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Does age-associated reduced Leydig cell testosterone production in Brown Norway rats result from under-stimulation by luteinizing hormone?

Previous studies have shown that reductions in Leydig cell testosterone production occur with aging in the Brown Norway rat. The recent observation that changes in luteinizing hormone (LH) pulse interval and amplitude also occur with aging suggests the possibility that age-related reduced Leydig cell steroidogenesis might be related to changes in LH. We reasoned that, if this is the case, exogenously administered LH should restore testosterone production by aged rat Leydig cells to the higher levels produced by Leydig cells of young rats. To test this hypothesis, young (4-month-old) and aged (21-month-old) rats received testosterone- and estradiol-containing Silastic implants designed to suppress LH and, thus, endogenous Leydig cell testosterone production. At the same time, the rats received miniosmotic pumps programmed to deliver pulsatile ovine LH at a predetermined daily dose. In some experiments, treatment effects were determined by measuring testosterone production by testes perfused in vitro with maximally stimulating ovine LH. In others, Leydig cells were isolated by centrifugal elutriation and Percoll density gradient centrifugation, and their in vitro ability to produce testosterone in response to maximally stimulating LH was determined. Testes or isolated Leydig cells from untreated young rats produced about twice as much testosterone as that produced by Leydig cells from aged rats. The administration of testosterone- and estradiol-filled implants for 5 days reduced testosterone production significantly at both ages. In young rats administered 24 microg LH/day for 5 days, along with the implants, testosterone production was maintained at the high level of the young controls. Comparable treatment of aged rats resulted in testosterone production only at the low level of the aged controls. Indeed, even with higher LH doses (36 microg/day), testosterone production by the aged rat Leydig cells did not rise above the aged-control level. The inability of exogenously administered LH to increase testosterone production by testes and Leydig cells of aged rats suggests that Leydig cell steroidogenic deficits in the aged Brown Norway rat are unlikely to be the result of age-related changes in LH.

Aging↗

PubMed2006

Endogenous testosterone levels, physical performance, and fall risk in older men.

BACKGROUND: Gonadal steroid levels decline with age in men. Whether low testosterone levels affect the development of common age-related disorders, including physical functioning and falling, is unclear. METHODS: This longitudinal, observational follow-up study sought to determine whether low testosterone levels are associated with physical performance and fall risk in older men. A total of 2587 community-based men aged 65 to 99 years were selected using a stratified random sampling scheme from a study cohort of 5995 volunteers. Bioavailable testosterone and estradiol levels and physical performance measures were determined from baseline. Incident falls were ascertained every 4 months during 4 years of follow-up. Generalized estimating equations were used to estimate risk ratios for the relation of sex steroids to falls. RESULTS: Fifty-six percent of the men reported at least 1 fall; many fell frequently. Lower bioavailable testosterone levels were associated with increased fall risk. Men with testosterone levels in the lowest quartile had a 40% higher fall risk than those in the highest quartile. The effect of low testosterone levels was most apparent in younger men (65-69 years) (relative risk, 1.8; 95% confidence interval, 1.2-2.7); testosterone level was not associated with falls in the oldest men (>/=80 years). Lower testosterone concentrations were associated with reduced physical performance. However, the association between low testosterone levels and fall risk persisted despite adjustment for performance. CONCLUSIONS: Falls were common among older men. Fall risk was higher in men with lower bioavailable testosterone levels. The effect of testosterone level was independent of poorer physical performance, suggesting that the effect of testosterone on fall risk may be mediated by other androgen actions.

Accidental Falls↗

PubMed2002

Refractory nonmotor symptoms in male patients with Parkinson disease due to testosterone deficiency: a common unrecognized comorbidity.

