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PubMed1979

[Total and free testosterone in the male depending on body weight (author's transl)].

Total testosterone, the fraction of unbound testosterone and free testosterone were measured in 116 males of varying body weight in the range of 80 to 256% of the ideal weight. There are 3 groups for the establishment of normal ranges of testosterone. Testosterone and the fraction of unbound testosterone were fairly constant in group I (80--160% of the ideal weight). In group II (160--200% of ideal weight) there was a tendency towards lower values. The relatively wide normal range for testosterone was not reached in only 5 of these 20 patients. In contrast, in group III (more than 200% of ideal weight) clear-cut changes of total testosterone were demonstable reaching only 38% (P less than 0.001) of control values. Changes were also clear for unbound testosterone which increased from 2.24 to 3.9% (P less than 0.001). The concentration of free testosterone decreased to a lesser extent (P less than 0.01). Despite the low total testosterone hypogaonadism was not demonstable clinically in the extremely obsese patients. According to these results "normal values" for total testosterone, the fraction of unbound testosterone and free testosterone could be established depending on body weight.

Adult↗

PubMed2007

Sex and testosterone effects on growth, immunity and melanin coloration of nestling Eurasian kestrels.

1. Sex differences in testosterone levels and sex-biased sensitivity to testosterone are the basis of some ideas postulated to account for sex-linked environmental vulnerability during early life. However, sex variation in circulating testosterone levels has been scarcely explored and never manipulated at post-natal stages of birds in the wild. 2. We measured and experimentally increased circulating testosterone levels in nestling Eurasian kestrels Falco tinnunculus. We investigated, possible sexual differences in testosterone levels and the effect of this hormone on growth (body mass and tarsus length) and cell-mediated immunity in males and females. We also explored testosterone effects on rump coloration, a highly variable melanin-based trait in male nestlings. We analysed data on circulating testosterone levels of nestlings in 15 additional bird species. 3. Increased levels of testosterone tended to negatively affect body condition, reduced cell-mediated immune responses in male and female nestlings and also diminished the expression of grey rump coloration in male nestlings. No sex differences were observed in testosterone levels in either control or increased testosterone group nestlings, and no interactions were found between sex and treatment. However, male nestlings showed a lower cell-mediated immune response than females in both groups. 4. Our results indicate first, that a high level of testosterone in all nestlings in a brood entails costs, at least in terms of immunity, coloration and probably growth. Secondly, sex differences in post-natal cell-mediated immunity, and consequently in the capacity to prevent diseases, cannot be explained by sex differences in circulating testosterone levels. Finally, by comparing published data at an interspecific level, contradictory sex patterns in circulating testosterone levels have been found, supporting the idea that circulating testosterone might not be a proximate factor causing sex-dependent vulnerability in bird species.

Aging↗

PubMed2004

Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease.

Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). Men with COPD have high prevalence of low testosterone levels, which may contribute to muscle weakness. We determined effects of testosterone supplementation (100 mg of testosterone enanthate injected weekly) with or without resistance training (45 minutes three times weekly) on body composition and muscle function in 47 men with COPD (mean FEV(1) = 40% predicted) and low testosterone levels (mean = 320 ng/dl). Subjects were randomized to 10 weeks of placebo injections + no training, testosterone injections + no training, placebo injections + resistance training, or testosterone injections + resistance training. Testosterone injections yielded a mean increase of 271 ng/dl in the nadir serum testosterone concentration (to the middle of the normal range for young men). The lean body mass (by dual-energy X-ray absorptiometry) increase averaged 2.3 kg with testosterone alone and 3.3 kg with combined testosterone and resistance training (p < 0.001). Increase in one-repetition maximum leg press strength averaged 17.2% with testosterone alone, 17.4% with resistance training alone, and 26.8% with testosterone + resistance training (p < 0.001). Interventions were well tolerated with no abnormalities in safety measures. Further studies are required to determine long-term benefits of adding testosterone supplementation and resistance training to rehabilitative programs for carefully screened men with COPD and low testosterone levels.

Aged↗

PubMed2002

Salivary testosterone levels in preadolescent children.

