In this study we report the prevalence and growth rate of human benign prostatic hyperplasia with age by combining and analyzing data from 10 independent studies containing more than 1,000 prostates. The normal prostate reaches 20 plus or minus 6 gm. in men between 21 and 30 years old, and this weight remains essentially constant with increasing age unless benign prostatic hyperplasia develops. The prevalence of pathological benign prostatic hyperplasia is only 8 per cent at the fourth decade; however, 50 per cent of the male population has pathological benign prostatic hyperplasia when they are 51 to 60 years old. The average weight of a prostate that is recognized at autopsy to contain benign prostatic hyperplasia is 33 plus or minus 16 gm. Only 4 per cent of the prostates in men more than 70 years old reach sizes greater than 100 gm. An analysis of a logistic growth curve of benign prostatic hyperplasia lesions removed at prostatectomy indicates that the growth of benign prostatic hyperplasia is initiated probably before the patient is 30 years old. The early phase of benign prostatic hyperplasia growth (men between 31 and 50 years old) is characterized by a doubling time for the tumor weight of 4.5 years. In the mid phase of benign prostatic hyperplasia growth (men between 51 and 70 years old) the doubling time is 10 years, and increases to more than 100 years in patients beyond 70 years old.

The objective of this study was to determine whether postnatal increases in rat Leydig cell number result from differentiation of precursor cells, division of existing Leydig cells, or both. Our approach was 1) to examine changes in the absolute number of Leydig cells and potential precursor cells (macrophages, pericytes, and mesenchymal, endothelial, and myoid cells) per testis on day 19 of gestation (day -2) and days 7, 14, 21, 28, and 56 postpartum; 2) to examine the frequency with which mesenchymal and Leydig cells divide during prenatal and postnatal development; and 3) to identify and examine the fate of the progeny of Leydig and mesenchymal cell divisions during prenatal and postnatal development. Stereological methods were used to show that mesenchymal cells comprised 44% of the total interstitial cell population and Leydig cells 16% on day -2, whereas by day 56 postpartum the relationship had reversed; mesenchymal cells comprised 3% and Leydig cells 49%. These results suggested a precursor-product relationship between mesenchymal and Leydig cells because no such reciprocal relationship was observed between Leydig cells and macrophages, pericytes, endothelial, or myoid cells. Autoradiographic analysis of [3H]thymidine incorporation into mesenchymal and Leydig cells was consistent with this interpretation. In a series of pulse-chase experiments, the percentage of labeled mesenchymal and Leydig cells was measured after a single injection of [3H]thymidine on days 2, 14, 28, and 56 postpartum, each followed by sampling at timed intervals (between 1 h and 14 days) thereafter. Starting on day 14, the percentage of labeled Leydig cells was approximately 1% immediately after injection of [3H]thymidine and increased significantly to approximately 6% by 6 days after injection. No such increase was observed when rats were similarly injected starting on days 2, 28, and 56 postpartum. The rise in Leydig cell labeling between days 14 and 28 postpartum did not result in a decline in the number of silver grains over labeled Leydig cell nuclei, indicating that the increase in the percentage of labeled cells was not caused by Leydig cell division. These observations led us to conclude that the increase in Leydig cell labeling from days 14 to 28 was the result of recruitment from a compartment of labeled mesenchymal cells. In contrast, our analysis indicated that from day 28 postpartum and thereafter until the mature number of Leydig cells is attained, Leydig cells are generated by division of morphologically recognizable Leydig cells.

Adult anesthetized male rats were submitted to in vivo micropuncture of the seminiferous and epididymal tubules and reproductive tract vasculature to obtain fluids for analysis of testosterone, 5 alpha-dihydrotestosterone, and androgen-binding protein (ABP). Androgen and ABP concentrations were determined by RIA. The highest concentrations of testosterone (73.14 +/- 5.12 ng/ml) were in testicular interstitial fluid. A significant downhill concentration gradient exists between testosterone concentrations in testicular interstitial fluid and seminiferous tubule fluid (50.24 +/- 2.26 ng/ml); another significant decrease occurs between seminiferous tubule fluid and rete testis fluid (17.85 +/- 2.11 ng/ml). 5 alpha-Dihydrotestosterone concentrations were highest in intraluminal caput epididymidal fluids (58.73 +/- 6.48 ng/ml) as were ABP concentrations (33.30 +/- 2.40 mu leq/microliter). Intraluminal sperm concentrations were also determined, and from these data, fluid reabsorption by the efferent ducts and epididymal tubules were calculated. Eighty-nine percent of the fluid leaving the testis is reabsorbed between the rete testis and caput epididymidis, and 96% is reabsorbed between rete and cauda. It was calculated that large losses of androgen and ABP also occur from the lumen of the excurrent duct system. These losses may be due to metabolism, diffusion from the lumen, or uptake by cells.