BPH Chirurgie Rohr

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While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. However, BPH is a multifactorial disease and not all men respond well to currently available treatments, suggesting factors other than androgens are involved. The prostate is an estrogen target tissue and estrogens directly and indirectly affect growth and differentiation of prostate. The precise role of endogenous and exogenous estrogens in directly affecting prostate growth and differentiation in the context of BPH is an understudied area.

Estrogens and selective estrogen receptor modulators SERMs have been shown to promote or inhibit BPH Chirurgie Rohr proliferation signifying potential roles in BPH. Recent research has demonstrated that estrogen receptor signaling pathways may be important in the development and maintenance of BPH and LUTS; BPH Chirurgie Rohr, new models are needed to genetically dissect estrogen regulated molecular mechanisms BPH Chirurgie Rohr in BPH.

Benign prostatic hyperplasia BPH also commonly called benign prostatic hypertrophy BPH Chirurgie Rohr be described clinically or pathologically. Clinical BPH is commonly viewed as benign enlargement of the prostate, which contributes to an array of urinary voiding difficulties that can range from bothersome to significantly impacting quality of BPH Chirurgie Rohr among older men [ 1 ]. Pathologic BPH is the histological determination of non-neoplastic new prostatic growth in adult men.

The high prevalence of BPH in older men has led some to consider prostatic hyperplasia to be a ubiquitous result of aging [ 3 ]. The precise molecular mechanisms underlying the induction, maintenance, and development BPH Chirurgie Rohr clinical sequelae resulting from BPH are incompletely understood. This article will review the BPH literature and consider the widely accepted permissive role of androgens and the emerging importance of estrogens in BPH.

A greater understanding of sex steroid signaling in BPH will be necessary for novel and effective prevention and treatment strategies for this very common clinical problem. The human prostate consists of three distinct histologic zones: central, peripheral, and transition [ 4 ]. While prostate cancer is found primarily in the peripheral zone, nearly all clinically significant BPH develops in the transition zone of the prostate [ 5 ].

Macroscopic growth of the transition zone can cause narrowing of the urethra as it passes through the prostate, leading to a bladder outlet obstruction BOOwhich may affect the flow of urine. In men the prostate is the most common cause of obstruction. BPH and subsequent BOO contributes to a spectrum of urinary voiding problems that can significantly impact quality of life and are commonly known as lower urinary tract symptoms LUTS [ 6 ]. In large studies of men with BPH BPH Chirurgie Rohr LUTS, there is not a strong correlation between prostate size, symptoms BPH Chirurgie Rohr urinary flow rates [ 1 ].

However, serum prostatic specific antigen PSA does correlate BPH Chirurgie Rohr prostate volume, and men with larger prostates and high serum PSA are at higher risk of experiencing more significant symptoms, including ultimate progression to acute urinary retention [ BPH Chirurgie Rohr ]. LUTS include bladder storage symptoms such as nocturia, urgency, increased urinary frequency, and difficulty starting the stream of urine; decreased urinary flow and incomplete emptying are generally attributed to problems with bladder emptying [ 7 ].

Other important causes and contributing factors to LUTS are age-related declines in detrusor function and systemic medical conditions [ 78 ]. Experiencing an acute episode of urinary retention and nocturia are clinical markers of increased mortality risk that likely represent the high comorbidity of BPH with other systemic medical conditions [ 910 ]. A number of treatment options exist for the care of men with bothersome LUTS due to an enlarged prostate. Alpha-1 adrenergic receptors are present throughout the smooth muscle of the male urinary tract, and at the level of the spinal cord, ganglia and nerve terminals, and therefore, are likely to have a wide spectrum of favorable effects on these extra-prostatic sites [ 11 ].

The gold-standard treatment for BPH is transurethral resection of the prostate TURP which relieves obstruction by removing BPH nodules in the BPH Chirurgie Rohr zone; however, a variety of minimally BPH Chirurgie Rohr surgical approaches exist [ 6 ]. Some patients do not respond well to these standards of care BPH Chirurgie Rohr it is difficult to predict which patients will respond to a particular treatment.

Thus, there remains a need for advances and improvements in treatment and prevention of BPH and LUTS based on a better understanding of their pathophysiology. Pathological BPH is characterized by hyperplastic epithelial and stromal growth that coalesces into microscopic and macroscopic nodules in the prostate gland [ 13 ].

