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Seminal androgen concentrations and residual sperm cytoplasm.

To explore a possible link between seminal androgen concentrations and residual sperm cytoplasm, which constitutes one of the cytological anomalies of the spermatozoon middle piece, testosterone (T), delta4-androstenedione, the precursor of T during testicular androgen biosynthesis and the active metabolite of T, dihydrotestosterone, were assayed in the seminal fluid of 37 patients. A statistically significant correlation was found by linear regression (r = +0.380, P = 0.020, y = 0.02x + 0.45) between seminal T concentrations and the percentage of spermatozoa with a residual cytoplasmic droplet. Given the impact on fertility of residual sperm cytoplasm, assessment of seminal T concentrations could provide useful information on the fertility status of patients.

Adult↗

Effect of prednisolone on serum and follicular fluid androgen concentrations in women with polycystic ovary syndrome undergoing in-vitro fertilization.

Increased androgen concentrations are thought to be detrimental to oocyte quality and reproductive potential. Adjuvant treatment with glucocorticoids has been tried to suppress androgens in women undergoing infertility treatment. In the present study 20 infertile women with polycystic ovary syndrome were prospectively randomized in a placebo-controlled study to receive either placebo or prednisolone 10 mg at night, during standard in-vitro fertilization (IVF) treatment. Serum samples for assays of gonadotrophins, steroids and sex hormone-binding globulin (SHBG) were collected before treatment, at down-regulation, and at oocyte retrieval. Up to five follicles in each ovary were analysed separately regarding follicular fluid and oocytes, the rest according to the clinic's routines. In the placebo group, serum dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulphate (DHEA-S) did not change between down-regulation and oocyte retrieval, whereas adjuvant prednisolone resulted in a significant decrease. In follicular fluid, adjuvant prednisolone resulted in significantly lower concentrations of DHEA-S as compared to placebo, no other significant differences were found. No significant differences were found in embryo characteristics or pregnancy rates between the groups.

Adult↗

Androgen-concentrating cells in the periventricular brain of the female rhesus monkey.

Although androgens act on the primate central nervous system to modulate both endocrine functions and a number of limbic-related behaviors, little is known about the anatomical location of the neurons which sequester these steroids in primates. To determine the prime location of these androgen-concentrating neurons in the forebrain of the primate, we injected three castrated female rhesus monkeys in the femoral vein with 1 microgram of 5 alpha-dihydro (1,2,4,5,6,7-3H) testosterone (3H-DHT, 107 Ci/mmole) per kg of body weight. One of these animals also received an IV injection of 100 micrograms/kg body weight of unlabeled dihydrotestosterone (DHT) to serve as a control. One hour after the injection of 3H-DHT we rapidly exsanguinated each animal. The forebrain was sliced and blocks containing the amygdala, diencephalon, frontal pole, and hippocampus were frozen and stored in liquid nitrogen until processing. The tissue was then processed for autoradiography. A specific topographic pattern of nuclear concentration of DHT or one of its metabolites was obtained in neurons of the basal hypothalamus, preoptic region, amygdala, and hippocampus. This pattern was similar to that found in rodent species.

Amygdala↗

Aromatase gene (CYP 19) polymorphisms and endogenous androgen concentrations in a multiracial/multiethnic, multisite study of women at midlife.

