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PubMed1983

Aromatization of testosterone to estrogen varies between strains of mice.

The nuclear uptake and retention of [3H]testosterone or one of its metabolites and the aromatization of testosterone to estrogen were examined in the Swiss--Webster mouse. Castrated male mice were injected with 0.2 micrograms of either [1 alpha, 2 alpha-3H(N)]testosterone or [1 beta, 2 beta-3H(N)]testosterone per 100 g of body weight and killed one and one-half hours later. The brains were removed and processed for autoradiography. A nuclear localization of testosterone or one of its metabolites was found in the nucleus (n) interstitialis striae terminalis, n. preopticus medialis, n. premamillaris ventralis and n. amygdaloideus medialis in animals injected with [1 alpha, 2 alpha-3H(N)]testosterone. In animals injected with [1 beta, 2 beta-3H(N)]testosterone a nuclear localization was found in only n. interstitialis striae terminalis, n. premamillaris ventralis and n. amygdaloideus medialis. The results suggest testosterone is aromatized to estrogen in n. preopticus medialis ventralis in the Swiss--Webster mouse. Together with previous data, these data suggest (1) the uptake and retention of testosterone or one of its androgenic metabolites and the aromatization of testosterone to estrogen varies between strains of mice and (2) there are two separate uptake and retention systems (receptors?) for testosterone and dihydrotestosterone in the brain in all animals studied thus far with autoradiographic techniques.

Animals↗

PubMed1983

Testosterone and photoperiod interact to regulate locomotor activity in male hamsters.

Testicular size, plasma testosterone levels, copulatory behavior, and daily locomotor activity are reduced in male hamsters after 10 weeks of exposure to short days. The role of testosterone in the short day-induced decline in locomotor activity was investigated, determining whether or not photoperiod could alter the effect of testosterone on activity. Castrated adult hamsters were allowed to acclimate to running wheels (wired to digital counters) and then were kept on either long (L:D 14:10) or short (L:D 6:18) days for 60 days. On Day 60, half of the animals on each light cycle were implanted with 12-mm-long testosterone-filled Silastic capsules; half received empty capsules. Digital counting of wheel-running activity continued for another 140 days. Blood samples taken on Day 200 confirmed L:D 14:10 and L:D 6:18 testosterone-treated hamsters had equivalent plasma testosterone levels. After an initial decline in activity, L:D 14:10 animals exhibited a progressive rise in mean running activity (from approximately 2000 to approximately 5000 wheel revolutions per day) through 100 days after the initiation of testosterone treatment. In contrast, activity levels in testosterone-treated L:D 6:18 animals remained uniform (approximately 2000 wheel revolutions per day) during this time, indicating exposure to short days rendered the hamsters less sensitive to the stimulatory effect of testosterone on activity. Of further interest was a marked increase in activity after 160-200 short days in animals treated with either testosterone-filled or empty capsules. It appears the total amount of daily locomotor activity in the hamster is modulated by circulating testosterone levels in a manner which is dependent upon the environmental photoperiod.

Animals↗

PubMed2005

Cardiovascular issues in hypogonadism and testosterone therapy.

A systematic literature search was conducted to investigate the cardiovascular issues related to hypogonadism and testosterone therapy. Vascular cells contain sex steroid hormone receptors. Testosterone can exert effects on the vascular wall, either by itself or through aromatization as estrogen. Hypogonadism is associated with central obesity; insulin resistance; low levels of high-density lipoprotein (HDL); high cholesterol levels; and high levels of low-density lipoprotein (LDL), triglycerides, fibrinogen, and plasminogen activator-1. Some observational studies show a correlation between low testosterone and cardiovascular disease (CVD), and others show no correlation. Interventional studies do not reveal a direct long-term relation between testosterone therapy and CVD. Short-term data suggest cardiovascular benefits of testosterone. Testosterone therapy has beneficial and deleterious effects on cardiovascular risk factors. It improves insulin sensitivity, central obesity, and lowers total cholesterol and LDL. In some studies, testosterone therapy has an HDL-lowering effect, and in other studies this effect is insignificant. This should not be assumed to be atherogenic because it might be related to reverse cholesterol transport and effects on the HDL(3) subfraction. The cardiovascular effects of testosterone therapy may be neutral to beneficial. There is no contraindication for testosterone therapy in men with CVD and diagnosed hypogonadism with or without erectile dysfunction. Caution should be exercised regarding occasional increases in hematocrit levels, especially in patients with congestive heart failure. Conversely, evidence does not support testosterone therapy in aging men for the purpose of cardiovascular benefit, despite claims to this effect. Further research on the cardiovascular benefits and risks of testosterone is strongly recommended.