BACKGROUND: Many patients with Parkinson disease (PD) suffer from nonmotor symptoms including depression, anxiety, sexual dysfunction, decreased energy level, and an overall decline in quality of life. Comorbid depression, hypothyroidism, and sleep disorders may account for some, but not all, of these problems. Testosterone deficiency affects 20% to 25% of males over the age of 60 years in the general population and may cause signs and symptoms of the nonmotor symptoms seen in PD. We observed numerous patients with PD whose nonmotor symptoms were refractory to treatment. OBJECTIVE: To determine whether treatment of comorbid testosterone deficiency in male patients with PD can lead to improvements in refractory nonmotor symptoms. METHODS: Case studies were reviewed of the first 5 male patients who had PD with symptoms of testosterone deficiency who were treated in our clinic. All patients had low serum testosterone levels. Screening for testosterone deficiency symptoms using the St Louis Testosterone Deficiency Questionnaire was performed for 4 of the 5 patients. Additionally, to assess the prevalence of PD, total testosterone levels in 68 patients in our PD registry were sent for evaluation. RESULTS: Following testosterone replacement therapy, all 5 patients experienced significant improvements in their refractory nonmotor symptoms. Of 68 male patients with PD enrolled in our PD registry, 24 (35%) had plasma evidence of testosterone deficiency. We also noted that the risk of testosterone deficiency per decade was found to increase 2.8-fold per decade (P<.001), paralleling that which is found in the general elderly male population. CONCLUSIONS: The findings from this study reveal the heretofore unrecognized high prevalence of testosterone deficiency in elderly male patients with PD similar to that found in the general population. These symptoms, which may be refractory to antidepressants, anxiolytics, and antiparkinsonian medications, may respond to treatment with testosterone. More rigorous controlled studies will need to be undertaken to examine the treatment of this common comorbidity in male patients with PD.

Aged↗

PubMed1997

Schistosoma mansoni: susceptibility differences between male and female mice can be mediated by testosterone during early infection.

In murine Schistosoma mansoni infections, fewer adult worms develop in male than in female mice infected with the same number of cercariae. To evaluate a potential role for testosterone in this phenomenon, testosterone levels were manipulated in groups of CBA/J mice that were then infected and monitored for survival rates, worm burdens, organomegaly, and egg production. By 16 weeks of infection, more than 80% of mice in groups with low levels of testosterone (untreated females, castrated males, or carrier-treated castrates) were dead, while less than 40% of those in groups with high levels of testosterone (sham-castrated males, testosterone-treated castrates, or testosterone-treated female mice) succumbed to infection. The mean number of worms recovered from mice in the low testosterone level groups was comparable among groups, and significantly greater than that from those in high-testosterone-level groups. The degree of organomegaly observed correlated strongly with worm burden, but the number of hepatic eggs per female worm did not differ significantly between groups. When male mice were castrated or sham-castrated 5 weeks after S. mansoni infection, no significant differences in host survival occurred. Furthermore, female mice treated with testosterone demonstrated reduced worm burdens if the testosterone was given 10 days prior to infection but not if the testosterone was given 10 days or 5 weeks after infection. Thus, the host sex bias observed in parallel-infected male and female mice appears to be related to the presence of male gonadal tissue or testosterone early in infection, during the development of immature schistosomules.

Animals↗

PubMed1996

Effects of testosterone and 7 alpha-methyl-19-nortestosterone (MENT) on sexual and aggressive behaviors in two inbred strains of male mice.

