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Suppression of basal plasma cortisol and adrenal androgen concentrations, but not of ACTH and cortisol responses to hCRH by low-dose dexamethasone in rhesus monkeys.

Glucocorticoid treatment at replacement doses does not result in a suppression of ACTH and cortisol responses to corticotropin-releasing hormone (CRH), while basal plasma concentrations of cortisol and adrenal androgens are efficiently suppressed 34 h after starting treatment. This finding could be demonstrated in rhesus monkeys receiving a continuous infusion of dexamethasone (1 microgram/kg per h) for 48 h and confirms our observations in patients on alternate-day prednisone therapy and in patients with congenital adrenal hyperplasia on glucocorticoid replacement therapy. We conclude that the decrease of basal adrenal steroid secretion resulting from glucocorticoid replacement therapy represents an effect on hypothalamic rather than on pituitary function.

Adrenocorticotropic Hormone↗

Low circulating estradiol and adrenal androgens concentrations in men on glucocorticoids: a potential contributory factor in steroid-induced osteoporosis.

Reductions in circulating estradiol concentrations could be implicated in the pathogenesis of steroid-induced osteoporosis (SIOP) in men. We assessed serum estradiol and adrenal androgens (dehydroepiandrosterone sulfate [DHEAS] and androstenedione) in 77 men (group A: idiopathic osteoporosis [IOP], n = 38, aged [mean +/- SD] 57.7 +/- 12.1 years; group B: SIOP, n = 39, aged 55.3 +/- 13.1 years). We also studied the relationship between bone mineral density (BMD) and serum estradiol in the group of men with SIOP. In group B, we observed a higher prevalence of low serum testosterone concentrations (<9.0 nmol/L) (P =.0052), which was significantly correlated with steroid dosage (r = -0.42, P =.0089) and estradiol concentrations (r = 0.42, P =.012). There was a significant positive association between BMD at the lumbar spine and serum estradiol (P =.004) in the men with SIOP (group B). A high proportion of subjects had low serum estradiol concentrations (<48 pmol/L) in both groups (group A: 44.7 %, group B: 36 %). Serum adrenal androgens concentrations were also significantly suppressed in group B (serum androstenedione-group A: 4.99 +/- 1.8; Group B: 2.1 +/- 1.6 nmol/L; P =.0001). Serum DHEAS was undetectable in 59% of patients in group B versus 6% in group A (P =.001). Reductions in androstenedione also correlated with steroid dosage (r = -0.35, P =.01). In conclusion, the data show that adrenal androgens synthesis is markedly suppressed in men with SIOP. The clinical relevance of this finding remains to be determined. This study also shows a positive association between serum estradiol and BMD and a high prevalence of low serum estradiol in men with SIOP. Low serum estradiol may contribute to bone loss in men with SIOP.

Adult↗

Androgen concentration in blacks with benign and malignant prostatic disease.

We measured the concentrations of testosterone and its metabolites in serum and prostate glands of Nigerians, a low risk population for prostatic tumours, by means of radioimmunoassay after solvent and chromatographic extractions. Our results show that the values of serum testosterone in normal, elderly Nigerian men (447.0 +/- 112 ng./dl.) and those with benign prostatic hypertrophy (BPH) (430 +/- 112 ng./dl.) were similar (p greater than 0.05) and compare with values reported for Caucasians. In the Nigerian patients with advanced prostatic cancer, the serum testosterone concentrations (314 +/- 202 ng./dl.) were significantly lower (p less than 0.001) than those of Nigerians with normal prostate and BPH. This again is similar to reports in Caucasians with metastatic prostatic cancer. The serum concentrations of testosterone metabolites in our patients were the same in normal BPH and cancer subjects. The ratios of testosterone to its metabolites were similar in our normal and BPH subjects but lower in cancer patients. Also the testosterone concentrations in BPH glands of Nigerians (0.5 +/- 0.03 SEM ng./gm.) compared favourably with those reported from the western world. The testosterone concentrations in malignant prostate gland (7.9 +/- .06 SEM ng./gm.) were significantly higher than those in hypertrophic glands. This again agrees with the pattern in Caucasians. The DHT concentrations (4.9 +/- 0.3 SEM ng./gm.) were considerably higher in BPH than in cancerous glands (1.7 +/- 0.2 SEM ng./gm.). This pattern has been documented elsewhere. Because the concentrations and pattern of distribution of androgens in serum and prostate gland of our patients are comparable to published Caucasian and black American values, any difference in incidence rates of BPH and carcinoma of the prostate between whites, Afro-Americans and indigenous Africans may not be related to androgens.