Animals↗

PubMed2006

Testosterone directly induces progesterone production and interacts with physiological concentrations of LH to increase granulosa cell progesterone production in laying hens (Gallus domesticus).

Blocking testosterone action with immunization or with a specific antagonist blocks the preovulatory surge of progesterone and ovulation in laying hens. Thus, testosterone may stimulate progesterone production in a paracrine fashion within the ovary. To test this hypothesis, we evaluated the effects of testosterone and its interaction with LH on the production of progesterone by granulosa cells in culture. Hen granulosa cells obtained from preovulatory follicles were cultured in 96 well plates. The effects of testosterone (0-100ng/ml) and/or LH (0-100ng/ml) were evaluated. LH-stimulated progesterone production in a dose response manner up to 10ng/ml (p<0.01). Testosterone, up to 10ng/ml, increased progesterone production in a dose response manner in the absence of LH and at all doses of LH up to 1ng/ml (p<0.001). However, at supraphysiological concentrations of LH (10 and 100ng/ml) there was no further increase in progesterone production caused by testosterone (p>0.05). Finally, the addition of 2-hydroxyflutamide (0-1000mug/ml) to hen granulosa cells cultured with 10ng/ml of testosterone reduced progesterone production in a dose response manner (p<0.001). In conclusion, testosterone stimulates progesterone production in preovulatory follicle granulosa cells and interacts with physiological concentrations of LH to increase progesterone production. In addition, testosterone stimulation on granulosa cells is specific since the testosterone antagonist decreased testosterone stimulatory action.

Animals↗

PubMed2005

The current status of therapy for symptomatic late-onset hypogonadism with transdermal testosterone gel.

For over 50 years, testosterone therapy has been used for the treatment of hypogonadism. In recent years, there has been an increase in the use of testosterone therapy for men with late-onset hypogonadism, as more convenient and effective modes of application are developed. Testosterone therapy in these men can significantly improve their sense of well-being, and lead to increases in muscle and bone mass, upper body strength, virility and libido [Gruenewald, Matsumoto. J Am Geriatr Soc 2003;51:101; Morales. Aging Male 2004; in press]. However, ensuring that optimal testosterone therapy is achieved in men with hypogonadism remains challenging. Oral delivery of unmodified testosterone is not possible, due to rapid first-pass metabolism and its short half-life. Therefore, different derivatives and formulations of testosterone have been developed to enhance potency, prolong duration of action or improve bioavailability. In addition, several different routes of administration have now been evaluated, including intramuscular injections, oral formulations, transdermal patches, transbuccal systems and transdermal testosterone gel. Despite the broad range of testosterone therapy on offer, each form has its benefits and limitations, and some will suit one patient more than another. An important concern among clinicians is that testosterone therapy may cause or promote prostate cancer. While current evidence supports the safety of testosterone therapy, androgens are growth factors for pre-existing prostate cancer. Therefore, before therapy is initiated, careful digital rectal examination and determination of prostate-specific antigen (PSA) in serum should be performed, in order to exclude evident or suspected prostate cancer. The first 3-6 months after initiating testosterone therapy is the most critical time for monitoring effects on the prostate. Therefore, it is important to monitor PSA levels every 3 months for the first year of treatment; thereafter, regular monitoring (mostly for prostate safety but also for cardiovascular and haematological safety) during therapy is mandatory.

Administration, Cutaneous↗

PubMed2004

Circulating androgens enhance sensitivity to testosterone self-administration in male hamsters.

