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At least 19 recordsLinked to original sources
PubMed1977

Correlative study of the morphology and C19-steroid metabolism of benign and cancerous human prostatic tissue.

Perineal punch biopsy specimens of human prostate with benign hyperplasia (BPH), well- and poorly-differentiated adenocarcinoma and transitional-cell carcinoma were incubated with testosterone-1,2-3H and 5alpha-dihydrotestosterone-1,2-3H. Incubations were carried out using a single tissue-radiosubstrate ratio and time point. Resulting radiosteroid patterns were related to histologic and ultrastructural features of these tissues. Well differentiated neoplasms had ultrastructural characteristics closely resembling hyperplastic epithelia. Both in BPH and in well differentiated carcinomas the C19-steroids were mainly metabolized by the 17beta-hydroxysteroid pathway. In contrast, cells in poorly-differentiated adenocarcinoma and transitional-cell carcinoma lacked the cytoplasmic organelles responsible for secretion; formation of 5alpha-reduced 17beta-hydroxysteroids was decreased in these carcinomas, while conversion to 17-oxosteroid radiometabolites remained unchanged or was greatly increased. These results indicate that loss of prostatic differentiation is attended by a trend from reductive toward oxidative radiotestosterone metabolism. Even in NAPDH-supplemented preparations of the majority of poorly-differentiated tumors, there was diminished transformation to 5alpha-dihydrotestosterone, the key intracellular hormone in the expression of androgenic activity in the prostate. These findings may explain why poorly-differentiated prostatic neoplasms are frequently unresponsive to anti-androgenic therapy.

Androgens↗
PubMed1978

The effects of 5alpha-reduced androgens on maintenance and regeneration of prostate glands and seminal vesicles in castrated and hypophysectomized rats.

The effects of 5alpha-androstane-3alpha, 17beta-diol (3alpha-diol) and 5alpha-androstane-3beta, 17beta-diol (3beta-diol) were studied in rats hypophysectomized and treated daily for 30 days with the steroids, starting on the day of surgery (hypophysectomized, H) or 30 days following the removal of pituitary (hypophysectomized regressed, HR). The ability of 3beta-diol to maintain and restimulate the prostate glands and seminal vesicles of castrated (C) and castrated regressed (CR) rats, respectively, was also studied. This androgen (3beta-diol) was able to maintain as well as rejuvenate to some degree the sexual accessory glands of all treatment groups. The prostate glands and seminal vesicles in both castrated experimental groups showed increased stimulation with progressively higher dosages of 3beta-diol. At all dose levels, stimulation of seminal vesicles of CR rats was comparable to that of non-regressed castrates. The prostate glands, on the other hand, showed better maintenance in the higher dosage group. In H rats, the stimulation of sexual accessory glands by both androgens was not significantly different than normal controls. The seminal vesicles and prostate glands of HR rats treated with 3alpha-diol were well stimulated and comparable to those of H rats treated with 3alpha-diol. The seminal vesicles of HR rats treated with 3beta-diol were also well stimulated, though not to the extent as those with 3alpha-diol treatment. The prostate glands of the 3beta-diol treated HR rats were significantly smaller than those of the 3alpha-diol treatment group. However, these miniature glands were morphologically stimulated as evidenced by mitosis of parenchymal cells and accumulation of secretory products in the alveoli. This study clearly indicates that 3beta-diol is biologically active and the degree of stimulation varies with the animal preparation in which the androgens were tested.

Androstane-3,17-diol↗
PubMed1976

The effect of metabolites of testosterone on the development of fertilizing ability by spermatozoa in the epididymis of castrated hamsters.