There are five generalized types of BPH nodules: 1. Fibromyoadenomatous common2. Fibroadenomatous, 3. Fibromuscular, and 5. Muscular uncommon [ 14 ]. More commonly BPH is described as epithelial containing mostly prostate epithelial cellsmixed containing BPH Chirurgie Rohr and epithelial cellsBPH Chirurgie Rohr stromal containing only BPH Chirurgie Rohr cells [ 15 ]. The earliest nodules that develop in BPH are found in the periurethral region and are typically stromal, composed of BPH Chirurgie Rohr tissue mixed with some smooth muscle [ 16 ].

Somewhat less commonly, BPH nodules may be found in the peripheral zone, which may be palpable with digital rectal examination, and are typically composed of epithelial glandular elements [ 17 ]. The lack of glandular elements in stromal BPH nodules, and the observation of zonal differences in the inception of BPH nodules suggest a distinct etiology of stromal nodules compared to BPH with glandular components.

When the transition BPH Chirurgie Rohr enlarges macroscopically, due to BPH nodular growth, it can impede the flow of urine through the prostatic urethra and hence contribute to LUTS. Understanding the key molecular mechanisms for how distinct BPH nodules develop and are associated with LUTS is essential to developing clinical management tools for these diseases. The precise molecular etiology of BPH is complicated and unknown, but several theories have been proposed.

These include embryonic reawakening, aging, androgens, estrogens, oxidoreductase, and inflammation theories [ 1819 ]. One prominent theory of BPH pathogenesis was proposed by McNeal and is termed the embryonic reawakening theory [ 5 ]. InMcNeal posited that prostatic hyperplasia represents an awakening of hormonally-mediated developmental processes [ 5 ]. Consistent with this observation, Cunha demonstrated that androgen regulation and paracrine interactions were necessary for prostate glandular development and maintenance, establishing the key role of stromal-epithelial cell interactions in the prostate [ 20 — 23 ].

A hormonal etiology involving dysregulation of stromal-epithelial cell interactions is recognized as important for BPH development, but the precise pathogenesis remains to be elucidated.

All of the proposed theories BPH Chirurgie Rohr require the presence of androgens; however, androgens appear to be permissive but not inductive reviewed by [ 3 ]. Age is an associated factor for the development of both histologic and clinically significant BPH. Furthermore, younger men develop BPH but at much lower rates compared to aged men [ 2 ].

As noted above, there are different types of BPH nodules, BPH Chirurgie Rohr are likely to be initiated by different molecular mechanisms and as such multiple BPH Chirurgie Rohr may explain the distinct types of BPH. Improved understanding of mechanisms of sex steroid hormone action in the induction and maintenance of BPH could lead to rational design of BPH Chirurgie Rohr targeted therapies. There are many in vitro and in vivo models of BPH and as with all model systems each has its own strengths and weaknesses Table 1 [ 24 ].

Perhaps the best organism to evaluate BPH is man; after all it is man whom all other models emulate. However, there are ethical issues that make human BPH studies difficult. Additionally, human genetics are highly variable between populations with distinct rates of BPH e. African American, Caucasian, and Asian making interpretation of key molecular events associated with the disease difficult. Another confounding issue in man as an experimental unit is the lack of ability to control the experimental environment.

Unlike in animal studies of lower BPH Chirurgie Rohr where temperature, lighting, housing, air, water, and food are tightly regulated, controlling the environment is challenging in human studies.

This is due in part to different socioeconomic backgrounds, personal choices, beliefs, and lifestyles. Finally, the cost associated with human research is high. For these reasons and others, use of humans are not ideal for early stages of BPH research.

Although BPH Chirurgie Rohr are inherent problems with human experimental studies of BPH, biological and genetic processes may be inconsistent among species and as such use of human cells and tissues are advantageous.

For example, prostatic PSA and adrenal androgens such as DHEA are not present in rodents, yet they are important in androgen action and prostate research. This has led a number of researchers to utilize human cells or tissues in BPH BPH Chirurgie Rohr. Specifically, human xenografts [ 25 — 27 ] BPH Chirurgie Rohr human tissue recombination xenograft models [ 28 ] have been developed and studied extensively. The use of xenografts is particularly well suited for studies evaluating maintenance or treatment of BPH, however with all xenograft studies several drawbacks apply.