Young adult men are more likely to abuse steroids than individuals with low testosterone, including women, boys and older men. This suggests that circulating testosterone may enhance sensitivity to exogenous androgens. This hypothesis was tested using intracerebroventricular (i.c.v.) testosterone self-administration in orchidectomized males without testosterone (Orchx, n=8) and in orchidectomized males with chronic physiologic testosterone replacement (Orchx+T, n=8). Beginning 1 week after surgery, hamsters self-administered testosterone for 4 h/day in operant chambers at three doses (0.1, 1.0 and 2.0 microg/microl), each for 8 days. Afterwards, testosterone was replaced with vehicle for 8 days to test extinction. At 1.0 and 2.0 microg/microl, Orchx+T and Orchx males self-administered similar amounts of testosterone. However, at 0.1 microg/microl testosterone, only Orchx+T males showed a significant preference for the active nose-poke (Orchx+T active: 35.1+/-8.4 responses/4 h [mean+/-S.E.M.] vs. inactive: 16.5+/-1.7 responses/4 h, p<0.05; Orchx active: 16.7+/-4.9 responses/4 h vs. inactive: 13.5+/-3.1 responses/4 h, p>0.05). There was little change in operant behavior during extinction in Orchx+T males. However, when vehicle replaced testosterone, Orchx males extinguished their preference for the active nose-poke hole by day 6. These results support our hypothesis that circulating androgens enhance sensitivity to testosterone self-administration.

Anabolic Agents↗

PubMed2005

ICV testosterone induces Fos in male Syrian hamster brain.

Previous studies in our laboratory have demonstrated intracerebroventricular (ICV) self-administration of testosterone in hamsters. This suggests that androgens are reinforcing, independent of their anabolic effects. Furthermore, pharmacologic testosterone acts as a depressant: ICV testosterone infusion acutely reduces respiration, locomotion and body temperature. However, with chronic exposure, males develop tolerance. To understand mechanisms for androgen action, we looked for Fos expression after acute and chronic ICV infusion of testosterone or vehicle. 32 castrated males with chronic physiologic testosterone replacement (n=8/group) were infused ICV for 4h/day with 40 microg testosterone or 40 microl vehicle. Half of the males were perfused after the first day of ICV infusion; the remaining males were perfused after 15 days of ICV infusion. 60 microm coronal brain slices were cut. Every fourth section was stained for Fos. Additional sections were stained for androgen receptors (AR) and estrogen receptors (ER). Testosterone infusion induced Fos above control in the posteromedial bed nucleus of the stria terminalis (BSTPM), posteromedial amygdala (MeP), lateral habenula (LHb), median raphe (MnR), lateral pontine nucleus (Pn), and ventral tegmental area (VTA). In particular, Fos was elevated in the BSTPM, MeP, LHb, and VTA only after 1 day of testosterone. 15 days of testosterone enhanced Fos expression above control in the MnR and lateral Pn. Importantly, Fos was not present in all brain areas involved in reward or in those with dense steroid receptors. Furthermore, AR and ER immunostaining was unaltered by testosterone infusion. We conclude that pharmacologic testosterone activates select steroid-sensitive brain regions, as well as midbrain areas involved in reinforcement of commonly-abused drugs.

Analysis of Variance↗

PubMed2005

Testosterone, testes size, and mating success in birds: a comparative study.

Reproductive behaviors of vertebrates are often underpinned by temporal patterns of hormone secretion. We investigated interspecific patterns of circulating testosterone in male birds to test the hypothesis that testosterone plays a crucial role in sexual selection as determined by degree of polygyny and extra-pair paternity. We predicted that the evolution of increased levels of polygyny and extra-pair paternity would have resulted in the evolution of increased levels of testosterone to allow males more efficiently to compete for mates. This hypothesis was tested in comparative analyses of 116 species of birds using Generalized Least Squares Models. We assessed the importance of latitudinal distribution, because this can confound the relationship between testosterone and mating success. There were weak positive phylogenetic correlations between measures of testosterone and estimates of mating success at the social level, but this association appeared to be confounded by latitudinal distribution, a significant correlate of testosterone titers. However, we found a significantly positive relationship between peak and residual peak testosterone (which is the peak testosterone level that is controlled for the baseline level) and extra-pair paternity independent of latitude. These results suggest that selection pressures arising from social and sexual mating differently affected testosterone levels with the former being mediated by factors associated with latitudinal distribution. An analysis of residual testes size revealed a positive association between peak and residual testosterone and testes size relative to body size. In a path analysis, we show that relative testis size primarily evolved in association with intense sperm competition and thus high sperm production, and these mechanisms had a secondary impact on blood testosterone levels at a phylogenetic scale. Our results suggest that sperm competition has played an important role in the evolution of reproductive mechanisms in birds.

