CCR2 monocytes/macrophages drive steroid hormone imbalance-related prostatic fibrosis.

Benign Prostatic Hyperplasia (BPH) is a complex condition leading to Lower Urinary Tract Symptoms in aging men, characterized by cellular proliferation, smooth muscle dysfunction, inflammation, and fibrosis. While BPH is known to involve heightened macrophage infiltration, the specific contribution of infiltrating monocytes/macrophages to the disease mechanism remains uncertain. This research explores the impact of reducing circulating monocytes and subsequently limiting their tissue infiltration by using Ccr2 knockout (Ccr2-KO) mice.

Steroid hormone imbalance drives macrophage infiltration and Spp1/osteopontin foam cell differentiation in the prostate.

Benign prostatic hyperplasia (BPH) occurs progressively with aging in men and drives deteriorating symptoms collectively known as lower urinary tract symptoms (LUTS). Age-associated changes in circulating steroid hormones, and prostate inflammation have been postulated in the etiology of BPH/LUTS. The link between hormones and inflammation in the development of BPH/LUTS is conflicting because they may occur independently or as sequential steps in disease pathogenesis.

Osteopontin Deficiency Ameliorates Prostatic Fibrosis and Inflammation.

Fibrogenic and inflammatory processes in the prostate are linked to the development of lower urinary tract symptoms (LUTS) in men. Our previous studies identified that osteopontin (OPN), a pro-fibrotic cytokine, is abundant in the prostate of men with LUTS, and its secretion is stimulated by inflammatory cytokines potentially to drive fibrosis. This study investigates whether the lack of OPN ameliorates inflammation and fibrosis in the mouse prostate.

Fetal bisphenol A and ethinylestradiol exposure alters male rat urogenital tract morphology at birth: Confirmation of prior low-dose findings in CLARITY-BPA.

Bisphenol A (BPA) is a contaminant in virtually all Americans. To examine BPA's adverse effects, the FDA-NCTR, NIEHS, and 14 groups of academic scientists formed a consortium: CLARITY-BPA. The purpose of our study was to investigate the effects of a wide range of doses of BPA on fetal development of the NCTR CD-SD male rat urogenital sinus (UGS).

Prostate Transition Zone Fibrosis is Associated with Clinical Progression in the MTOPS Study.

Purpose: Medications targeting androgen receptor activity (eg finasteride) or smooth muscle contractility (eg doxazosin) do not resolve lower urinary tract symptoms indicative of lower urinary tract dysfunction in an important subgroup of men. Recently fibrosis has been implicated as another pathobiology contributing to male lower urinary tract symptoms but to our knowledge no systematic studies have been done to assess fibrosis in the context of medical treatment. We determine whether fibrotic changes in the prostate transition zone are associated with an increased risk of clinical progression in participants treated with doxazosin, finasteride or finasteride plus doxazosin in the MTOPS (Medical Therapy of Prostatic Symptoms) study.

Homozygous loss of mouse tetraspanin CD82 enhances integrin αIIbβ3 expression and clot retraction in platelets.

Integrin αIIbβ3 is critical for platelet-mediated blood clotting. Tetraspanins are well-established regulators of integrins and genetic loss of tetraspanin CD151 or TSSC6 in mice leads to increased bleeding due to inadequate integrin αIIbβ3 outside-in signaling. Conversely, mild but enhanced integrin αIIbβ3 activation and hyperaggregation is observed in CD9 and CD63 null mice respectively.

Estrogen receptor-α is a key mediator and therapeutic target for bladder complications of benign prostatic hyperplasia.

Purpose: Estrogens are important in prostate growth and have a role in benign prostatic hyperplasia. However, to our knowledge no current therapy directly targets estrogen action. Estrogens act primarily via estrogen receptors α and β.

Renal capsule xenografting and subcutaneous pellet implantation for the evaluation of prostate carcinogenesis and benign prostatic hyperplasia.

New therapies for two common prostate diseases, prostate cancer (PrCa) and benign prostatic hyperplasia (BPH), depend critically on experiments evaluating their hormonal regulation. Sex steroid hormones (notably androgens and estrogens) are important in PrCa and BPH; we probe their respective roles in inducing prostate growth and carcinogenesis in mice with experiments using compressed hormone pellets. Hormone and/or drug pellets are easily manufactured with a pellet press, and surgically implanted into the subcutaneous tissue of the male mouse host.