A limited number of studies have focused on androgens in women's health, particularly at the genetic level. We evaluated testosterone and estradiol (E2) levels among women in relation to 5 single nucleotide polymorphisms (SNPs) of the aromatase (CYP 19) gene, the cytochrome P450 enzyme that converts androgens to estrogens. We related 5 aromatase SNPs (CYP 19 rs2414096, CYP 19 rs936306, CYP 19 rs2446405, CYP 19 rs1008805, and CYP 19 rs749292) to serum androgen and E2 markers in 1,538 participants of the Study of Women's Health Across the Nation (SWAN), including 412 African American, 807 Caucasian, 151 Chinese, and 168 Japanese women. Aromatase allele and genotype frequencies differed significantly among racial/ethnic groups. Compared with other genotypes of the CYP 19 rs936306 polymorphism, the TT genotype was associated with a significant difference in the testosterone to E2 (T:E2) ratio--lower testosterone and higher E2 levels--especially in African American women. Japanese women with the AA genotype of the CYP 19 rs749292 polymorphism had lower testosterone and E2 levels but higher levels of sex hormone-binding globulin (SHBG) compared with Japanese women with the AG and GG genotypes. Among Caucasian women, there was markedly lower SHBG levels among those with the AA genotype of the CYP 19 rs2414096 polymorphism compared with other genotypes, after adjusting for age and body mass index. Three of 5 aromatase gene SNPs were associated with variation in serum androgen concentrations among women, both within and between racial/ethnic groups. Aromatase genetic markers may be important in understanding the emerging associations reported between endogenous androgens and women's health status.

Adult↗

Estrogen and androgen concentrations are not lower in the umbilical cord serum of pre-eclamptic pregnancies.

Reductions in breast cancer risk observed in daughters of pre-eclamptic pregnancies are hypothesized to be mediated by lower in utero estrogen concentrations. Whereas maternal urinary estriol excretion is generally lower in pre-eclamptic women, results for maternal blood concentrations are equivocal, and little is known about estrogen concentrations in the cord of pre-eclamptic pregnancies. Unconjugated estrogen and androgen concentrations were measured in mixed umbilical cord sera from 86 pre-eclamptic and 86 uncomplicated, singleton pregnancies, matched on length of gestation, maternal age, parity, and type of delivery. Pre-eclamptic and uncomplicated pregnancies were similar in maternal age, prepregnancy weight, maternal height, type of delivery, use and type of anesthesia, and sex of offspring. Estriol, estradiol, estrone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, and testosterone concentrations measured in cord sera were not significantly different in pre-eclamptics compared with uncomplicated pregnancies. Estriol was 9% lower (P = 0.43), and all of the other hormones were actually higher in pre-eclamptics with testosterone and estradiol approaching statistical significance (P = 0.06 and P = 0.12, respectively). These data do not support the hypothesis that the lower breast cancer risk in daughters of pre-eclamptic pregnancies is explained by lower in utero estrogen exposure.

Adolescent↗

Androgen concentrations in testicular and peripheral blood in the male Japanese quail.

Two experiments were conducted in which the concentrations of testosterone and dihydrotestosterone (DHT), an active metabolite of testosterone, were studied in the general circulation and in the testicular effluent. In the first experiment, blood samples taken from adult male quail were analyzed by radioimmunoassay for androgen and DHT concentrations; from these data, testosterone concentrations were calculated. The average concentration of androgen was 4238 pg/ml plasma. The average ratio of DHT/testosterone was .75. In the second experiment, steroid concentrations were compared in blood samples taken from the testicular vein and from the general circulation. Androgen concentrations in the general circulation were 36% of that obtained for the testicular effluent. In addition, testosterone and DHT concentrations in the general circulation were 36 and 46%, respectively, as high as concentrations in the testicular vein. Comparison of the average ratios of testosterone/DHT in the general versus testicular plasma revealed a higher ratio in the general circulation (.73 vs. .51, respectively). These results provide additional evidence for testosterone as the major male steroid secreted by the gonads. In addition, the relative concentration of DHT in the quail, which is higher than documented for most species, was higher in the peripheral than in the testicular circulation. This may indicate peripheral metabolism of testosterone to its active metabolite, DHT, and could have implications as to the availability of DHT for its target tissues.

Androgens↗

Effects of metformin on insulin resistance, androgen concentration, ovulation and pregnancy rates in women with polycystic ovary syndrome following laparoscopic ovarian drilling.