Analysis of Variance↗

PubMed1998

Effect of exogenous testosterone on prostate volume, serum and semen prostate specific antigen levels in healthy young men.

PURPOSE: We investigate and define the effects of exogenous testosterone on the normal prostate. MATERIALS AND METHODS: A total of 31 healthy volunteers 21 to 39 years old were randomized to receive either 100, 250 or 500 mg. testosterone via intramuscular injection once a week for 15 weeks. Baseline measurements of serum testosterone, free testosterone and prostate specific antigen (PSA) were taken at week 1. Semen samples were also collected for PSA content and prostate volumes were determined by transrectal ultrasound before testosterone injection. Blood was then drawn every other week before each testosterone injection for the 15 weeks, every other week thereafter until week 28 and again at week 40. After the first 15 weeks semen samples were again collected, and prostate volumes were determined by repeat transrectal ultrasound. RESULTS: Free and total serum testosterone levels increased significantly in the 250 and 500 mg. dose groups. No significant change occurred in the prostate volume or serum PSA levels at any dose of exogenous testosterone. Total semen PSA levels decreased following administration of testosterone but did not reach statistical significance. CONCLUSIONS: Despite significant elevations in serum total and free testosterone, healthy young men do not demonstrate increased serum or semen PSA levels, or increased prostate volume in response to exogenous testosterone injections.

Adult↗

PubMed2002

Cocaine-induced locomotor activity is enhanced by exogenous testosterone.

Anabolic-androgenic steroids are synthetic derivatives of testosterone, which are increasingly abused by adolescent populations who also abuse psychoactive substances. All these compounds lead to complex behavioral syndromes and the effects of their interactions remain unclear. The main aim of the present study was to determine the influence of testosterone on the locomotor activity-promoting effect of cocaine on male mice in an open field. In the three experiments, animals received two injections: firstly, testosterone or peanut oil, and secondly, cocaine or saline solution. In Experiments 1 and 2, testosterone (or oil) and cocaine (or saline) were injected 45 and 10 min, respectively, prior to activity recording. In the first experiment, we studied the effects of testosterone (2 mg/kg) on locomotor activity induced by different doses of cocaine (2, 4, 8, 10 or 12 mg/kg). In Experiment 2, we explored the effects of supraphysiological doses of testosterone (2, 6, 10 or 14 mg/kg) on animals treated with 10 mg/kg cocaine. Finally, in the third experiment, 14 mg/kg testosterone or vehicle was administered 15, 30, 45 or 75 min before activity data collection to animals that received 10 mg/kg cocaine or saline. Testosterone itself had no effects on spontaneous locomotor activity and, as was expected, cocaine increased locomotor activity dose-dependently. Given together, testosterone enhanced the cocaine-induced hyperactivity although not dose-dependently, the highest effects being found 45 min after testosterone injection. The present study confirmed the existence of an interaction between testosterone and cocaine at the central nervous system.

Animals↗

PubMed1999

Autoregulation of the androgen receptor at the translational level: testosterone induces accumulation of androgen receptor mRNA in the rat ventral prostate polyribosomes.