Aged↗

Maternal serum oestrogen and androgen concentrations in preeclamptic and uncomplicated pregnancies.

BACKGROUND: Epidemiological studies show a substantially reduced risk of breast cancer in adult daughters of preeclamptic pregnancies, and modest risk reductions have been demonstrated for mothers also. Alterations in pregnancy hormone concentrations, particularly lower in utero exposure to oestrogen, are hypothesized to mediate this association. METHODS: Pregnancy hormone concentrations were measured in maternal sera collected at hospital admission for labour and delivery from 86 preeclamptic and 86 uncomplicated, singleton pregnancies matched on length of gestation, maternal age, parity, and type of delivery. RESULTS: Case and control pregnancies were similar in several maternal and pregnancy factors. Serum unconjugated oestradiol, oestrone, and oestriol concentrations were not lower in preeclamptic pregnancies in a matched analysis with adjustment for race and whether blood was collected before or after labour commenced. Serum unconjugated androstenedione (506.3 versus 316.0 ng/dl; P = 0.0007) and testosterone concentrations (214.5 versus 141.9 ng/dl; P = 0.004), however, were significantly higher in preeclamptic compared with control pregnancies, whereas dehydroepiandrosterone (DHEA) and DHEA sulphate did not differ. CONCLUSIONS: These data do not support the hypothesis that cancer risk in mothers and offspring of preeclamptic pregnancies is explained by exposure to lower maternal blood oestrogen concentrations, but raise the possibility that androgens play a role.

Adult↗

Androgen concentration in the blood and spermatogenic function of tom cats during the breeding season.

In order to better understand androgen secretion in the tom cat during the breeding season, observations of diurnal changes in peripheral blood testosterone (T) levels, were made and the relation between androgen levels (androstenedione (A), 5 alpha-dihydrotestosterone (DHT). T) in testicular and peripheral vein blood was borne. Histologic examinations of the testis were also performed to investigate spermatogenic function. The 9 tom cats used in these studies were 2-3 years old, weighed 3.5-4.0 kg, and were raised in a room under natural lighting. As a result, diurnal peripheral blood T levels in the tom cat fluctuated greatly according to each individual, but since no definite trend could be identified, secretion was determined to be episodic. Although fairly large differences in the 3 types of androgen were observed in testicular vein blood depending on the individual animal, levels on the left and right were almost equal. Moreover, a correlation was found between the testicular and peripheral vein blood concentrations of the 3 androgens (A: p less than 0.01; DHT: p less than 0.05; T: p less than 0.01). Therefore, secretion of testicular androgen can be inferred by measuring peripheral blood androgen levels. Testicular histological examination revealed active spermatogenesis in all of the cats, and no significant inter individual differences were detected in either seminiferous tubule diameters or any of the various germ cells.

Androstenedione↗

Androgen concentrations and their receptors in the periurethral region are higher than those of the subcapsular zone in benign prostatic hyperplasia (BPH).

Benign prostatic hyperplasia (BPH) is an androgen-dependent disease that initially develops in the inner prostate, where the highest concentrations of testosterone (T) and dihydrotestosterone (DHT) are found. In this study, we have evaluated the cytosolic androgen receptors (ARc), the nuclear androgen receptors (ARn), and the concentrations of T, DHT, and 3alpha-androstanediol (3alphaDiol) in BPH tissue to verify the existence of a possible correlation between androgens and their receptor concentrations. Prostatic samples, removed by suprapubic prostatectomy in 15 untreated patients, were sectioned in periurethral, intermediate, and subcapsular zones. Testosterone, DHT, and 3alphaDiol were evaluated by radioimmunoassay after extraction and purification on celite microcolumns, and ARc and ARn were evaluated by means of dextran-coated charcoal method. In total tissue, mean levels of DHT, T, and 3alphaDiol were 2,531+/-308, 260+/-36, and 403+/-35 pg/mg of DNA (mean+/-SE), respectively. Cytosolic androgen receptors, detectable in all cases, were 16+/-2.8 fmol/mg of protein (mean+/-SE), and ARn, detectable in 12 cases, were 108+/-15 fmol/mg of DNA (mean+/-SE). A linear correlation between DHT and 3alphaDiol, T and DHT, and 3alphaDiol and ARn was found. If the different regions are considered, the periurethral zone, site of the primitive BPH nodule, presents the highest levels of androgens and ARn with respect to the other regions. This relative hyperandrogenism may be responsible for the growth-promoting processes of this area, leading to urinary obstruction.