BACKGROUND: Saliva reflects the plasma free fraction of testosterone which is biologically active, and available for uptake by tissues. Testosterone concentration in saliva, though differing slightly from the concentration of unbound testosterone in serum, is in good correlation with the latter, indicating that salivary testosterone provides a reliable method for determination of serum free testosterone. The study aimed to investigate salivary testosterone levels and their changes in preadolescent children and to study sexual dimorphism. METHODS: Testosterone levels were determined in 203 healthy preadolescent children (77 girls and 126 boys) from saliva samples by radioimmunoassay. Sampling was performed once a year with respect to circadian and seasonal fluctuations of testosterone. Data were statistically analyzed by Statgraphic software. RESULTS: Mean salivary testosterone concentrations (+/- SD) were 0.038 +/- 0.012 nmol/L and 0.046 +/- 0.026 nmol/L for girls and boys, with the medians 0.035 nmol/L and 0.041 nmol/L, respectively. Statistical analysis did not prove changes in salivary testosterone concentrations in the preadolescent period of life, with an exception of the insignificant fall at the age of 7 years, and an insignificant rise at the age of 9 years in girls. CONCLUSIONS: Generally it can be concluded that salivary testosterone levels in our prepubertal subjects remained stable. There was no significant increase of salivary testosterone levels from the age of 6 until the age of 9 in both sexes. Sexual dimorphism in salivary testosterone levels was proved with significantly higher (p = 0.009) salivary testosterone levels in boys than in girls.

Child↗

PubMed2004

Effects of testosterone replacement in human immunodeficiency virus-infected women with weight loss.

The objective of this study was to determine whether physiological testosterone replacement increases fat-free mass (FFM) and muscle strength and contributes to weight maintenance in HIV-infected women with relative androgen deficiency and weight loss. Fifty-two HIV-infected, medically stable women, 18-50 yr of age, with more than 5% weight loss over 6 months and testosterone levels below 33 ng/dl were randomized into this double-blind, placebo-controlled trial of 24-wk duration. Subjects in the testosterone group applied testosterone patches twice weekly to achieve a nominal delivery of 300 mug testosterone over 24 h. Data were evaluable for 44 women. Serum average total and peak testosterone levels increased significantly in the testosterone group, but did not change in the placebo group. However, there were no significant changes in FFM (testosterone, 0.7 +/- 0.4 kg; placebo, 0.3 +/- 0.4 kg), fat mass (testosterone, 0.3 +/- 0.7 kg; placebo, 0.6 +/- 0.7 kg), or body weight (testosterone, 1.0 +/- 0.9 kg; placebo, 0.9 +/- 0.8 kg) between the two treatment groups. There were no significant changes in leg press strength, leg power, or muscle fatigability in either group. Changes in quality of life, sexual function, cognitive function, and Karnofsky performance scores did not differ significantly between the two groups. High-density lipoprotein cholesterol levels decreased significantly in the testosterone group. The patches were well tolerated. We conclude that physiological testosterone replacement was safe and effective in raising testosterone levels into the mid to high normal range, but did not significantly increase FFM, body weight, or muscle performance in HIV-infected women with low testosterone levels and mild weight loss. Additional studies are needed to fully explore the role of androgens in the regulation of body composition in women.

Adolescent↗

PubMed1985

Non-sex hormone-binding globulin-bound testosterone as a marker for hyperandrogenism.

Recent evidence suggests that the biologically active testosterone includes both the free and albumin-bound fractions, while the sex hormone-binding globulin (SHBG)-bound steroid dissociates less readily. To examine the significance of the non-SHBG-bound testosterone (i.e. free plus albumin bound) in hyperandrogenism, we obtained single blood samples from 17 normal women, 20 regularly menstruating but hirsute women, and 20 oligoamenorrheic hirsute women. Each serum sample was analyzed for total testosterone by RIA, SHBG-binding capacity was determined by protein precipitation with 50% saturated (NH4)2SO4, and albumin was measured by colorimetry. Non-SHBG-bound and free testosterone and the testosterone to SHBG molar ratio were then calculated. Non-SHBG-bound testosterone was also assayed using differential protein precipitation. There were significant differences among the groups in the mean values of all variables (all P less than 0.05) except albumin. Measurement and calculation of serum non-SHBG-bound testosterone produced similar results, suggesting that the binding equation is valid. There was considerable overlap between normal (control mean +/- 2 SD) and abnormal subjects in all variables except non-SHBG-bound testosterone, for which only 3 regularly menstruating and 2 oligoamenorrheic hirsute subjects were in the normal range. As total testosterone levels increased, there was a significant increase in the ratio of non-SHBG-bound testosterone to free testosterone. These data suggest that albumin becomes increasingly more important in testosterone binding as the total serum testosterone level increases and that non-SHBG-bound testosterone may be the optimal marker to identify hyperandrogenism in hirsute women.

