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Biomedical subjects

L L Ewing

Publications and source records attributed to L L Ewing.

At least 73 records · Page 4Linked to original sources
PubMed1983

Spontaneous benign prostatic hyperplasia in the beagle. Age-associated changes in serum hormone levels, and the morphology and secretory function of the canine prostate.

This paper is a cross-sectional study of spontaneous benign prostatic hyperplasia (BPH) in a single canine species. The effects of aging and hormonal changes on the growth, histology, and glandular secretory function of the canine prostate were studied in 42 male beagles ranging in age from 8 mo to 9 yr. The beagle prostate enlarges for at least 6 yr, whether normal or hyperplastic. In contrast, prostatic secretory function, determined by ejaculate volume and total ejaculate protein, declines markedly after 4 yr of age. These reciprocal growth and functional changes in the prostate are closely associated with a progressive increase in the incidence of BPH, which is already apparent in some dogs by age two. With age there is a modest decrease in serum androgen levels with no apparent change in serum 17 beta-estradiol levels. This suggests that the growth and functional changes that are associated with the development of BPH and are initiated very early in life reflect an altered sensitivity of the prostate to serum androgens or a response to the relative decrease in the serum androgen to estrogen ratio.

Aging↗
PubMed1983

Tissue content of dihydrotestosterone in human prostatic hyperplasis is not supranormal.

The dihydrotestosterone content of normal peripheral and benign hyperplastic prostates was measured in tissue obtained at open surgical procedures on 29 men of ages 36 to 82 yr. The dihydrotestosterone content in normal prostates (mean +/- SE, 5.1 +/- 0.4 ng/g tissue) and in benign hyperplastic prostates (5.0 +/- 0.4) was similar. In 11 patients in whom both normal and hyperplastic prostatic tissue was harvested simultaneously at the same operation, there was no significant difference in the content of dihydrotestosterone in the two types of tissue. These findings fail to confirm the widespread belief that dihydrotestosterone content is elevated in benign hyperplastic prostates. Our data differ from the reported literature in one major respect: the dihydrotestosterone content of normal peripheral prostate in this study is three to four times higher than previously reported. This difference between the present and earlier studies was resolved by experiments performed on cadavers, which were the source of normal prostatic tissue used by other investigators. Dihydrotestosterone content was measured in seven cadavers ranging in age from 19 to 82 yr of age. The results of this experiment indicate that the dihydrotestosterone content of prostatic tissue removed at autopsy is factitiously low (0.7-1.0 ng/g tissue). This finding was confirmed by in vitro incubations of fresh prostatic tissue at 37 degrees C that demonstrated reduction of dihydrotestosterone content to low levels within 2 h. When taken together, these results indicate that when prostatic tissue is harvested appropriately, the dihydrotestosterone content of normal peripheral and hyperplastic tissues is the same. This finding should influence future research into the etiology of benign prostatic hyperplasia.

Adult↗
PubMed1983

Effect of luteinizing hormone on Leydig cell structure and testosterone secretion.

Hypophysectomy or sc implantation of testosterone-estradiol 17 beta (T-E) filled polydimethylsiloxane capsules for 5 days caused a dramatic reduction in testosterone secretion when testes subsequently were perfused in vitro. The diminution in testosterone-secreting capacity of testes from T-E treated rats was coupled closely with reductions in the membrane surface areas of Leydig cell cytoplasmic organelles, particularly those of the smooth endoplasmic reticulum. Simultaneous treatment of T-E implanted rats with LH (12 micrograms/day), but not with FSH, PRL, TSH, or GH, maintained both the Leydig-cell cytoplasmic membranes and the capacity of testes to secrete testosterone in vitro. Testosterone secretion by testes from hypophysectomized rats treated simultaneously with T-E plus LH was identical to that in control rats. Therefore, T-E did not inhibit directly the Leydig cell steroidogenic apparatus. Taken together these results suggest that one of the trophic effects of LH in the Leydig cell is to maintained the integrity of smooth endoplasmic reticulum and enzymes responsible for the conversion of pregnenolone to testosterone.

Animals↗
PubMed1983

Dihydrotestosterone concentration of beagle prostatic tissue: effect of age and hyperplasia.