Aged↗

Persistent intraprostatic androgen concentrations after medical castration in healthy men.

CONTEXT: The impact of serum androgen manipulation on prostate tissue hormone levels in normal men is unknown. Studies of men with prostate cancer have suggested that prostatic androgens are preserved in the setting of castration. Tissue androgens might stimulate prostate growth, producing adverse clinical consequences. OBJECTIVE: The objective of the study was to determine the effect of serum androgen manipulation on intraprostatic androgens in normal men. DESIGN: Thirteen male volunteers ages 35-55 yr (prostate-specific antigen < 2.0 ng/ml; normal transrectal ultrasound) were randomly assigned to: 1) a long-acting GnRH-antagonist, acyline, every 2 wk; 2) acyline plus testosterone (T) gel (10 mg/d); or 3) placebo for 28 d. Serum hormones were assessed weekly. Prostate biopsies were obtained on d 28. Extracted androgens were measured by RIA, and immunohistochemistry for androgen-regulated proteins was performed. RESULTS: The mean decrease in serum T was 94%, whereas prostatic T and dihydrotestosterone levels were 70 and 80% lower, respectively, in subjects receiving acyline alone compared with controls (P < 0.05). Despite this decrease in prostate androgens, there were no detectable differences in prostate epithelial proliferation, apoptosis, prostate-specific antigen, and androgen receptor expression. CONCLUSION: In this small study of healthy subjects, despite a 94% decrease in serum T with medical castration, intraprostatic T and dihydrotestosterone levels remained 20-30% of control values, and prostate cell proliferation, apoptosis, and androgen-regulated protein expression were unaffected. Our data highlight the importance of assessing tissue hormone levels. The source of persistent prostate androgens associated with medical castration and their potential role in supporting prostate metabolism deserves further study.

Adult↗

Body mass and physical activity are important predictors of serum androgen concentrations in young healthy men.

The relative importance of body mass index (BMI), demographic, and life-style factors in predicting androgen and sex hormone-binding globulin (SHBG) concentrations of young healthy men has not been clearly established. We evaluated the role of age, BMI, height, habitual physical activity, education, smoking, coffee and alcohol intake as predictors of serum testosterone, dihydrotestosterone, dehydroepiandrosterone sulfate, androstenedione, and SHBG concentrations in 100 healthy men 18-22 years old. BMI was the only independent predictor of dihydrotestosterone and dehydroepiandrosterone sulfate, and both BMI and physical activity were independent predictors of serum testosterone concentrations, whereas other variables did not appear to play a role of comparable importance.

Adolescent↗

Androgen concentrations in prostate and serum of the male and female Praomys (Mastomys) natalensis.

The levels of androgens in the male prostate, seminal vesicles, and serum, as well as in the female prostate and serum, were measured in the rodent Praomys (Mastomys) natalensis. Measurements were made in different age groups of both males and females using a sensitive radioimmunoassay. The results showed that the values for serum testosterone were 10 times greater in the male than the female. The concentration of serum dihydrotestosterone in the male was approximately one-tenth of the concentration of testosterone. The recovery of dihydrotestosterone from the prostate in the female and seminal vesicle in the male was low and these values were not considered. The concentrations of testosterone and dihydrotestosterone in the male prostate were 8.3 +/- 0.5 and 20.0 +/- 2.4 ng per g of wet tissue, respectively. The concentration of testosterone in the female prostate, 7.1 +/- 0.5 ng per g of wet tissue, was similar to that in the male. These studies have shown that the female Mastomys has a prostate which exists in a low androgen environment; it is suggested that this could be used as an experimental model for studying hormonal effects on the prostate.

Androgens↗

Androgen concentrations in epithelial and stromal cell nuclei of human benign prostatic hypertrophic tissues.