The effects of testosterone, 17beta-hydroxy-5alpha-androstane-3-one (5alpha-dihydrotestosterone; 5alpha-DHT), 5alpha-androstane-3alpha, 17beta-diol (3alpha-androstanediol; 3alpha-diol) and 5alpha-androstane-3beta, 17beta-diol (3beta-androstanediol; 3beta-diol) on the development of fertilizing ability by spermatozoa in the epididymis were compared in castrated hamsters. The left corpus epididymidis was ligated for 14 days in intact and castrated animals to prevent the in-flow of spermatozoa into the cauda epididymidis and the ductuli efferentes were bilaterally ligated. The fertilization rate of spermatozoa in the left cauda epididymidis of control animals decreased to 71.1% after 14 days whereas that of spermatozoa in the unobstructed right cauda epididymis remained at the control level of 100%. After castration, 50 mug testosterone, 25 mug 5alpha-DHT and only 9 mug 3alpha-diol/day were the minimal doses that facilitated normal development of fertilizing ability but 75 mug testosterone, 37.5 mug 5alpha-DHT and 12.5 mug 3alpha-diol/day were required to maintain sperm survival at the control level. However, 3beta-diol was ineffective for both sperm maturation and survival.

Androgens↗
PubMed1992

Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia.

The effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One- to 2-year-old beagle dogs were castrated and administered 75 mg/week of androstanediol (A-diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP-4238, 0.1 mg/kg/day of TZP-4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A-diol plus E2. Treatment with 0.5 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP-4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/kg/day of TZP-4238 decreased 5 alpha-reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP-4238 and CMA were effective in inhibiting the growth of hormone-induced canine BPH, and TZP-4238 was at least 5 times more potent than CMA. TZP-4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen-AR complex. TZP-4238 decreased 5 alpha-reductase activity by prevention of the androgen action described above.

Androstane-3,17-diol↗
PubMed1976

The effects of testosterone, 5alpha-dihydrotestosterone, 3alpha-androstanediol, and 3beta-androstanediol on epithelial fine structure of the rabbit epididymis in organ culture.

The fine structure of the corpus epididymidis of the rabbit has been studied following organ culture. Various modifications of tissue preparation and culture conditions were examined to obtain good maintenance of cellular integrity as well as to preserve sperm fertilizing ability. After 5 to 7 days in culture in the absence of hormonal support, the epididymal epithelium showed signs indicative of cellular regression. Such changes included shrinkage of the cells, loss of the border of stereocilia, decrease in smooth endoplasmic reticulum, and an increase in autophagic vacuoles. The presence of androgens in culture media prevented cellular regression to varying degrees, depending on the hormone utilized. With regard to maintenance of cellular integrity, potency of the androgens tested was as follows: 5alpha-dihydrotestosterone greater than or equal to 3alpha-androstanediol greater than testosterone greater than 3beta-androstanediol. Addition of insulin to dihydrotestosterone-containing cultures resulted in no improvement in maintenance. Phagocytosis of spermatozoa by epithelial cells was observed in cultured tubules and the degree of spermiophagy was inversely proportional to successful maintenance of fine structural characteristics of epithelial cells. The morphological findings reported here correlate well with the fertilizing ability of spermatozoa from cultured epididymis as reported in an accompanying communication.

Androstane-3,17-diol↗
PubMed1976

The effects of testosterone, 5alpha-dihydrotestosterone, 3alpha-androstanediol, and 3beta-androstanediol on the maturation of rabbit epididymal spermatozoa in organ culture.

The fertilizing ability of spermatozoa from epididymal tubules maintained in organ cultures from 1 to 7 days was assessed after artificial insemination into receptive does. It was found that spermatozoa from the distal corpus which were already capable of fertilizing eggs prior to the cultures retain this ability for 1 day without addition of hormone and for 3-4 days when testosterone (0.5 mug/ml) or 5alpha-dihydrotestosterone (0.5 mug/ml) is added to the culture medium. Spermatozoa from the proximal corpus which were not capable of fertilizing eggs prior to the cultures remain so after 1 day in cultures without addition of hormone. Testosterone, 5alpha-dihydrotesterone, 3alpha-androstanediol, or 3beta-androstanediol was added to cultures of proximal corpus at a concentration of 0.5 mug/ml. Only with 5alpha-DHT is the mean percentage of fertilization significantly higher than the percentage obtained without addition of hormone. Insulin does not potentiate the effect of 5alpha-DHT on sperm fertilizing ability. Epithelial growth factor is ineffective. Spermatozoa from the caput epididymidis kept in cultures for 1 to 4 days remain infertile. The results are discussed in light of the morphological findings presented in the preceding communication and in relation to the physiological requirement for sperm maturation in the epididymis.

