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Biomedical subjects

L L Ewing

Publications and source records attributed to L L Ewing.

At least 55 records · Page 3Linked to original sources
PubMed1987

Biological markers of male reproductive toxicology.

Reproduction is a complex, stepwise series of processes that begins with gametogenesis, continues through gamete interaction, implantation, embryonic development, growth, parturition, and postnatal adaptation, and is completed with the development and sexual maturation of the newly formed organism. These reproductive processes do not take place in a chemically pristine environment, but rather in an environment increasingly contaminated with the products and by-products of the chemical age in which we live. Some environmental pollutants are known to be carcinogenic, mutagenic, or toxic to the reproductive system, but most have not been adequately tested for reproductive toxicity. Just as reproduction is complex, biological mechanisms underlying toxicology are similarly complex and involve absorption, distribution, metabolism (toxification and/or detoxification), excretion, and repair. The synthesis of these sciences into the relatively nascent science of reproductive toxicology includes teratology, pharmacology, epidemiology, and occupational and environmental health. Female reproductive function (especially pregnancy outcome) has historically been the focus of attention, but there is increasing interest in the effects of chemical exposure on male reproductive function. Several reports have documented the physiology, biochemistry, and toxicology of male mammalian reproduction, and evaluated susceptibility of the male to the effects of exogenous chemicals.

Animals↗
PubMed1986

Effect of age, castration, and testosterone replacement on the development and restoration of canine benign prostatic hyperplasia.

An experiment was designed to test the effect of castration and testosterone replacement on the development of benign prostatic hyperplasia (BPH) in young and on the restoration of BPH in old beagles. Twenty beagles were divided by age into young (1.5-2.5-yr) and old (6.0-8.5-yr) groups. Each of these groups was further divided randomly into two additional groups of age-matched, intact, untreated control and castrate beagles. The latter were then treated with testosterone-filled Silastic implants designed to clamp serum testosterone at concentrations similar to those observed in adult beagles for 7 months beginning 5 months after castration. Histopathologic characterization of each prostate was completed on biopsy material obtained at the beginning and end of the experiment. Prostate weights were determined each month for 12 months via a noninvasive two-dimensional X-ray procedure. Testosterone treatment for 7 months allowed BPH to develop in young and restored BPH in old beagles. These results suggest that testosterone in the adult beagle acts permissively to allow BPH to develop in the prostate of the aging dog. Some other testicular product may be required for the continued growth of BPH in aged beagles.

Age Factors↗
PubMed1986

Effects of aging on prostate growth in beagles.

Statistical analysis of 82 variables was completed to determine the effects of aging in the male beagle on prostatic growth and function. The results indicate that prostate weight increased to 4 yr and then reached a plateau. Prostatic secretory function (measured as ejaculate volume) followed a course different than the growth of the gland. Prostatic function increased and reached a peak at 4 yr and then declined abruptly. Therefore, there is a separation of the growth and secretory function of the canine prostate after 4 yr of age. Multiple linear regression analysis was performed to determine the mathematical relationship of these variables in predicting prostate weight and therefore benign prostatic hyperplasia, which is correlated with weight. The testicular secretion of testosterone and aging were paramount factors in predicting prostate weight. There appears to be an increased sensitivity of the prostate to testosterone secretion with advancing age.

Aging↗
PubMed1986

Short term androgen production by rat ovarian follicles and long term steroidogenesis by thecal explants in culture.