Prostate tissues removed from patients with benign prostatic hypertrophy were separated into epithelial and stromal components and nuclei purified from these. The concentrations of testosterone, 5 alpha-dihydrotestosterone, 5 alpha-androstane-3 alpha,17 beta-diol, 4-androstene-3,17-dione, 5 alpha-androstanedione and androsterone in pooled preparations of the purified nuclei were determined by radioimmunoassays after the purification of solvent steroid extracts by Lipidex-5000 column chromatography. The most abundant androgen measured was 5 alpha-dihydrotestosterone and it was significantly (P less than 0.05) more concentrated in the stromal nuclei than in the epithelial nuclei. The mean concentration of androsterone was also significantly (P less than 0.05) greater in the stromal nuclei whereas that of testosterone was equal in the two nuclear types. The concentrations of 5 alpha-androstane-3 alpha,17 beta-diol, 4-androstene-3,17-dione and 5 alpha-androstanedione were below the sensitivity limits of the assays in the majority of cases, but the results indicated that when detectable the first two were more concentrated in the stromal than the epithelial nuclei. The results emphasize the importance of the prostatic stroma in androgen metabolism, and the relative concentrations of 5 alpha-dihydrotestosterone and testosterone indicated identical 5 alpha-reductase activities in the nuclei in comparison with respective whole cell epithelial and stromal preparations. 5 alpha-Dihydrotestosterone concentrations were clearly higher than the nuclear androgen receptor levels previously reported from this laboratory.

Androgens↗

[Seminal parameters and androgens concentration in seminal plasma].

Basing on data from the literature authors present possible relation between seminal plasma levels of testosterone and dihydrotestosterone and disturbances of spermatogenesis. Review of the literature shows that androgens present in the seminal fluid may influence final seminal parameters and sperm fertilizing capacity. Most findings indicate that DHT is the androgen most closely related to spermquality. Many studies confirm that DHT concentration in sperm is significantly lower in infertile men affected by azoospermia or oligozoospermia and also in men with varicoceles. Improvement of seminal parameters and increase of DHT seminal plasma level was observed after varicocelectomy. The data shows that DHT values in ejaculate were lower in men with varicoceles and DHT seminal plasma levels increased in men whose sperm parameters improved after varicocelectomy. Several authors suggest that the low concentration of DHT in sperm could be a marker of azoospermia of obstructive origin. Positive correlation between DHT level in seminal plasma and sperm motility was also observed. In most of research there was no correlation between testosterone concentration in seminal fluid and sperm motility. A few authors reported that there was no difference in testosterone level in normo-, oligo- and azoospermic men, but recent studies indicate that the concentrations of both testosterone and dihydrotestosterone are significantly lower in samples from patients with abnormal sperm characteristics than in men with normozoospermia. Some investigators have suggested that an appropriate ratio of free testosterone to free estradiol in semen may be crucial in the processes that lead to fertilization and that there is no correlation between sperm density and level of testosterone in seminal plasma. Authors of the article emphasize that measurement of androgen in seminal plasma and usefulness of these parameters in clinical practice are underestimated.

Androgens↗

Chicken GnRH-II and salmon GnRH effects on plasma and testicular androgen concentrations in the male frog, Rana esculenta, during the annual reproductive cycle.

In the frog, Rana esculenta, two molecular forms of GnRH, coeluting with chicken (c) GnRH-II and salmon (s) GnRH, have been detected using HPLC and radioimmunoassay. Mammalian (m) GnRH seems to be also present. In amphibians the role of cGnRH-II seems to be primarily the involvement in the regulation of neuroendocrine processes and, while the mGnRH has been postulated to act as a neurotransmitter and/or neuromodulator, the activity of sGnRH-like material has not been investigated. Therefore, we have treated the frogs with single or multiple injections of cGnRH-II or sGnRH (6 micrograms) or both peptides (6 micrograms of each) to detect differences in the response measured as testicular or plasma androgen (testosterone plus 5 alpha-dihydrotestosterone) concentration during the annual reproductive cycle. The basal profile of testicular and plasma androgen shows that the spring peak disappeared in control animals given multiple injections and kept in short-term captivity. We show in the treatment with cGnRH-II and/or sGnRH that the effects of the peptides depend on the season, the experimental design, and the tissue in which androgen levels were measured. In particular, both peptides strongly stimulate androgen production during the autumn-winter period, the time of the greater response to the GnRHs when basal levels of steroids are highest.

Analysis of Variance↗