Androstane-3,17-diol↗
PubMed1979

Role of the pituitary gland in experimental hormonal induction and prevention of benign prostatic hyperplasia in the dog.

The antiandrogen, cyproterone acetate (CPA), prevents development of prostatic hyperplasia, induced in castrated dogs by a 6 month-treatment with 5 alpha-androstane-3 alpha, 17 beta-diol (A)alone or in combination with 17 beta-oestradiol (E2). The immunoperoxidase technique was used to study functional cell types in the pars distalis of the pituitary gland and to detect growth hormone (GH) and prolactin (PRL) target sites in the prostate gland. Homologous radioimmunoassays for estimation of serum canine GH and PRL concentrations were also performed. Treatment with the combinations A + E2 and A + E2 + CPA resulted in morphological indications of stimulated GH and PRL cells and depressed gonadotrophs. This correlates well with an increase in PRL-dependent staining in glandular epithelium and fibromuscular tissue of the prostate gland. However, basal serum PRL and GH levels were not significantly affected. Treatment with A and A + E2 stimulated, while additional treatment with CPA clearly suppressed adrenocorticotrophin/melanotrophin (ACTH/MSH) cells. These findings indicate that an endocrine imbalance in hypothalamic-pituitary-adrenal function may be involved in induction and prevention of prostatic hyperplasia in the dog.

Androstane-3,17-diol↗
PubMed1975

A systematic study of testosterone metabolism in benign prostatic hypertrophy (BPH): in vitro results.

An in vitro system for testing steroids which might be effective in treating benign prostatic hypertrophy (BPH) has been developed based upon the transformation of H-3-testosterone into the 5-alpha-reduction products dihydrotestosterone and 3-alpha-androstanediol. In scrutinizing the influence of the amount of BPH-tissue, time, and pH, 300 mg of tissue incubated for 2 h at the physiological pH of 7.4 were used in the standard experiment. -The H-3-testosterone concentration was varied from 0.17-100 times 10-8 M. Plotting the resulting 5-alpha-reduction products as a function of testosterone concentration a hyperbolic pattern of enzyme kinetics ensued. Performing a double reciprocal plot of 4 experiments with double determination of each value regression lines could be computed. Those two regression lines most different in their slopes were considered "normal" limits. The rate of H-3-testosterone metabolism could not be enhanced after the endogenous testosterone content within the prostate glands had been used up by means of a preincubation. Scrutinizing the effect of heparin, a weak non-specific enzyme inhibitor, no suppression of the appearance of 5-alpha-reduction products was found. Damaging the BPH-cells, however, by repetitive freezing and thawing lead to an almost complete inhibition of H-3-testosterone turnover.

Androstane-3,17-diol↗
PubMed1976

[Effects of longterm HCG administration on testicular function in hemodialysis patients (author's transl)].