Behavioral and endocrine effects of a synthetic androgen, 7 alpha-methyl-19-nortestosterone (MENT), which is not 5 alpha-reduced to dihydrotestosterone, were compared to those of testosterone in two inbred strains of male mice, C57BL/6J and DBA/2J, in two experiments. In the first experiment, seminal vesicle (SV) weights, kidney weights, and circulating steroid levels were examined in castrated mice treated with three doses of testosterone (3.125, 12.5, or 50 micrograms/day) or four doses of MENT (1, 4, 16, or 64 micrograms/day) for 2 weeks to determine the optimal replacement levels of the two androgens for behavioral studies. Both testosterone and MENT dose-dependently increased the SV weights that were greatly reduced, in both strains, by castration. MENT was more effective than testosterone in increasing SV weights, fully restoring them to intact levels in both strains, at the dose of 4 micrograms/day. At the dose of 12.5 micrograms/day, testosterone restored the SV weights completely in C57BL/6J and up to 80% in DBA/2J mice. DBA/2J mice were more sensitive than C57BL/6J mice to both androgens, as measured by kidney weights, although circulating levels of either steroid were very similar between the two strains of mice. In the second experiment, we investigated the effects of testosterone (12.5 micrograms/day) and MENT (4 micrograms/day) on sexual and aggressive behaviors. In each strain, MENT-treated and testosterone-treated mice showed similar numbers of mounts or intromissions. MENT was equally effective as testosterone to fully (C57BL/6J) or partially (DBA/2J) restore sexual behaviors as well as the SV weights to the intact levels. In contrast, MENT-treated mice of both strains were much less aggressive than testosterone-treated mice. In both C57BL/6J and DBA/2J mice, testosterone fully restored aggression to the intact levels as measured by aggression latency, number of aggressive bouts, and duration of aggression, whereas aggressive behaviors of the MENT-treated groups were not different from those of the castrated control groups. These results suggest that MENT can restore both male sexual behaviors and reproductive organ weights as effectively as testosterone, at one-third of the testosterone dose, without stimulating male aggressive behaviors.

Aggression↗

PubMed1997

Actions of testosterone in prepubertal and postpubertal male hamsters: dissociation of effects on reproductive behavior and brain androgen receptor immunoreactivity.

This study was conducted to determine whether there is a increase in responsiveness to the activating effects of testosterone on male reproductive behavior during puberty in male golden hamsters and whether responsiveness to behavioral actions of testosterone is correlated with the ability of testosterone to upregulate brain androgen receptor immunoreactivity (AR-ir). Sexually naive male hamsters were castrated at 21 or 42 days of age and implanted subcutaneously with a pellet containing 0, 2.5, or 5 mg of testosterone. One week later, males were given a 10-min mating test with a receptive female. Animals were euthanized 1 hr after the behavioral test, and blood samples and brains were collected. Plasma testosterone levels were equivalent in prepubertal and adult males that had been administered the same dose of testosterone. However, adult males exhibited more mounts, intromissions, and ejaculations than prepubertal males, demonstrating that postpubertal males are more responsive than prepubertal males to the effects of testosterone on sexual behavior. In both age groups, testosterone increased the number of AR-ir cells per unit area in several brain regions involved in male sexual behavior, including the medial preoptic nucleus (MPN), medial amygdala, posteromedial bed nucleus of the stria terminalis, and magnocellular preoptic nucleus (MPNmag). Surprisingly, testosterone increased AR-ir in the latter three regions to a greater extent in prepubertal males than in adults. Thus, prepubertal males are more responsive to the effects of testosterone on AR-ir in these regions. In a separate experiment, a pubertal increase in the number of AR-ir cells per unit area was found in both the MPN and MPNmag of intact male hamsters. These results indicate that a testosterone-dependent increase in brain AR during puberty may be necessary, but is not sufficient, to induce an increase in behavioral responsiveness to testosterone.

Animals↗

PubMed2004

Relationship between stress hormones and testosterone with prolonged endurance exercise.