Amenorrhea↗

PubMed1991

The assessment of bioavailable androgen levels from the serum free testosterone level.

Recently, it has been concluded that measurement of the serum free testosterone level is crucial for evaluating male gonadal function. However, the extent of the decline of serum free testosterone levels with aging and the actual levels in male infertility have not yet been clearly defined. In this study, the clinical significance of serum free testosterone levels was evaluated in a total of 248 subjects, including 120 healthy adult males (54 males aged 20-39, 26 males aged 40-59 and 41 males aged more than 60), 94 infertile males, 28 male hemodialysis patients, and 6 patients with Klinefelter's syndrome. Since the serum free testosterone levels correlate significantly with serum LH and FSH levels among 120 normal adult males, it appears that free testosterone has a biological action on the organ. In the subjects aged over 60, serum free testosterone levels were significantly decreased compared with the decrease of serum total testosterone. Thus, biologically active androgen levels decreased with aging. Serum free testosterone levels tended to decrease significantly from 40 years onwards. In infertile males, serum total testosterone levels were equal to those in normal adult males, but their serum free testosterone levels were significantly lower. This decrease of serum free testosterone may be one of the causes of their hypospermatogenesis. In male hemodialysis patients, serum total and free testosterone levels were not lower than in normal adult males. It is considered that the decline of percentage of serum free testosterone levels in aged males and infertile males was caused by increased serum sex hormone binding globulin (SHBG) levels. Several workers have shown that the production of SHBG is regulated by sex steroid hormones. In this study, however, serum SHBG levels were not correlated with the E2/T ratio. We concluded that measurement of the serum free testosterone level is of value in the endocrinological evaluation of male gonadal function.

Adult↗

PubMed2004

Pharmacokinetics and tolerability of a bioadhesive buccal testosterone tablet in hypogonadal men.

OBJECTIVE: A phase I single centre, open label study of the pharmacokinetics and tolerability of a buccal testosterone tablet (COL 1621) was carried out. DESIGN: Twelve testosterone-deficient males were treated with the buccal tablet twice daily for 7 consecutive days. Multiple blood samples were drawn for testosterone, dihydrotestosterone (DHT), bioavailable testosterone and sex hormone-binding globulin (SHBG). RESULTS: After COL 1621, means+/-S.D. serum testosterone level increased to a peak concentration of 26.6+/-5.8 nmol/l (7.7+/-1.7 ng/ml) at 4.8+/-5.8 h and stayed in the eugonadal range. Steady state was achieved within the first 24 h and was maintained in the normal range. The bioavailable testosterone, DHT and free testosterone index followed a pattern very similar to that of testosterone. The mean serum testosterone to DHT ratio was within the normal male range throughout treatment. There was only one treatment-related adverse event (headache). Two-thirds of patients indicated that treatment with COL 1621 was acceptable and that the tablet was convenient to use. Six patients (50.0%) preferred COL 1621 to their previous testosterone replacement therapy, two patients gave preference to their previous treatment and three patients found both treatments to be equally acceptable. Data for one patient was not available. CONCLUSION: We conclude that COL 1621 can efficiently elevate serum testosterone and DHT levels in hypogonadal men within the first day of application, achieve a steady state within 24 h and maintain serum testosterone in the normal range with a twice-daily treatment regimen. COL 1621 provides an effective alternative oral testosterone replacement therapy that gives physiological levels of testosterone and is well tolerated by the patients.

Administration, Buccal↗

PubMed2000

Long-term testosterone treatment prevents gonadal and adrenal tumorigenesis of mice transgenic for the mouse inhibin-alpha subunit promoter/simian virus 40 T-antigen fusion gene.