Dihydrotestosterone (DHT) concentration was measured in prostatic tissue obtained from castrate or intact beagles treated with androgens and/or estradiol-17 beta. Also DHT concentration was measured in prostatic tissue of beagles ranging from 0.7-9.2 yr; some with and others without spontaneously occurring benign prostatic hyperplasia (BPH). Three major results were forthcoming. First, a linear, positive correlation was observed between prostatic weight and DHT concentration in castrated or intact beagles treated with 11 of 15 steroid hormone regimens. Four additional treatments including intact or castrated beagles treated with either DHT or 5 alpha-androstan-3 alpha,17 beta-diol alone resulted in high concentrations of prostatic DHT but not equally high prostatic weight. Thus, prostatic DHT concentration is not always tightly coupled with prostate weight in the beagle. Second, there was no significant (P greater than 0.25) difference in prostatic DHT concentration between dogs with histologically normal prostates and those with spontaneous BPH. Thus, contrary to earlier reports, the tissue concentration of DHT in dog prostatic hyperplasia is not supranormal. Third, there was a dramatic change in prostatic DHT concentration which peaked at 3.8 yr. We conclude that steroid hormone treatment regimens which caused elevated prostatic DHT concentrations did not always result in equally high prostatic weight in the beagle. Also, if androgens like DHT are related causally to BPH in the dog, they probably play a permissive rather than an inductive role in the disease process.

Aging↗
PubMed1983

Oestrogen secretion by in-vitro perfused testes: species comparison and factors affecting short-term secretion.

Testes from mature rats, rabbits, hamsters, guinea-pigs and dogs were perfused in vitro with added gonadotrophins to study the qualitative and quantitative aspects of oestrogen secretion by these species. After separation by high performance liquid chromatography (HPLC), the major oestrogen secreted by the testes of all five species was oestradiol-17 beta; lesser amounts of oestrone were also detected for all species. Secretion rates of oestradiol and testosterone were determined for one testis from each of six animals of each species after purification by HPLC. Oestradiol and testosterone secretion varied (P less than 0.05) among species on both per testis and per gram of testis bases. The rabbit, which was a high secretor of oestradiol, was used in subsequent experiments to study the factors which affect short-term oestradiol secretion by perfused testes. Luteinizing hormone (NIAMDD-LH-S21) at 100 ng/ml significantly stimulated oestradiol secretion by 2.9-fold and increased testosterone secretion by 155-fold. Follicle-stimulating hormone (NIH-FSH-S11) had no significant effect on secretion of either steroid. In a time-course study in which LH stimulation was started after 45 min of control perfusion, the rates of increase in oestradiol and testosterone secretion over time were similar. Increasing amounts of testosterone added directly to the arterial perfusion medium (0-10 micrograms/ml) resulted in an increase in oestradiol secretion in the absence of gonadotrophins. Oestradiol secretion increased in a dose-dependent manner up to 1.0 microgram testosterone/ml; there was no further stimulation of oestradiol secretion at 10 micrograms testosterone/ml. When testes were perfused with saturating concentrations of testosterone (10 micrograms/ml) neither LH nor FSH at 100 ng/ml increased oestradiol secretion above control values. It appears that the major factor affecting oestradiol secretion by in-vitro perfused rabbit testes is the amount of substrate (testosterone) available for aromatization.

Animals↗
PubMed1982

Testicular atrophy associated with agenesis of the epididymis in the ACI rat.

The male ACI rat has a congenital Wolffian duct defect manifested by unilateral agenesis of the kidney, ureter, seminal vesicle, ductus deferens, and most of the epididymis. In the adult the testis on the affected side is markedly smaller than the contralateral testis and spermatogenesis is absent. In addition, in vitro perfusion of the affected testis revealed significantly less testosterone secretion than did the contralateral testis. Moreover, electron microscopy revealed that the smooth endoplasmic reticulum of the Leydig cell was significantly decreased. Thus, the affected testes clearly showed deranged spermatogenesis and Leydig cell structure and function. The ACI rat model may provide insight into the potential effects of congenital epididymal abnormalities on the testis of the human.

Animals↗
PubMed1981

Assessment of testicular testosterone production and Leydig cell structure.