Previous pharmacological and pathological studies have reported negative relationships between circulating testosterone and certain stress hormones (i.e., cortisol and prolactin) in humans. These relationships have subsequently been used in hypotheses explaining the subclinical resting testosterone levels often found in some endurance-trained males, but as of yet no one has specifically examined these relationships as they relate to exercise. Thus, we examined the relationship between total and free testosterone levels and cortisol, and between total and free testosterone and prolactin following prolonged endurance exercise in trained males. Twenty-two endurance-trained males volunteered to run at 100% of their ventilatory threshold (VT) on a treadmill until volitional fatigue. Blood samples were taken at pre-exercise baseline (B0); volitional fatigue (F0); 30 min (F30), 60 min (F60), and 90 min (F90) into recovery; and at 24 h post-baseline (P24 h). At F0 [mean running time = 84.8 (3.8) min], exercise induced significant changes (P<0.05) from B0 in total testosterone, cortisol and prolactin. All three of these hormones were still significantly elevated at F30; but at F60 only cortisol and prolactin were greater than their respective B0 values. Free testosterone displayed no significant changes from B0 at F0, F30, or the F60 time point. At F90, neither cortisol nor prolactin was significantly different from their B0 values, but total and free testosterone were reduced significantly from B0. Cortisol, total testosterone and free testosterone at P24 h were significantly lower than their respective B0 levels. Negative relationships existed between peak cortisol response (at time F30) versus total testosterone (at F90, r=-0.53, P<0.05; and at P24 h, r=-0.60, P<0.01). There were no significant relationships between prolactin and total or free testosterone. In conclusion, the present findings give credence to the hypothesis suggesting a linkage between the low resting testosterone found in endurance-trained runners and stress hormones, with respect to cortisol.

Adult↗

PubMed1976

Increased blood LH and testosterone after administration of prostaglandin F2alpha in bulls.

Two types of experiments were conducted to determine the relationship of changes in blood luteinizing hormone (LH) and testosterone in bulls given prostaglandin F2alpha (PGF2alpha). Episodic surges of LH and testosterone occurred in tandem, apparently at random intervals, on the average once during the 8-hr period after bulls were given saline. In contrast, after sc injection of 20 mg PGF2alpha, blood serum testosterone increased synchronously to a peak within 90 minutes four-fold greater than pre-injection values, and the testosterone surges were prolonged about three-fold compared to those in controls. Each of the PGF2alpha-induced surges of testosterone was preceded by a surge of blood serum LH which persisted for about 45 minutes and peaked at about 3 ng/ml. In a second experiment, PGF2alpha was infused (iv, 0.2 mg/min) for 20 hr; blood plasma testosterone increased from 7.0+/-0.6 to 16.0+/-1.5 ng/ml within 2.5 hr and remained near this peak for 10 hr. Then testosterone gradually declined to about 9 ng/ml at the conclusion of the 20-hr infusion. These changes in testosterone were paralleled by similar changes in blood plasma LH, although LH declined 3 hr earlier than testosterone. Random episodic peaks of blood plasma LH and testosterone typical of untreated bulls resumed within 8 hr after conclusion of PGF2alpha infusion. In both experiments, the surge of testosterone after PGF2alpha was preceded by increased blood LH. We conclude that increased LH after administration of PGF2alpha probably caused the increased testosterone. However the mechanisms of these actions of PGF2alpha remain to be determined.

Animals↗

PubMed2005

Testim 1% testosterone gel for the treatment of male hypogonadism.

OBJECTIVE: The aim of this work was to review the pharmacokinetic and clinical profile of Testim (Auxilium Pharmaceuticals, Norristown, Pennsylvania) 1% gel formulation of testosterone for the treatment of male hypogonadism. METHODS: An English-language search of the medical literature was conducted using PubMed (1998-December 2004) and EMBASE (1998-December 2004). Search terms included ag(e)ing male, male hypogonadism, late-onset hypogonadism, testosterone, testosterone deficiency, testosterone therapy, testosterone replacement therapy, androgen therapy, testosterone gel, and Testim. Bibliographies of retrieved articles were also reviewed. RESULTS: Five published clinical studies were reviewed. Testim 50 mg showed clear pharmacokinetic differences from AndroGel (known as Testogel in Europe; Unimed Pharmaceuticals, Inc., and Solvay Pharmaceuticals, Inc., Marietta, Georgia) 1% testosterone gel 50 mg, with increases of 30% (90% CI, 8%-57%) and 47% (90% CI, 20%-79%) versus AndroGel, respectively, in AUC(0-24h) for total serum testosterone and free testosterone. In a 30-day study of 638 men with hypogonadism, sexual desire scores and sexual motivation scores increased after Testim treatment at weeks 1, 2, 3, and 4 (each, P < 0.001). During 12 months of treatment with Testim 50 or 100 mg in 371 men with hypogonadism, total serum testosterone levels were raised to and maintained within the normal adult range, lean body mass increased by 2.2 kg (P < 0.001), fat mass fell by 2.1% (P < 0.001), and bone mineral density increased by 2.58% (P < 0.001). Mean scores for sexual desire, performance, motivation, and spontaneous erections were all significantly higher (all, P < 0.001) than at baseline for all time points during 12-month studies of Testim. In 2 studies comparing Testim with different testosterone patches, treatment with the gel resulted in 10-fold fewer application-site reactions than either patch. CONCLUSIONS: In men with hypogonadism, Testim gel raised and maintained serum testosterone levels to within the normal adult range, alleviated signs and symptoms associated with hypogonadism, and was well tolerated.