AIM: To evaluate the effects of metformin on insulin resistance, androgen concentration, ovulation rates and pregnancy rates in infertile women with polycystic ovary syndrome (PCOS). METHODS: Forty-two infertile women with PCOS were selected in this randomized clinical study. Basal steroid and gonadotropin levels were measured, and oral glucose tolerance test (OGTT) was performed. The patients were randomly divided into group 1 (n = 21) and group 2 (n = 21). Group 1 patients were treated with laparoscopic ovarian drilling (LOD). Group 2 patients underwent laparoscopic ovarian drilling (LOD) and received 1700 mg per day of metformin for 6 months. LOD was performed in women with PCOS using a unipolar electrode. Serum progesterone (P) level > 5 ng/mL was considered as a confirmation of ovulation. Ovulation and pregnancy rates were determined after six cycles. RESULTS: Serum androgens and insulin response to OGTT decreased significantly after metformin therapy. Mean serum P levels and endometrial thickness were significantly higher in cycles treated with metformin plus LOD (34.6 +/- 25.4 ng/mL, 8.4 +/- 1.1 mm) than in those treated with LOD alone (26.2 +/- 24.7 ng/mL, 7.9 +/- 2.8 mm) (P < 0.05). The ovulation (56 of 65 cycles, 86.1% vs 29 of 65 cycles, 44.6%) and pregnancy rates (nine of 21 women, 47.6% vs four of 21 women, 19.1%) were significantly higher in group 2 than in group I. CONCLUSIONS: Metformin improves insulin resistance, reduces androgen levels and significantly increases the ovulation and pregnancy rates in infertile women, following LOD.

Adult↗

Relationship between antler development and plasma androgen concentrations in adult roe deer (Capreolus capreolus).

Four male deer (4-5 years old), living in normal park conditions, were captured every 2 weeks in the year to study annual variations in androgen levels and the relationship between testicular activity and the antler cycle. Data were also obtained from 77 wild adult males (greater than 3 years old) caught in the forest. Plasma androgen concentrations rose briefly in April and markedly in August; the high values in August corresponded with the breeding period. From the time of casting to maximum growth was about 60 days; mineralization of the antlers then lasted for 45 days only. The mineralization phase of antler growth corresponded to the reactivation of testicular function in late January (0.43 +/- 0.16 to 1.99 +/- 0.42 ng androgen/ml, N = 4).

Androgens↗

Plasma androgen concentrations in diabetic women.

Plasma androgen levels were determined in women assigned to the following groups: idiopathically hirsute, diabetic, both idiopathically hirsute and diabetic, and normal. The androgens examined were androstenedione (AD), dihydrotestosterone (DHT), testosterone (T), and dehydroepiandrosterone (DHEA). We find statistical differences between young (less than 38 years) and older (larger than or equal to 38 years) controls at confidence levels of p less than or equal to 0.01 for AD, DHT, and T and of p less than or equal to 0.05 for DHEA. The results indicate that peak circulating androgen levels occur prior to age 30-35 years for women. There are no significant differences between the young controls and young idiopathically hirsute subjects, but a statistical difference exists between older hirsute and older controls for all four androgens (p less than or equal to 0.05). When a comparison is made among the diabetic, hirsute diabetic, and older control groups (all groups larger than or equal to 38 years), the diabetic group is significantly higher than the control in plasma AD (p less than or equal to 0.01) and DHEA (p less than or equal to 0.05). These same two steroids are also higher in the diabetic group than in the hirsute diabetic group (p less than or equal to 0.05), while the latter differs from controls only in testosterone levels (p less than or equal to 0.05). DHT levels are similar for all three groups.

Adult↗

Effect of a new 5 alpha-reductase inhibitor on size, histologic characteristics, and androgen concentrations of the canine prostate.