Several studies have documented that androgens have the ability to autoregulate their own receptor levels; however, the mechanism of such autoregulation remains poorly understood. Along these lines, our laboratory has shown that testosterone increased androgen receptor (AR) protein levels and binding in the castrated rat ventral prostate within 1 h. Ongoing protein synthesis was required for the testosterone effect, as the protein synthesis inhibitor cycloheximide blocked this effect. Testosterone and/or actinomycin D, an mRNA synthesis inhibitor, did not affect the steady-state AR mRNA levels. Therefore, we suggest that the early events induced by testosterone are posttranscriptional and that protein synthesis is required for the maintenance of AR protein and AR mRNA levels. In addition, we hypothesize that the testosterone posttranscriptional effect is primarily through the sequestering of AR mRNA in the prostate polyribosomes. To test this hypothesis, total RNA was isolated from prostate polyribosomes of controls and testosterone-treated rats and AR mRNA levels were quantitated by competitive reverse transcription-polymerase chain reaction. Polyribosomes profiles on linear sucrose gradients showed no difference in the sedimentation characteristics of ribosomal particles from the vehicle-treated control or testosterone-treated animals. Furthermore, because both polyribosomal preparations can direct protein synthesis to the same extent in a cell-free system, testosterone does not increase the efficiency of translation. However, competitive reverse transcription-polymerase chain reaction revealed that testosterone increases AR mRNA associated with polyribosomes by threefold after 1 h of treatment compared with control. These data suggest a rapid testosterone-mediated posttranscriptional mechanism, in which testosterone regulates the stability of the AR mRNA by sequestering it in polyribosomes, and consequently increasing its translation.

Animals↗

PubMed1999

Serum testosterone levels in African-American and white men undergoing prostate biopsy.

OBJECTIVES: Because androgen levels are known to influence prostate growth, we performed a prospective analysis of serum testosterone levels in all African-American and white men who underwent transrectal ultrasound-guided prostate biopsies to evaluate an abnormal digital rectal examination (DRE) and/or serum prostate-specific antigen (PSA) level greater than 4 ng/mL. METHODS: From June 1996 through July 1998, we evaluated 453 men (189 African-American and 264 white men) who underwent prostate needle biopsy because of an abnormal DRE or serum PSA greater than 4 ng/mL, or both. All men had morning serum testosterone levels determined just before undergoing prostate needle biopsy. Serum testosterone levels were compared on the basis of the prostate biopsy result (positive or negative for prostate cancer) and by race. RESULTS: A total of 453 men underwent prostate biopsy and had morning serum testosterone levels available for comparison. Of the 264 white men who underwent biopsy, 88 (33%) were found to have prostate cancer compared with 67 (35%) of 189 African-American men who underwent biopsy. In the white men without cancer, the mean serum testosterone level was 380. 19 ng/dL; those with prostate cancer had a mean serum testosterone level of 419.52 ng/dL. The mean serum testosterone level in African-American men without cancer was 424.30 ng/dL; it was 386.55 ng/dL in those with prostate cancer. There was no statistical difference in serum testosterone levels based on biopsy result or race. CONCLUSIONS: Although several studies have suggested that African-American men have higher serum testosterone levels than white men, these differences were noted only in men 40 years of age or younger. As was noted in our study, after age 40, African-American and white men have comparable serum testosterone levels. In addition, although prostate growth is androgen dependent, we found no difference in serum testosterone levels in men with and without prostate cancer.

Adult↗

PubMed1984

Testosterone and the decline of sexual behavior in aging male rats.

This experiment was designed to elucidate the role of testosterone in the decline of sexual behavior in aging males. Old (25 months) and middle-aged (10 months) male rats were given six tests (30-min long) of sexual behavior. The old males then were divided into two groups: intact and castrated with testosterone treatment. The middle-aged males were divided into three groups: intact, castrated with testosterone present all the time, and castrated with testosterone present only when tested. The old males were given another set of six tests 1 week after the operation (when 27.5 months old), and the middle-aged males were given three more sets of six tests 8, 26, and 39 weeks after the operation (when 15, 19, and 22.5 months old, respectively). Blood drawn after each test set was assayed for testosterone. The middle-aged intact males had higher levels of testosterone than the old intact males, and the testosterone-treated castrated males, whether middle-aged or old, had higher levels than the intact males. The presence of higher levels at the time of testing resulted in increased rates of mounting and intromitting in old males and an attenuated decline in the mount rate and percentage of tests with intromissions in middle-aged males. The middle-aged castrated males with continuous testosterone differed from the middle-aged castrated males with periodic testosterone only in the mount-intromission interval; the former group had a longer interval. It was concluded that testosterone, in general, does not prevent or reverse the decline in sexual performance of aging male rats and that the degree and rate of decline do not depend on whether or not testosterone is continuously present.