To characterize the aromatizable and 5 alpha-reduced androgens produced by developing ovarian follicles, small antral (SA) and preovulatory (PO) follicles, theca and granulosa cells were incubated for 4 h with or without 8-bromo-cAMP and androstenedione. In addition, thecal explants were cultured for 10 days with or without ovine LH (oLH) to determine if the hormone-induced changes in androgen synthesis by developing follicles could be mimicked in vitro. Short term incubations of SA and PO follicles, theca and granulosa cells in medium alone resulted in limited accumulation of androgen [testosterone, 5 alpha-androstan-17 beta-ol-3-one (DHT), 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha diol), and androsterone], as determined by RIA. In the presence of 8-bromo-cAMP, PO follicles produced large quantities of testosterone (3 ng), DHT (1 ng), 3 alpha diol (15 ng), and androsterone (14 ng), while SA follicles accumulated much less androgen (0.69, 0.05, 1.23, and 1.3 ng, respectively). In the presence of androstenedione and 8-bromo-cAMP, both SA and PO follicles and theca produced large amounts of aromatizable and 5 alpha-reduced androgens. SA and PO granulosa cells required the presence of the substrate androstenedione to produce androgens, primarily testosterone and 3 alpha diol. Therefore, progesterone, androstenedione, and 5 alpha-reduced androgens were used to monitor LH action on thecal cell function in culture. Small antral theca cultured in basic culture medium alone (containing 10% fetal calf serum) displayed an increased ability to accumulate androstenedione by day 6, approximately 3 times that observed on day 2. However, a 5-fold further increase in androstenedione accumulation was observed by day 6 for SA theca cultured in the presence of oLH. Maintenance of progesterone accumulation by SA theca throughout the culture period also was dependent on the presence of LH. In contrast, androstenedione accumulation by PO theca required the presence of LH in the culture medium, while progesterone accumulation in these cultures did not. Little or no 5 alpha-reduced androgen accumulated in the media of SA and PO theca cultured in basic culture medium alone. However, SA and PO theca cultured with oLH accumulated approximately 1 ng androsterone by day 10. We conclude that 1) SA and PO follicles, theca and granulosa cells possess the enzymes required to produce large amounts of 3 alpha diol and androsterone; 2) low concentrations of oLH are required to stimulate SA thecal steroidogenesis and to maintain PO thecal androstenedione accumulation in culture.(ABSTRACT TRUNCATED AT 400 WORDS)

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1985

Methods for monitoring canine prostate size: internal and external caliper measurements.

A method has been developed that allows the generation of a three-dimensional representation of the canine prostate from a pair of orthogonal radiographs. This information can be used to externally measure the length, width, and height of the prostate and from these results to calculate prostate weight. This externally estimated prostate weight is correlated closely (r = 0.90) with the actual prostate weight. The ability to generate an external caliper measurement of prostate weight will facilitate future studies of the effect of aging and hormonal manipulation on the canine prostate.

Aging↗
PubMed1985

Successful percutaneous balloon valvuloplasty of the aortic valve in an infant.

Percutaneous balloon aortic valvuloplasty was attempted in an eight-month-old infant with severe aortic valve stenosis. The procedure resulted in a fall in the resting transvalvular systolic pressure gradient from 106 mmHg to 40 mmHg and no aortic regurgitation. Clinical and Doppler echocardiography findings suggest persistent improved status 3 1/2 months after the procedure.

Angioplasty, Balloon↗
PubMed1985

Androgens in male rat reproductive tract fluids: hypophysectomy and steroid replacement.

The control of androgen concentrations in the intraluminal fluids of the male reproductive tract is not well understood. The present experiments were performed to determine the effects of hypophysectomy, hypophysectomy plus testosterone (T), and hypophysectomy plus pregnenolone treatment on intraluminal androgen concentrations in the adult rat testis and epididymis. T and 5 alpha-dihydrotestosterone (DHT) concentrations were determined in the vascular, interstitial, and intraluminal compartments of the epididymis. Testicular and epididymal morphology also were examined under light microscopy. Hypophysectomy of at least 5 days duration significantly reduced T and DHT concentrations in serum, tissues, and intraluminal fluids of the reproductive tract. T replacement for 14 days, which produced peripheral T concentrations of 5 ng/ml, did not support intraluminal androgen concentrations in the seminiferous tubules equivalent to controls; rete testis androgen concentrations were similar to controls, however. Pregnenolone administration at 2 mg X rat-1 X day-1 for 14 days did not maintain spermatogenesis nor intraluminal T concentrations in the seminiferous tubules equivalent to controls; however, a low level of spermatogenesis continued when intraluminal and tissue androgen concentrations were maintained at 10-20% of controls by either the testosterone and pregnenolone treatments.

Androgens↗
PubMed1985

Restoration effects of exogenous luteinizing hormone on the testicular steroidogenesis and Leydig cell ultrastructure.