Mature male beagles were used in studies designed to determine the effect of the steroidal 5 alpha-reductase inhibitor 17 beta-N,N-diethylcarbamoyl-4-aza-4-methyl-5 alpha-androstan-3-one (4-MA) on size, histology, and androgen concentration of the prostate. Subcutaneous administration of 3 or 15 mg/kg/day for 43 days caused a sharp decline in prostate volume. flattening of prostatic epithelial cells, vacuolization of the cytoplasm and pycnosis of the nuclei. Whereas serum testosterone levels remained normal in dogs injected with 3 mg/kg/day, they were lower in those that received 15 mg/kg/day. Concentration of both testosterone and 5 alpha-dihydrotestosterone were reduced in the prostates of dogs that had received either 3 or 15 mg/kg/day of 4-MA. The 15 mg/kg/day level also appeared to adversely affect spermatogenesis. In a 43-day study, 4-MA given orally once each day at levels of 0.1, 0.3, or 1 mg/kg failed to cause a significant decrease in prostate volume. However, daily divided oral doses totaling 1 or 3 mg/kg were given in a 42-day test and both treatment levels produced significant reductions in prostate size.

5-alpha Reductase Inhibitors↗

Androgen concentration by a sexually dimorphic population of tachykinin-immunoreactive neurons in the rat ventral premammillary nucleus.

Strong connections with sexually dimorphic nuclei suggest that the ventral premammillary nucleus (PMv) may be involved in the mediation of reproductive behavior. Steroid autoradiography and immunohistochemistry were used to show that: (1) there is a sex difference in the numbers of PMv neurons that contain tachykinin peptides, (ii) dihydrotestosterone concentrating cells are densely distribution in the PMv and about a quarter of these also contain immunoreactive tachykinin and, (iii) size of the immunoreactive tachykinin population does not respond to alterations in levels of gonadal steroids in adulthood. Thus the PMv appears to make a contribution to the regulation of sexual behavior through androgen-concentrating, tachykinin-containing pathways that are anatomically distinct from estrogen receptive circuitry.

Androgens↗

Infravesical obstruction in aromatase over expressing transgenic male mice with increased ratio of serum estrogen-to-androgen concentration.

PURPOSE: The potential role of estrogen in the development of infravesical obstruction is still unresolved. Aromatase over expressing transgenic mice provide a novel instrument for investigating the consequences of prolonged systemic or local increases in endogenous estrogen concentrations. Two aromatase over expressing transgenic mouse strains with different prostatic phenotypes (reduced and normal size, respectively) were compared in urodynamic studies with each other and with the wild-type strain. MATERIALS AND METHODS: The bladder and urethra were exposed in adult male wild-type or transgenic mice. High frequency oscillations of intraluminal bladder pressure and flow rate from the distal urethra were simultaneously recorded with the mice under anesthesia. RESULTS: No changes were observed in voiding in MMTV-arom+ mice. These mice are known to have only slightly elevated estradiol concentrations in serum, suggesting a localized increase in estrogen production. In AROM+ mice the aromatase gene was detected in several organs, including the testis and bladder. These mice are known to have markedly increased estrogen and decreased serum androgen concentrations, and reduced prostate size. Compared with wild-type mice AROM+ mice showed higher mean maximal bladder pressure plus or minus standard deviation (33.1 +/- 6.4 versus 25.6 +/- 4.8 mm. Hg, p = 0.046) and decreased mean maximal flow rate (3.1 +/- 1.6 versus 17.7 +/- 5.4 ml. per minute, p <0.0001), consistent with the presence of the infravesical obstruction. Morphologically the proximal rhabdosphincter in AROM+ mice showed atrophy (relative mean thickness 0.005 +/- 0.015 versus 0.013 +/- 0.002 mm., p <0.0001). CONCLUSIONS: Activation of the aromatase gene during an earlier developmental stage under the ubiquitin C promoter and highly elevated serum estrogen concentrations may explain the differences in voiding and prostate size in the AROM+ mouse strain.