We have developed a transgenic (TG) mouse model for tumorigenesis of gonadal somatic cells using a 6 kb fragment of the mouse inhibin-alpha subunit promoter (Inh-alpha) fused with the simian virus 40 T-antigen (Tag) coding sequence. Gonadal tumors, of Leydig or granulosa cell origin, develop in the TG mice with 100% penetrance by the age of 5-8 months. Conspicuously, if the mice are gonadectomized, they develop adrenal tumors. Gonadal and adrenal tumorigenesis in these mice seem to be gonadotropin dependent. On the other hand, testosterone stimulates the proliferation of a cell line (C alpha 1) established from one of the adrenal tumors. The purpose of the present study was therefore to investigate further whether testosterone affects the growth of these gonadal and adrenal tumors in vivo. Two experimental models were used: (1) Tag TG/hypogonadotropic (hpg) double mutant mice and (2) castrated Tag TG mice. Both were treated between 1-2 and 7-8 months of age with Silastic rods (length 2 cm) containing testosterone. None of the control or testosterone-treated Tag/hpg mice developed gonadal or adrenal tumors. The castrated Tag TG mice displayed, upon microscopical examination, early stages of adrenal tumors, whereas those receiving testosterone did not show such changes. Testosterone increased the weights of gonads in the Tag/hpg mice, and those of uteri and seminal vesicles in both groups. In contrast, the adrenal weights were significantly reduced in both groups by testosterone treatment. Gonadal histology of the testosterone-treated mice showed hyperplasia of testicular Leydig cells and ovarian stroma. Spermatogenesis was induced by testosterone in the Tag/hpg mice. Adrenal histology of the testosterone-treated animals demonstrated the disappearance of the X-zone. Serum levels of FSH in testosterone-treated Tag/hpg mice were significantly increased, while those of serum LH were decreased. In conclusion, the present result indicate that the suppression of gonadotropins by testosterone implants in castrated Inh-alpha/Tag TG mice prevents the tumorigenesis of their adrenals. In intact Tag/hpg mice, testosterone implants were not able to induce gonadal or adrenal tumorigenesis. Although testosterone treatment was able to induce interstitial cell hyperplasia in gonads of the Inh-alpha/Tag mice, direct gonadotropin action is responsible for gonadal and adrenal tumorigenesis.

Adrenal Gland Neoplasms↗

PubMed2006

Use of a GnRH agonist and hCG to obtain an index of testosterone secretory capacity in the koala (Phascolarctos cinereus).

Testosterone secretion in mammals typically occurs in random pulses such that a single blood sample provides limited information on reproductive endocrine status. However, it has been shown in several species that an index of the prevailing testosterone biosynthetic capacity of the testes can be obtained by measuring the increase in circulating testosterone after injection of a GnRH agonist or human chorionic gonadotrophin (hCG). Hence, the aims of the present study were to examine fluctuations in testosterone secretion in the koala (n = 6) over a 24-hour period and then characterise testosterone secretion after injection of the GnRH agonist buserelin (4 micro g) or hCG (1000 IU). The latter was used to establish an index of the prevailing testosterone biosynthetic capacity of the koala testis. Individual koalas showed major changes in blood testosterone concentrations over 24 hours, but there was no apparent diurnal pattern of testosterone secretion (P > .05). Injection of buserelin and hCG resulted in an increase (P < .05) in blood testosterone concentration. After injection of exogenous hormone, near maximal concentrations of testosterone occurred at around 60 minutes. There was a tendency for plasma testosterone to decline after 90 minutes with buserelin, but concentrations remained close to the upper limit for 240 minutes with hCG. There were strong positive correlations between the average testosterone concentration over 24 hours and the maximum observed testosterone concentration after stimulation with GnRH and hCG (GnRH, r = .772; P = .07 and hCG, r = 1.0; P < .01). The findings in the present study confirmed that individual male koalas can show large fluctuations in blood testosterone concentrations over time and that a GnRH agonist and hCG can be used in the koala to obtain an index of the prevailing steroidogenic capacity of the testes.

Animals↗

PubMed2001

Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial.

BACKGROUND: Symptoms of male hypogonadism include low libido, fatigue, and dysphoria and are alleviated with testosterone replacement. The prevalence of major depressive disorder (MDD) in hypogonadal men is not known, nor is the antidepressant efficacy of testosterone replacement in depressed, hypogonadal men. METHOD: A 6-week double-blind, placebo-controlled clinical trial was conducted in 32 men with DSM-IV MDD and a low testosterone level, defined as total serum testosterone < or = 350 ng/dL. Patients were randomly assigned to receive weekly 1-mL intramuscular injections of either testosterone enanthate, 200 mg, or sesame seed oil (placebo). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression (HAM-D). RESULTS: Thirty patients were randomly assigned to an intervention; 13 received testosterone, and 17 received placebo. Mean +/- SD age was 52+/-10 years, mean testosterone level was 266.1+/-50.6 ng/dL, and mean baseline HAM-D score was 21+/-8. All patients who received testosterone achieved normalization of their testosterone levels. The HAM-D scores decreased in both testosterone and placebo groups, and there were no significant between-group differences: reduction in group mean HAM-D score from baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in those who received placebo. Response rate, defined as a 50% or greater reduction in HAM-D score, was 38.5% (5/13) for patients who received testosterone and 41.2% (7/17) for patients who received placebo. Patients receiving testosterone had a marginal but statistically significant improvement in sexual function (p = .02). CONCLUSION: In this clinical trial with depressed, hypogonadal men, antidepressant effects of testosterone replacement could not be differentiated from those of placebo.