In the present study, we explored the restoration effects of exogenous LH on Leydig cell ultrastructure and testicular steroidogenesis in rats that were deprived of endogenous LH via treatment with testosterone-17 beta-estradiol-filled Silastic implants for 10 days. Exogenous LH was supplied continuously via Alzet miniosmotic pumps at the rate of 1 microgram/h for 3, 6, 12, and 24 h or 1, 2, 4, 8, and 12 days. Testes were then perfused in vitro with medium containing 1) LH, 2) 20 alpha-hydroxycholesterol, or 3) pregnenolone substrate, which allowed us to assess LH-stimulated testosterone secretion, cholesterol side-chain cleavage activity, or the conversion of pregnenolone to testosterone, respectively. Other testes were perfusion fixed via the testicular artery for morphometric measurement of Leydig cell number and volume per testis and the surface area of Leydig cell cytoplasmic smooth endoplasmic reticulum (SER), inner mitochondrial membrane, and outer mitochondrial membrane. The results verified that Leydig cell smooth endoplasmic reticulum and inner and outer mitochondrial membrane surface areas are drastically diminished (P less than 0.05 vs. intact controls) by LH withdrawal. Also, the results verified that exogenous LH administered in situ restores Leydig cell ultrastructure and capacity to biosynthesize testosterone. However, the recovery of Leydig cell structure and steroidogenic reactions occurred at strikingly different rates upon restoration of LH after 10 days of the treatment with testosterone-17 beta-estradiol implants. For example, the restoration of testicular capacity to synthesize progesterone in response to LH stimulation or 20 alpha-hydroxycholesterol substrate was completed within 24 h. In contrast, the restoration of Leydig cell SER and testicular capacity to synthesize testosterone from pregnenolone was completed only after 8 days of continuous LH treatment (P greater than 0.05 vs. intact controls). Thus, our results show that LH rapidly restores Leydig cell post-LH receptor steroidogenic events up to and including cholesterol side-chain cleavage activity. Interestingly, there is no temporal association between the recovery of cholesterol side-chain cleavage activity and the surface area of inner mitochondrial membrane surface area. In contrast, 8 days are required to coincidentally restore SER surface area and the capacity of Leydig cells to synthesize testosterone from pregnenolone. We conclude that different cellular mechanisms are involved in the LH-dependent restoration of inner mitochondrial cholesterol side-chain cleavage activity and SER-associated conversion of pregnenolone to testosterone.

Animals↗
PubMed1984

The development of human benign prostatic hyperplasia with age.

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.

Adolescent↗
PubMed1984

Testicular androgen and estrogen secretion and benign prostatic hyperplasia in the beagle.

The natural history of benign prostatic hyperplasia (BPH) in the dog is characterized by a slow progression through two phases. The early phase of the disease process is characterized by glandular hyperplasia and occurs as early as 2.5 yr of age. The late phase of the disease is characterized by cystic hyperplasia and occurs after 4 yr. The results of the present study are the first to compare Leydig cell structure and steroidogenic function in dogs with BPH with those in age-matched controls. It was discovered that glandular BPH can occur in young dogs (2.5 yr) in which Leydig cell mass and ultrastructure and maximally stimulated androgen secretion are indistinguishable from those in age-matched controls. These results support the concept that the early phase of BPH (glandular hyperplasia) is not related temporally to some defect in the Leydig cell. In contrast, the late phase of BPH (cystic hyperplasia) in beagles 6 yr of age is associated with diminished smooth endoplasmic reticulum in the Leydig cell and with diminished production of androgens by perfused testes in vitro. During the course of these studies, we discovered that the testes of young beagles with BPH, but not age-matched controls or old beagles with BPH, secrete an unidentified molecule (putative estrogen). This molecule was characterized partially in that it is extractable from testicular venous effluent with diethyl ether, elutes in a discrete fraction in several different high performance liquid chromatographic systems, reacts with an antibody that recognizes 17 beta-estradiol, estrone, and estriol, and competes with 17 beta-[3H]estradiol for the rat uterine estrogen receptor. Based on the elution volume from high performance liquid chromatography, the unknown molecule (putative estrogen) is not estriol, estradiol, or estrone.

Androgens↗
PubMed1984

On the androgen microenvironment of maturing spermatozoa.

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.

Androgen-Binding Protein↗
PubMed1984

Effects of luteinizing hormone withdrawal on Leydig cell smooth endoplasmic reticulum and steroidogenic reactions which convert pregnenolone to testosterone.