Aging↗

PubMed2001

Cerebrospinal fluid and plasma testosterone levels in post-traumatic stress disorder and tobacco dependence.

BACKGROUND: Little is known about the relationship between endogenous central nervous system (CNS) testosterone and any psychiatric syndrome. The goal of this study was to screen for potential abnormalities in CNS testosterone levels in patients with post-traumatic stress disorder (PTSD) and/or tobacco dependence. METHODS: We sampled cerebrospinal fluid (CSF) via a subarachnoid catheter over six hours and determined hourly basal CSF concentrations of testosterone in 11 combat veterans with PTSD and 12 normal volunteers. Smokers were abstinent for 11-17 h. Testosterone in CSF and matching plasma samples was assayed by radioimmunoassay. RESULTS: A factor analysis for effects of PTSD status, smoking status and sample time revealed significant effects of PTSD or smoking status, but not time, on CSF testosterone. CSF testosterone levels were lower in individuals with PTSD as compared with normal volunteers. When divided by smoking status, abstinent smokers had mean CSF testosterone levels higher than those of non-smokers. A similar analysis of plasma testosterone revealed no significant effects of any factor on plasma testosterone. CONCLUSIONS: These results indicate that CSF testosterone is significantly influenced by PTSD and smoking status. The exposure of the brain to altered levels of testosterone in smokers and patients with PTSD may have pathophysiologic significance in these conditions.

Adult↗

PubMed2001

A strong association between biologically active testosterone and leptin in non-obese men and women is lost with increasing (central) adiposity.

OBJECTIVE: In both humans and rodents, males have lower levels of leptin than females at any level of adiposity. Experimental data support the idea that testosterone exerts a negative influence on leptin levels. There are, however, major inconsistencies in available data concerning the possible association between androgenicity and leptin in humans. Reasons could be the influence of androgenicity on leptin production being dependent on body composition, and incomplete measures of biologically active testosterone levels. In the present study we have characterized the relationship between biologically active testosterone and leptin after careful stratification for gender and adiposity. DESIGN AND SUBJECTS: Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. MEASUREMENTS: Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Circulating levels of leptin, insulin, testosterone, androstenedione, sex hormone-binding globulin (SHBG) and insulin-like growth factor-1 (IGF-1) were measured by radioimmunoassays or microparticle enzyme immunoassays. Apparent concentrations of free testosterone and non-SHBG-bound testosterone were calculated. RESULTS: After adjustments for age, BMI and insulin, leptin levels were inversely correlated to testosterone levels in non-obese men (r=-0.56, P<0.01) and obese women (r=-0.48, P<0.05). In contrast, leptin and testosterone correlated in a positive manner in non-obese women (r=0.59, P<0.01). Levels of SHBG were negatively associated with leptin in men with low waist circumference (r=-0.59, P<0.01). The following factors were associated with leptin in a multivariate model: low levels of biologically active testosterone and SHBG in men with low and medium waist circumference, insulin in men with high waist circumference, high levels of testosterone and insulin in non-obese women, and BMI in obese women. CONCLUSION: We conclude that low leptin levels are associated with androgenicity in non-obese men and women and that the direction of this association is dependent on gender and body fat distribution. Based on these results we suggest that the relation between testosterone and leptin contributes to the gender difference in circulating leptin levels. International Journal of Obesity (2001) 25, 98-105

Adipose Tissue↗

PubMed1970

Studies on a testosterone glucuronyltransferase from the cytosol fraction of human liver.