Adult↗

PubMed1999

Regulation of thyroid hormones on the production of testosterone in rats.

The effects of a thyroidectomy and thyroxine (T4) replacement on the spontaneous and human chorionic gonadotropin (hCG)-stimulated secretion of testosterone and the production of adenosine 3',5'-cyclic monophosphate (cAMP) in rat testes were studied. Thyroidectomy decreased the basal levels of plasma luteinizing hormone (LH) and testosterone, which delayed the maximal response of testosterone to gonadotropin-releasing hormone (GnRH) and hCG in male rats. T4 replacement in thyroparathyroidectomized (Tx) rats restored the concentrations of plasma LH and testosterone to euthyroid levels. Thyroidectomy decreased the basal release of hypothalamic GnRH, pituitary LH, and testicular testosterone as well as the LH response to GnRH and testosterone response to hCG in vitro. T4 replacement in Tx rats restored the in vitro release of GnRH, GnRH-stimulated LH release as well as hCG-stimulated testosterone release. Administration of T4 in vitro restored the release of testosterone by rat testicular interstitial cells (TICs). The increase of testosterone release in response to forskolin and androstenedione was less in TICs from Tx rats than in that from sham Tx rats. Administration of nifedipine in vitro resulted in a decrease of testosterone release by TICs from sham Tx but not from Tx rats. The basal level of cAMP in TICs was decreased by thyroidectomy. The increased accumulation of cAMP in TICs following administration of forskolin was eliminated in Tx rats. T4 replacement in Tx restored the testosterone response to forskolin. But the testosterone response to androstenedione and the cAMP response to forskolin in TICs was not restored by T4 in Tx rats. These results suggest that the inhibitory effect of a thyroidectomy on the production of testosterone in rat TICs is in part due to: 1) the decreased basal secretion of pituitary LH and its response to GnRH; 2) the decreased response of TICs to gonadotropin; and 3) the diminished production of cAMP, influx of calcium, and activity of 17beta-HSD. T4 may enhance testosterone production by acting directly at the testicular interstitial cells of Tx rats.

Animals↗

PubMed1987

Induction of prostatic carcinomas and lower urinary tract neoplasms by combined treatment of intact and castrated rats with testosterone propionate and N-nitrosobis(2-oxopropyl)amine.

The effect of exogenous testosterone on prostatic carcinogenicity of N-nitrosobis(2-oxopropyl)amine (BOP) in intact and castrated rats was examined in Wistar-derived MRC rats. Daily administration of BOP (either s.c. or i.g.) for 3 days, at a dose of 20 mg/kg b.w. at the heights of prostatic cell proliferation induced by testosterone, led to development of a large number of prostatic tumors, the incidence of which, however, was dependent on the duration of testosterone administration. Testosterone given for life following BOP administration induced prostatic cancer in over 60% of rats, regardless of whether BOP was given orally or s.c., or whether the rats were orchiectomized or not, whereas tumor incidence was significantly lower in rats treated with testosterone for only a short period of time. One (3%) orchiectomized rat, which received testosterone only during BOP treatment, and four (15%) of rats treated with testosterone only for life also developed carcinomas. Histologically, a large number of BOP + testosterone-induced prostatic tumors were adenocarcinomas of various histological patterns and arose primarily from the dorsal lobe, whereas the great majority of squamous cell carcinomas were found in the ventral lobe. Simultaneously induced tumors were papillomas and carcinomas of the urinary bladder and urethra. Testosterone appeared to enhance the incidence of urinary bladder tumors, but not of the urethral tumors, whereas orchiectomy inhibited urethral carcinogenesis, and, to much lesser extent, urinary bladder tumor development. Rats treated weekly for 20 weeks with BOP (10 mg/kg/week i.g.) did not develop any prostatic tumors and all rats died of rectal cancer. Of rats treated similarly with BOP and with testosterone pellets for life following the last injection of BOP, 17% of rats developed prostatic cancer, all of the squamous cell type. Simultaneous testosterone and BOP treatment for 20 weeks followed by testosterone pellets for life resulted in a 39% tumor incidence (three adenocarcinomas, one anaplastic carcinoma, and five squamous cell carcinomas). The overall results suggest that testosterone plays an important role in the initiation of prostatic carcinogenesis, whereas the promotional phase is governed by the interaction of testosterone with other factors.