Depletion of endogenous LH with sc implants of testosterone-17 beta-estradiol (T-E) caused a reduction in the Leydig cell smooth endoplasmic reticulum (SER) over a 10-day treatment period. Decreases also occurred in some, but not all, of the testicular steroidogenic reactions responsible for the conversion of pregnenolone (PREG) to testosterone. The conversions of progesterone (PROG) to 17 alpha-hydroxyprogesterone, 17 alpha-hydroxyprogesterone to androstenedione, and androstenedione to testosterone were significantly correlated (P less than 0.05) with the loss of Leydig cell SER. In contrast, the testicular conversion of PREG to PROG in rats deprived of endogenous LH for up to 10 days was identical to that in intact controls. Similar results were obtained when rats were hypophysectomized for 10 days. These results indicate that the Leydig cell enzyme activities responsible for converting PREG to PROG are distributed in the Leydig cell SER fraction which remains in Leydig cell cytoplasm 10 days after LH withdrawal, and thus, the bulk of these enzyme activities are sequested in a SER compartment that is resistant to LH withdrawal.

Animals↗
PubMed1983

Simultaneous measurement of four testicular delta 4-3-ketosteroids by isocratic high-performance liquid chromatography with on-line ultraviolet absorbance detection.

A method is described for the simultaneous measurement of testosterone, androstenedione, 17 alpha-hydroxyprogesterone and progesterone in venous effluent from in vitro perfused rat testes. The assay uses a non-radioisotopic internal standard (11 beta-hydroxyandrostenedione), isocratic high-performance liquid chromatography (HPLC) and UV absorbance detection at 240 nm. Either of two isocratic HPLC systems described in this report (tetrahydrofuran-methanol-water, 16:28:56; methanol-acetonitrile-water, 9:36:55; v/v/v) may be used, and assay specificity is the same in each. The separation and measurement of all four steroids are completed in 25 min. Sensitivity of the method is 10 ng for testosterone, androstenedione and 17 alpha-hydroxyprogesterone and 25 ng for progesterone. The linear range of the assay extends through 1600 ng which is the upper amount of each steroid tested. Average inter-assay coefficient of variation was 3.3% and average intra-assay coefficient of variation was 3.6%. This rapid, specific and reliable method requires minimal sample preparation and may be performed by inexperienced personnel.

Animals↗
PubMed1983

Testis function in rhesus monkeys treated with a contraceptive steroid formulation.

Rhesus monkeys (Macaca mulatta) were treated with testosterone (100 micrograms/kg/day) plus estradiol (0.5 micrograms/kg/day) via subcutaneous polydimethylsiloxane (PDS;Silastic) implants for thirteen months. This steroid regimen inhibited LH but not FSH secretion by the anterior pituitary, inhibited testicular testosterone and estradiol production and drastically reduced the numbers of vigorously motile spermatozoa in the ejacula. Importantly, these effects on testis function were achieved at dosages of testosterone and estradiol which approximate the amount of these two steroids produced daily in normal rhesus males.

Animals↗
PubMed1983

Somatic tissue responses of male rhesus monkeys treated with a contraceptive steroid formulation.

Rhesus monkeys (Macaca mulatta) were treated with testosterone (100 micrograms/kg/day) plus estradiol (0.5 micrograms/kg/day) via subcutaneous polydimethylsiloxane (PDS; Silastic) implants for thirteen months. This steroid regimen inhibited dramatically spermatogenesis. Gross and histopathological examination of the musculoskeletal, circulatory, endocrine (excluding the testis), central nervous, gastrointestinal and respiratory systems failed to uncover any untoward effects of the long-term exposure due to the contraceptive formulation. Similarly, no remarkable effects were observed in the ionic, chemical and formed elements of blood or secondary sex structures. Failure to detect secondary complications attributed to the steroid treatment offers further justification for evaluating a contraceptive strategy based on administering naturally occurring steroids at sustained rates approximating those at which they are produced endogenously in the human male.

Animals↗
PubMed1983

Contraceptive efficacy of testosterone-estradiol implants in male rhesus monkeys.

Rhesus monkeys (Macaca mulatta) were treated with testosterone (100 micrograms/kg/day) plus estradiol (0.5 micrograms/kg/day) via subcutaneous polydimethylsiloxane (PDS, Silastic) implants. This treatment caused a striking reversible sterility. No pregnancies were observed in females bred to the steroid-treated males. In contrast, there was no difference in pregnancy rate of females bred to control and steroid-treated monkeys for 14 weeks, beginning 17 weeks after removal of the steroid-filled implants.

Animals↗