Advances in two techniques have made the problem of assessing the acute and/or chronic effects of toxic agents on Leydig cell structure and testosterone synthesis and secretion amenable to study. First, in vitro testicular perfusion has been perfected to a point where it closely resembles in situ testosterone secretion. Second, now it is possible to quantify the proportion of Leydig cell cytoplasm occupied by the cellular organelles which contain steroidogenic enzymes. Herein, we report that inhibition of Leydig cell steroidogenic enzymes is reflected by reduced testosterone secretion by in vitro perfused rat and rabbit testes. Moreover, the activity of specific steroidogenic reactions can be monitored by measuring the secretion of reaction substrate(s) and product(s) from in vitro perfused testes. Testosterone secretion by in vitro perfused testes from five species is highly and positively correlated with the volume density of smooth endoplasmic reticulum in Leydig cell cytoplasm. Exploitation of these findings will allow toxicologists to quantitatively assess the effect of toxicants on Leydig cell testosterone biosynthesis and secretion, to identify the specific steroidogenic enzymes affected, to assess whether the membranous environment of the steroidogenic enzymes is compromised, and perhaps even to predict the deleterious effect of a toxic agent on Leydig cell steroidogenic function from a stereological assessment of Leydig cell ultrastructure.

Aging↗
PubMed1981

Serum levels of follicle stimulating hormone, luteinizing hormone, prolactin, testosterone, 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha, 17 beta-diol, 5 alpha-androstane-3 beta, 17 beta-diol, and 17 beta-estradiol from male beagles with spontaneous or induced benign prostatic hyperplasia.

The serum concentration of testosterone (T) 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol), 5 alpha-androstane-3 beta , 17 beta-diol (3 beta-diol), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin in young (less than 40 months) beagles with spontaneous benign prostatic hyperplasia (BPH) were not significantly (P greater than 0.25) different from serum hormone levels of age matched controls, or old (greater than 60 months) beagles with BPH. However, the serum hormone levels of age matched controls, or with BPH (2.46 +/- 0.51 pg per ml) was significantly (P less than 0.05) lower than that of age matched controls (3.93 +/- 0.35 pg per ml) and of old beagles with BPH is not associated with increased serum concentrations of androgens, or changes in serum levels of gonadotropins, but may be related to some change in estrogen biosynthesis or metabolism. In the second part of the experiment, castrate and intact beagles were treated for 4 months with three weekly injections of T, DHT, 3 alpha-diol, estradiol, T + estradiol, DHT + estradiol, or 3 alpha-diol + estradiol. As expected, the serum concentration of T, DHT, 3 alpha-diol, estradiol, LH, and FSH varied dramatically depending on the steroid regimen used. Analysis of these results showed that prostate weight was increased by steroid treatments which elevated the serum DHT concentration. However, glandular hyperplasia, indistinguishable from that seen in dogs with BPH, occurred only when estradiol was added to those steroid treatments which caused elevated serum DHT concentration.

Androgens↗
PubMed1980

Testosterone secretion by rat, rabbit, guinea pig, dog, and hamster testes perfused in vitro: correlation with Leydig cell ultrastructure.

Stereological methods were employed to determine volume and surface densities of cytoplasmic organelles in Leydig cells of hamster, rat, rabbit, dog, and guinea pig testes. Contralateral testes were perfused in vitro with maximally stimulating gonadotropin concentrations to determine the capacity of these testes to secrete testosterone. Significantly different amounts of testosterone were secreted by in vitro perfused testes of the five species when maximally stimulated with ovine LH. Significant differences also were seen in the volume and surface densities of smooth endoplasmic reticulum, mitochondria, rough endoplasmic reticulum, and lipids in Leydig cell cytoplasm of the five species. Most interestingly, linear positive correlations were seen between testosterone secretion and smooth endoplasmic reticulum volume (r = 0.99) and surface (r = 0.99) densities. Thus, virtually all of the differences in testosterone secretion by maximally stimulated testes of five species could be accounted for by between-species differences in the amount of Leydig cell smooth endoplasmic reticulum.

Animals↗
PubMed1979

Measurement of testosterone with a high-performance liquid chromatograph equipped with a flow-through ultraviolet spectrophotometer.

A technique is described for measuring nanogram amounts of testosterone using high-performance liquid chromatography with detection by a flow-through spectrophotometer. The addition of a non-radioisotopic internal standard (4-androsten-11 beta-ol-3,17-dione) to the biological specimen automatically corrects for testosterone losses due to extraction and non-quantitative sample injection into the high-performance liquid chromatograph. This new method, which can be performed by inexperienced personnel, is shown to be rapid, precise, accurate and specific for testosterone.

Animals↗
PubMed1979

Celite column chromatography followed by reversed-phase high-performance liquid chromatography: a simple, two-step method for separating 14 testicular steroids.

The separation of 14 major testicular steroids has been effected by a simple, two-step procedure involving Celite column chromatography followed by reversed-phase high-performance liquid chromatography. The technique does not alter the resolved steroids, which are then available for subsequent analysis.

Chromatography, High Pressure Liquid↗