An enzyme that conjugates the 17beta-hydroxyl group of testosterone was found in the cytosol fraction of human liver. The same enzyme preparation also conjugates the 16alpha-hydroxyl group of oestriol. The enzymic activity could not be sedimented by centrifuging the cytosol fraction at 158000g(av.) for 120min. The testosterone-conjugating as well as the oestriol-conjugating activities were found in the precipitate obtained after 30% saturation of the cytosol fraction with ammonium sulphate. Filtration of the precipitate through Sephadex G-200 enriched the testosterone-conjugating enzyme 50-fold and the oestriol-conjugating enzyme 100-fold. No separation of the two activities was achieved. With labelled testosterone the product of the reaction, testosterone 17beta-glucuronide, was identified by paper chromatography and by crystallization to constant specific radioactivity. Testosterone 17beta-glucuronyltransferase was active between pH7.0 and 8.6 in tris-HCl and tris-maleate buffers. The apparent K(m) values for testosterone and UDP-glucuronic acid were 6.4 and 25mum respectively. The enzyme was active between 37 and 45 degrees C; the activation energy was calculated to be 5kcal/mol. Oestriol did not influence the glucuronidation of testosterone. Controlled heating as well as alternate freezing and thawing of the purified enzyme preparation led to an inactivation of both testosterone-conjugating and oestriol-conjugating activities at similar rates. Testosterone and oestriol, when incubated together, gave a reaction rate that was approximately equal to the sum of the rates when the two substrates were incubated separately. The present findings suggest that testosterone and oestriol are conjugated by two separate enzymes.

Adolescent↗

PubMed1996

Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells.

We studied the in vitro effect of testosterone on spontaneous immunoglobulin production by human peripheral blood mononuclear cells (PBMC). Testosterone inhibited IgG and IgM production by PBMC both from males and females. The inhibitory effect of testosterone was revealed at doses more than 1 nM, increased dose-dependently, and reached a plateau at 100 nM. At doses < 1000 nM, testosterone did not reduce cell viability. Testosterone treatment reduced IgG production by 59.0% and that of IgM by 61.3% compared with control. Immunoglobulin production by B cells was also suppressed by testosterone, though the magnitude of the suppressive effect on B cells was lower than that on whole PBMC; testosterone-induced decrease of IgG production compared with control was 26.9% and that of IgM was 24.9%. Exogenous IL-6 partially restored the impaired immunoglobulin production of testosterone-treated PBMC; IgG production in testosterone culture was increased by IL-6 from 35.6% to 66.5% of control and that of IgM was also increased from 38.9% to 71.2%, respectively. Testosterone treatment reduced IL-6 production of monocytes by 78.4% compared with control, but neither affected that of T cells or B cells. These results suggest that testosterone may suppress immunoglobulin production of human PBMC directly by inhibiting B cell activity and indirectly by reducing IL-6 production of monocytes. It is thus indicated that this hormone may have protective and therapeutic effects on human autoimmune diseases.

Adult↗

PubMed1996

Serum levels of insulin-like growth factor I and insulin-like growth factor-binding protein 1 correlate with serum free testosterone and sex hormone binding globulin levels in healthy young and middle-aged men.

OBJECTIVE: Administration of testosterone has been reported to increase serum levels of IGF-I in men with isolated hypogonadotrophic hypogonadism. An inverse relation between serum IGF-I and sex hormone binding globulin (SHBG) is seen in GH deficient children. The biological action of IGF-I is thought to be influenced by binding proteins, one of which is insulin-like growth factor-binding protein-1 (IGFBP-1), which is not only a carrier protein but also actively regulates the cellular actions of IGF-I. These observations suggest associations between IGF-I, IGFBP-1, testosterone and SHBG in serum. The aim of the present study was to investigate these associations in normal healthy men. DESIGN AND PATIENTS: The associations between the serum levels of IGF-I and IGFBP-1 on one hand, and testosterone and SHBG on the other were investigated in 38 normal healthy young and middle-aged men. RESULTS: Serum levels of IGF-I decreased both with increasing age (r = -0.66, P < 0.001) and increasing SHBG levels (r = -0.46, P = 0.002), but increased with increasing free testosterone (f-testosterone) (r = 0.42, P = 0.005). These associations remained after mutual simultaneous adjustments in a multiple regression analysis. IGFBP-1 did not display any significant univariate correlation with age (r = -0.25, P = 0.06) or SHBG (r = 0.18, P = 0.14), but showed a significant positive correlation with both f-testosterone (r = 0.42, P = 0.004), and total testosterone (t-testosterone) (r = 0.39, P = 0.008). In a multiple regression analysis IGFBP-1 was positively correlated with both SHBG and f-testosterone, but not with t-testosterone. CONCLUSION: The present study suggests that among healthy young and middle-aged men, there is an association between serum levels of free-testosterone and SHBG on the one hand, and serum IGF-I and IGFBP-1 on the other.

Adult↗