They are less suitable for researching the development and prevention of BPH. Additionally, use of immunocompromised mouse or rat hosts make xenograft studies less appealing for evaluating BPH in the context of an intact immune system.

BOO is not possible with xenograft models. Tissue recombination, a technique that utilizes epithelia and stroma from various species or organs, has successfully been used for the study of a wide range of normal BPH Chirurgie Rohr pathogenic states [ 212229 — 33 ].

In this regard, Barclay and colleagues utilized tissue recombination methods using benign human prostatic epithelial cells BPH-1 cell line [ 34 ] and human stroma from BPH BPH Chirurgie Rohr normal prostates [ 28 ].

In those experiments it was found that BPH stroma significantly increased epithelial proliferation relative to control normal stroma, but importantly, malignant transformation did not occur in the BPH tissue recombinants [ 35 ]. These data are consistent with the important growth promoting role of stroma in BPH. There are distinct advantages of utilizing tissue recombination technology in BPH research.

First, human cells can be employed; second, cells are commonly grown in culture first and then recombined and grown in mouse hosts. While the cells are in culture it is possible to manipulate gene expression e.

Furthermore, in vitro experiments can be inexpensively performed as proof of principle prior to in vivo experiments. Lastly, tissue recombination is especially useful in evaluation of stromal-epithelial interactions, which are likely to play a central role in the manifestation and maintenance of BPH.

Models where spontaneous BPH occur are highly desirable because they likely recapitulate the underlying pathophysiology of human disease. The BPH Chirurgie Rohr animals other than man that develop spontaneous BPH are dogs [ 36 ] and nonhuman primates [ 3738 ]. The logistics and costs of carrying out such experiments with these species are typically high, and as such they are used less frequently.

Another limitation of spontaneous models is a lack of genetic manipulation, which restricts the use of these models for key mechanistic questions. Men as they age develop an increased estrogen to androgen ratio [ 39 ] coincident with the development of BPH.

This concept has led to hormone induction models of BPH. Like man, dogs and rodents have hormone responsive prostates making BPH Chirurgie Rohr particularly important in BPH research.

The administration of androgens and estrogens to recreate BPH Chirurgie Rohr hormonal environment similar to men as they age, reliably produces prostatic growth in dogs [ 2436BPH Chirurgie Rohr — 46 ] and rats [ 4748 ].

Key research utilizing these models have significantly moved the field of BPH research forward although prostate anatomy in dogs and rats differs significantly from the human prostate. In particular, these prostates may grow outwardly and away from the prostatic urethra, making prostatic growth less likely to cause obstruction and affect urine flow, a key feature of human BPH.

Nonetheless, obstructive voiding has been described in the dog [ 49 ]. Interestingly, encapsulating the canine prostate with a physical mesh wrapping to prevent outward expansion of the prostate leads to BOO [ 50 ]. Possibly the biggest obstacle to the utilization of many BPH Chirurgie Rohr models is the lack of genetic manipulation.

BPH Chirurgie Rohr ability to alter the genetics of cells, tissues, and whole organisms have greatly advanced the scientific understanding of molecular mechanisms in developmental biology, cancer, and many other disciplines. Although transgenic rats and dogs are possible [ 5152 ] they are unlikely to surpass the mouse in availability of genetically altered pathways.

Further complications with the usage BPH Chirurgie Rohr dog and rat hormone induction models are the associated cost and special housing needed for these studies.

Taken together anatomic differences, limitations of transgenic technology, and high cost have made the use of dogs and rats in BPH research less BPH Chirurgie Rohr. Perhaps the best genetically workable organism for BPH Chirurgie Rohr and BOO research is the mouse, in which gain and loss of function are easily regulated.

In general, mouse models for BPH have been poorly received due to their prostatic anatomy which is similar to the rat; therefore, the challenges of modeling human BPH are similar to those encountered with rats and dogs.

The prostatic lobes of the mouse, although hormonally responsive, grow outwardly from the urethra into the abdominal cavity. BPH Chirurgie Rohr an era where genomic information is freely available and genetic alterations are easily attained, it would be beneficial BPH Chirurgie Rohr have genetically tractable models and hence utilize the power of mouse genetics in BPH research.