Thirtheen male patients with chronic renal failure undergoing regular dialysis treatment (2 X 8-10 hours/week) were treated with gonadotropins (HCG, Primogonyl) primarily 2 X 2,000 IU/week and later 2,000 IU/week. Before HCG administration and during 4-months HCG-therapy testosterone, dihydrotestosterone, Androstandiol, LH and FSH levels were determined by RIA-methods in 7-14 days intervals. Before HCG-application plasma testosterone levels were low and did not increase in the course of regular dialysis treatment. Derivates from testosterone like dihydrotestosterone and Androstandiol were elevated in plasma, presumbably because of accumulation in renal failure. LH-levels were slightly elevated on the average. FSH-levels showed a high individual variation but also seemed to be elevated on the average. HCG stimulation by exogenous HCG administration for short time resulted in a insufficient rise of testosterone levels as compared to normals. During prolonged HCG administration plasma testosterone levels increased to normal but dropped immediatly after cessation of therapy or reduction to less than 2,000 IU HCG twice/week. Body weight, plasma proteins, haematocrite and fertility did not improve significantly. These results indicate that in chronic renal failure androgen synthesis by testicular tissue is seriously impaired and does not improve under usual dialysis treatment. Feedback regulation of testosterone levels by increase of LH levels seems not to be sufficient although pituitary response is found to be normal. This may be explained by elevated levels of testosterone derivates which exert negative feedback effects.

Adult↗
PubMed1976

[Development of the rudimentary prostates of Ellobius lutescens (Microtinae) in organ culture; effects of androgens (author's transl)].

The structure of the rudimentary prostates of Ellobius lutescens is maintained intact after 6 days of organotypic culture in the absence of male hormones. Comparison with controls even shows a noticeable increase in the size of the epithelial cells. Adding male hormones to the culture medium does not modify the morphology of adult prostates, while it induces a sharp stimulation of immature prostates. In accordance with our previous results, these experiments show that the prostates of Ellobius lutescens lose their sensivity to androgens after puberty.

Age Factors↗
PubMed1976

Testosterone metabolism in male rat epiphysis.

Using radioactive substrate, thin-layer chromatography and recrystallization methods as well as differential centrifugation, gel filtration and electrophoresis, testosterone metabolism was investigated in male rat epiphyseal growth plate. 5alpha-androstane 3alpha-17beta-diol was found to be a major metabolite in vitro; lesser amounts of androstenedione and androstanedione, and a very small amount of 5alpha-dihydrotestosterone were also identified. Radioactivity was recovered in epiphyseal subcellular fractions 30 minutes following in vivo administration of tritiated 5alpha-dihydrotestosterone; within 2 hours radioactivity had fallen to essentially background level in all fractions but the cytosol. A testosterone binding protein could not be identified within epiphyseal cytosol.

Androstane-3,17-diol↗
PubMedDate not supplied

Lack of correlation between sex hormone binding globulin, adrenal and peripheral androgens in precocious adrenarche.

Sex hormone binding globulin (SHBG) is a specific steroid-binding plasma glycoprotein regulated by several different factors. Sex steroids are currently considered to be the main physiological regulators of this protein. Testosterone (T) in adults seems to be the main hormone active in lowering SHBG. The role of dihydrotestosterone (DHT) in such regulation, particularly in the prepubertal age, is not well understood, and no data exist about the role of 3 alpha-androstanediol (3A alpha) and its glucuronide. In adulthood, in addition to T, 5-ene steroids seems to play a role in the regulation of SHBG plasma concentration. To assess the effect of adrenal and peripheral androgens in modulating SHBG levels in the prepubertal age, we studied subjects with precocious pubarche secondary to precocious adrenarche (PA). PA represents, in fact, a good model of study as it is characterized by an increased production and action of adrenal androgen in females under 8 yr of age and in males under 9. Sixty-five subjects (55 females and 10 males; chronologic age: 3.6 - 8.2 yr (6.9 +/- 1.3, SD); bone age: 3.6 - 11 yr (7.6 +/- 1.9); BMI 17.9 +/- 3 kg/m2) were studied. Fifteen age-matched normal children (BMI 15.2 +/- 0.8 kg/m2) were studied as controls. Androstenedione (A), dehydroepiandrosterone (DHA) and its sulphate (DHA-S), T, DHT, 3Ad and its glucuronide (3AG) and SHBG were evaluated in all subjects. In PA cases serum SHBG levels (50 +/- 27 nM) were significantly lower (p less than 0.05) with respect to normal prepubertal patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