Animals↗

Androgen concentration and partial characterization of 5alpha reductase in the epididymis of the rhesus monkey.

The 5alpha reductase activity ofthe monkey epididymis was studied. The enzyme was found in particulate subcellular fractions, its distribution closely resembling that of the microsomal marker enzyme NADPH: cytochrome c reductase, suggesting an association of 5alpha reductase with membranes of the endoplasmic reticulum. Maximal enzyme activity was found at pH 5.4 and at 32--37 C. The crude nuclear preparation had a Km: 0.315 x 10(-6)M and Vmax: 168 pmoles/mg protein/h. The microsomal enzyme had a Km: 0.243 x 10(-6)M and Vmax: 828 pmoles/mg protein/h. Neither enzyme preparation was affected by addition to the incubation media of dihydrotestosterone (DHT) or 5alpha-androstane-3alpha,17beta-diol. The endogenous androgen concentration in the epididymides of 2 different monkeys, in ng/g wet weight was: DHT 20.81 +/- 1.98; T: 9.0L +/- 2.83; diol: 3.03 +/- 0.41.

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

Sexual behavior and plasma androgen concentrations in the male eider duck (Somateria mollissima).

Eider ducks showed clear tidal and seasonal cycles of display when involved in pair-formation behaviour. Plasma androgen (testosterone and dihydrotestosterone) concentrations did not follow similar tidal cycles but there was a 4-fold increase of androgen in spring when rates of display increased 2-fold. There was no difference in androgen levels in blood samples taken from paired birds before and after coitus. Androgens therefore appear to be essential for the expression of sexual behaviour, but there is no apparent quantitative correlation between overt sexual activity and androgen concentrations.

Androgens↗

Growth, body composition, and plasma androgen concentration of male broiler chickens subjected to different regimens of photoperiod and light intensity.

Day-old male Hubbard broilers (960) were assigned to one of four treatments (two pens of 120 birds per treatment) to evaluate the effects of high (150 lx) versus low (5 lx) light intensity and constant 23 h light (L):1 h dark (D) versus increasing (6L:18D increasing 4 h/wk to 23L:1D) photoperiod in a 2 x 2 factorial arrangement of treatments. Birds were raised to 8 wk on a typical commercial four-diet program. Low-intensity birds were heavier than high-intensity birds from 2 to 8 wk (3.25% heavier at 8 wk). Birds raised under constant photoperiod were heavier than birds raised under increasing photoperiod from 2 to 5 wk and at 7 wk of age (1.71% heavier at 7 wk). High-intensity bird carcasses had lower percentage body fat, weight of fat, and higher percentage body protein at 8 wk compared with low-intensity bird carcasses (7.77, 10.76, and 1.77%, respectively). High-intensity birds had smaller abdominal fat pads (weight and percentage of body weight) at 8 wk compared with low-intensity birds (15.46 and 12.17%, respectively). Photoperiod did not affect body composition. Birds treated with increasing photoperiod had larger testes (weight and percentage of body weight) at 8 wk compared with birds under the constant photoperiod (29.36 and 30.51%, respectively). Birds treated under increasing photoperiod had higher plasma androgen concentrations at 7 wk compared with birds under constant photoperiod (testosterone, .270 versus .188 ng/mL; androstenedione, .632 versus .494 ng/mL).(ABSTRACT TRUNCATED AT 250 WORDS)

Androgens↗

[Effect of ethinyl estradiol-dienogest combination on serum androgen concentrations].