Animals↗

PubMedDate not supplied

Relationship between sleep-related erections and testosterone levels in men.

In order to identify a possible threshold for a serum testosterone level below which sleep-related erections are impaired and to compare this threshold with the normal laboratory range of testosterone serum levels, we studied 201 men, including hypogonadal and eugonadal subjects. The protocol included nocturnal penile tumescence and rigidity monitoring and the assay of basal testosterone, prolactin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) serum levels. The subjects were assigned to eight groups according to their testosterone serum levels. Group 1 had testosterone between 0 ng/dl and 99 ng/dl; the following seven groups had testosterone levels increased by 100 ng/dl per group. The groups of subjects with higher testosterone serum levels showed almost constantly higher values for the erectile parameters we studied than the subjects with serum testosterone < or = 99 ng/dl. On the contrary, subjects with higher testosterone serum levels showed higher values for only some erectile parameters compared to the subjects with serum testosterone between 100 and 199 ng/dl, without any significant difference among the groups with testosterone serum levels in the normal range. Our data suggest that the serum testosterone threshold for sleep-related erections is lower than the low end of the normal laboratory male range and is about 200 ng/dl. Further efforts are needed to find the precise serum testosterone ranges related to normal sleep-related erections and to normal sexual behavior, the testosterone ranges of which will probably not coincide.

Adult↗

PubMed1999

Pre- and postnatal testosterone administration induces proliferative epithelial lesions with neuroendocrine differentiation in the dorsal lobe of the rat prostate.

BACKGROUND: Androgens are implicated in the pathogenesis of prostatic carcinoma. We have elucidated the role of pre- and postnatal testosterone administration in the occurrence of proliferative lesions as well as neuroendocrine (NE) cells in the rat prostatic complex. METHODS: Female rats were given a single dose of 9 mg testosterone enantate i.m. on day 15 of pregnancy; it gave a high testosterone exposure to the fetus in the early organogenetic period of the rat prostatic complex. One group of the male offspring was followed without further testosterone treatment; a second group received testosterone only in the pubertal period; a third group was given testosterone from puberty and throughout life (46 weeks). These groups were compared to parallel groups (1A-1C) of male offspring without a testosterone supplement in pregnancy. RESULTS: The serum testosterone concentrations in the rats receiving testosterone were significantly higher than those of control rats. Histopathologically, the testosterone-induced proliferative lesions, mainly hyperplastic, were almost exclusively located in the dorsal lobe. Chromogranin A-immunoreactive (CgA-IR) cells were rarely found normally, but occurred more often in the proliferative lesions (P < 0.001). CONCLUSIONS: The incidence of proliferative lesions in rats exposed to testosterone only in puberty was comparable to the incidence found in those rats receiving testosterone in puberty and throughout life. This finding may have clinical implications for young athletes, who use testosterone as an anabolic drug. The occurrence of CgA-IR cells increased in proliferative lesions in the dorsal lobe of the rat prostatic complex.

Aging↗

PubMed2001

Biotransformation and disposition of testosterone in the eastern mud snail Ilyanassa obsoleta.

Elevated testosterone levels have been reported to be associated with imposex (pseudohermaphroditism), the superimposition of male characteristics such as a penis and vas deferens on female gonachoristic snails. Tributyltin (TBT), a marine biocide in anti-fouling paints, is a known causal agent of imposex. Evidence suggests that imposex is elicited by TBT-mediated changes in the biotransformation and disposition of testosterone. To identify potential targets of TBT in gastropod species susceptible to imposex, biotransformation and disposition of testosterone in normal individuals must first be characterized. Nonimposex mud snail, Ilyanassa obsoleta, readily extracted [(14)C]testosterone, added to aqueous media, and converted the testosterone to at least five apolar conjugates designated AP1 through AP5. All were retained by the organisms. No significant amount of [(14)C]testosterone was retained or eliminated as polar metabolites. Following enzymatic hydrolysis of the most abundant metabolite (AP1), free fatty acids and [(14)C]testosterone were liberated. Furthermore, AP1 was produced when homogenized snail tissue was incubated with [(14)C]testosterone and oleoyl coenzyme A or palmitoyl coenzyme A. These results indicate that AP1, which represents over 70% of the testosterone biotransformation products, is a fatty acid ester of testosterone. Apolar metabolites AP2-AP5 might represent testosterone derivatives that are multiply conjugated to fatty acid molecules. Fatty acid conjugates of testosterone have not been previously described in the gastropods. The esterification of testosterone to fatty acids might be a mechanism where by steroid titers are regulated and could represent a target of TBT toxicity.

