both rodents and humans. In our rat model, the developmental hormonal milieu is altered following estrogenization, resulting in transient hyperprolactinemia, which begins prepubertally (postnatal d 21) and persists throughout puberty. The purpose of this experiment was to determine the role of prolactin (PRL) in the altered phenotype of the adult rat prostate exposed to neonatal estrogen. Male Sprague Dawley rat pups (n = 104) were randomized at birth to receive oil or estradiol benzoate on postnatal d 1, 3, and 5. They were further randomized to receive bromocriptine (BrC) pellets or placebo at d 15. Animals were killed at d 90. Serum PRL and testosterone levels, prostate lobe, and hormone-dependent and immune-related tissue weights and histology were examined. Animals receiving BrC had significantly lower PRL levels at d 90, regardless of estrogen status. Prostate lobe and testicular weights were significantly reduced in estrogenized animals vs. controls, and BrC did not abate this response, indicating that growth inhibition is not mediated through hyperprolactinemia. Splenic and thymus weights were greater in estrogenized animals, and this was partially reversed with BrC. Neonatal estrogen exposure resulted in a marked infiltration of CD4+ and CD8a+ lymphocytes in the prostate gland, and this was partially reversed by concomitant BrC treatment. In contrast, the estrogen-induced macrophage infiltration of the prostate was not affected by PRL suppression. These findings indicate that prostatic inflammation and immune cell infiltration in the prostate gland of neonatally estrogenized rats is mediated through a PRL-dependent as well as a PRL-independent mechanism. As prostatic inflammation or prostatitis in humans is associated with benign prostatic hyperplasia and prostatic carcinoma, this animal model may provide mechanistic insight with regards to age-associated prostatic lesions.

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