Antiandrogens or progestins with an antiandrogenic component usually have only a weak antigonadotropic activity. It is thus possible that the antiandrogenic effect on the cellular level is cancelled or at least reduced by an increased ovarian androgen production. The aim of the four submitted clinical studies of the progestin and antiandrogen dienogest alone (0.5-2 mg/day) or of a combined regimen of ethinylestradiol (0.03 mg) plus dienogest (2 mg) (EE/DNG) was to examine the influence on the serum androgen and SHBG concentrations as well as on the serum FSH, LH, progesterone and 17 beta-estradiol concentrations in young women. Like the progesterone derivatives, dienogest has a relatively low antigonadotropic activity. Inhibition of ovulation is mainly produced by peripheral mechanisms such as the reduction of preovulatory 17 beta-estradiol secretion. Dienogest alone has no significant effects on the serum SHBG and androgen concentrations. Unlike this, the combination of EE plus DNG markedly increases SHBG concentrations (to 2.1-3.7 fold the basal levels). The decrease in serum androgens with total testosterone (by 17 and 40%), free testosterone (by 48 and 54%) and dehydroepiandrosterone sulfate (by 51%) corresponds to the values shown in the literature for other oral contraceptives with modern progestins. EE/DNG does not affect the serum concentrations of 5 alpha-dihydrotestosterone (DHT), although the marker of the peripheral transformation from T to DHT, androstanediol glucuronide, is distinctly reduced (by 38%). In a double-blind comparison no differences are found between EE/DNG and a regimen combining 0.02 mg of ethinylestradiol and 0.150 mg of desogestrel. Solely the SHBG concentrations, with EE/DNG, as expected, are significantly higher. In a sequential regimen, dienogest, chlormadinone acetate and desogestrel (progestins without binding to SHBG) enhance the inhibitory effect of ethinylestradiol sulfonate on free testosterone, whereas norethindrone acetate and levonorgestrel (progestins with a strong binding to SHBG) reduce this effect of the estrogen significantly. These results exclude the possibility that the very distinct antiandrogenic effect of dienogest on a cellular level is neutralised or reduced by an increased systemic supply of androgen.

Adolescent↗

[Serum androgens concentrations in women with idiopathic premature ovarian failure].

In this paper we investigated androgen serum concentration in women with idiopathic premature ovarian failure (POF). The research was conducted in 30 patients with POF and results of analysis were compared to 15--women after surgical oophorectomy and to groups of women matched in radomization: postmenopausal women (35 subjects) and healthy fertile women (27 subjects). We established that subjects with POF showed about 50% lower concentration of free testosterone compared to women who had undergone natural menopause and to fertile controls. Androstendione concentration was similar in all researched groups and was significantly lower than in fertile controls. Both women with POF and postmenopausal subjects showed lower concentration of dehydroepiandrosterone-sulfate (DHEA-S) compared to fertile women. Analysis of the results allowed us to come to conclusion that POF women, like women after surgical oophorectomy, suffer from relative androgen deficiency.

Adult↗

Androgen concentrations in expressed prostatic secretions: no correlation with tissue levels.

In an attempt to determine whether the androgen profiles of the prostate fluid (EPS) mirror the concentrations in the prostate tissue, we have measured testosterone and dihydrotestosterone (DHT) in EPS and correlated their levels to the concentrations found in hyperplastic prostate tissue (BPH) obtained from the same 19 patients. Although androgen concentrations in EPS were very high (testosterone = 106.7 +/- 81.9 ng/g dry weight; DHT = 54.2 +/- 11.2 ng/g dry weight), they did not reflect the concentrations measured in BPH tissue (testosterone = 7.56 +/- 1.54 ng/g dry weight; DHT = 10.54 +/- 0.63 ng/g dry weight). Additionally the accumulation of tissular DHT usually associated with BPH was not mirrored in the EPS specimens which demonstrated a relatively higher concentration of testosterone when compared to DHT. In EPS, there was also a very strong correlation between testosterone and DHT concentrations (r = 0.89; P less than 0.01). We have also measured zinc concentrations in EPS and BPH tissue but were unable to detect any relationship between the two parameters. Significantly, however, EPS zinc concentrations showed a close correlation with EPS testosterone (r = 0.73; P less than 0.01) and DHT (r = 0.69; P less than 0.01) concentrations.

Body Fluids↗