Acyltransferases↗

PubMed2002

Testosterone rapidly reduces anxiety in male house mice (Mus musculus).

Eight experiments supported the hypotheses that reflexive testosterone release by male mice during sexual encounters reduces male anxiety (operationally defined in terms of behavior on an elevated plus-maze) and that this anxiolysis is mediated by the conversion of testosterone to neurosteroids that interact with GABA(A) receptors. In Experiment 1, a 10-min exposure to opposite-sex conspecifics significantly reduced both male and female anxiety 20 min later (as indexed by increased open-arm time on an elevated plus-maze) compared to control mice not receiving this exposure. In contrast, locomotor activity (as indexed by enclosed-arm entries on the elevated plus-maze) was not significantly affected. The remaining experiments examined only male behavior. In Experiment 2, exposure to female urine alone was anxiolytic while locomotor activity was not significantly affected. Thus, urinary pheromones of female mice likely initiated the events leading to the male anxiolysis. In phase 1 of Experiment 3, sc injections of 500 microg of testosterone significantly reduced anxiety 30 min later while locomotor activity was not significantly affected. Thus, testosterone elevations were associated with reduced male anxiety and the time course consistent with a nongenomic, or very rapid genomic, mechanism of testosterone action. In phase 2 of Experiment 3, the anxiolytic effect of testosterone was dose dependent with a 250 microg sc injection required. Thus, testosterone levels likely must be well above baseline levels (i.e., in the range induced by pulsatile release) in order to induce anxiolysis. In Experiment 4, a high dosage of 5alpha-dihydrotestosterone was more anxiolytic than a high dosage of estradiol benzoate, suggesting that testosterone action may require 5alpha-reduction. In Experiments 5 and 6, 3alpha,5alpha-reduced neurosteroid metabolites of testosterone (androsterone and 3alpha-androstandione) were both anxiolytic at a lower dosage (100 microg/sc injection) than testosterone, supporting the notion that testosterone is converted into neurosteroid metabolites for anxiolytic activity. Experiments 7 and 8 found that either picrotoxin or bicucculine, noncompetitive and competitive antagonists of the GABA(A) receptor, respectively, blocked the anxiolytic effects of testosterone. However, conclusions from these 2 experiments must be tempered by the reduction in locomotor activity that was also seen. The possible brain locations of testosterone action as well as the possible adaptive significance of this anxiolytic response are discussed.

Androstane-3,17-diol↗

PubMed1985

A theoretically sound and practicable equilibrium dialysis method for measuring percentage of free testosterone.

Free testosterone measured in serum equilibrated in vitro is considered a good index of biologically available testosterone even though a large part of free testosterone in vivo is derived locally from rapid dissociation of testosterone bound to albumin. The most accurate method for measuring free testosterone, however, is unsettled. The classical method--equilibrium dialysis--has been questioned because of the dilution of serum that it entails and the previous inability to achieve identical results with diluted and undiluted serum. Essentially identical measurements of free testosterone were achieved in diluted and undiluted charcoal-stripped serum by using the dialysis method and calculation reported here. The measured free testosterone in undiluted whole serum from women was only 4-6% lower than the estimated physiological values. These results were obtained using a validated calculation, controlling pH, using physiological bicarbonate buffer at 37 degrees C, maintaining a constant free ligand concentration for dilutions, measuring the water gain by the dialysis bag, and using highly purified labeled testosterone. The mean free testosterone for normal women was 0.17 ng/dl (0.11-0.23) and for hirsute women was 0.49 ng/dl (0.27-0.71). The testosterone not bound to testosterone-estradiol binding globulin, calculated from free testosterone and albumin concentrations, was close to the production rate/min of testosterone. The method should be adaptable to other ligands.

Dialysis↗