Administration, Cutaneous↗

PubMed2003

Interactions of testosterone and all-trans retinoic acid in regulation of androgen receptor expression in rat lacrimal gland.

All-trans retinoic acid down-regulates androgen receptor (AR) expression in lacrimal gland acinar cells in culture. The goal of this study was to determine if retinoic acid inhibits androgen-stimulated up-regulation of AR protein and AR mRNA expression in lacrimal glands of orchiectomized rats in vivo. Delivery of androgens to orchiectomized rats was accomplished by subcutaneous implantation of a 25 or 50 mg 21-day slow-release testosterone pellet. Rats were treated with retinoic acid by gastric gavage at 20 mg kg(-1) day(-1). After 7 days of treatment lacrimal glands were removed, AR protein expression in frozen sections was determined by immunohistochemistry and total RNA was probed for AR mRNA expression. Serum testosterone was measured by ELISA and serum retinoic acid was detected by HPLC. Orchiectomy decreases serum testosterone to 17 +/- 8 ng dl(-1), compared to 143 +/- 27 ng dl(-1) in normal rats, and reduces the number of lacrimal acinar cell nuclei expressing ARs to less than 30% of normal. Implantation of testosterone pellets restored lacrimal AR expression, but increased serum testosterone to more than 10 times the normal levels. Retinoic acid failed to inhibit AR expression in rats with high serum testosterone. Therefore a dose-response study was conducted in which testosterone was delivered by injection of a single dose of Depotestosterone at 2.5-200 mg kg(-1). Treatment of orchiectomized rats with a dose of testosterone as low as 2.5 mg kg(-1) resulted in serum testosterone levels of 62 +/- 17 ng dl(-1) and significantly increased lacrimal gland AR expression. Delivery of retinoic acid at 20 or 50 mg kg(-1) day(-1) simultaneously with a 2.5 mg kg(-1) testosterone injection prevented restoration of lacrimal gland AR expression and significantly reduced AR mRNA expression. A pharmacologic dose of retinoic acid inhibits AR expression in lacrimal gland acinar cells in vivo, as well as in vitro. This indicates that effects of retinoic acid and testosterone are antagonistic and suggests that retinoic acid may modulate effects of testosterone on the lacrimal gland.

Androgens↗

PubMed1998

Aromatase and testosterone receptor in the liver of the female green frog, Rana esculenta.

In the green frog, Rana esculenta, a peculiar feature of female reproductive endocrinology is an high level of circulating testosterone. Although several hypotheses have been set out to explain this phenomenon, the testosterone specific roles in female anuran have not been yet fully explored. This study results propose a testosterone implication in liver vitellogenin synthesis control, since in ovariectomized frogs the hormone induces an increase of circulating vitellogenin. The testosterone action could depend on its local conversion to 17beta-estradiol by aromatase which is present in frog liver tissue. Liver aromatase activity ranges from 7.5 to 26 fmoles E2 formed/mg protein/h and results higher as long as liver is engaged in vitellogenin synthesis. Aromatase activity seems depend on testosterone since it decreases after ovariectomy and is restored by testosterone injection in ovariectomized frogs. In green frog liver, testosterone binding molecules are present both in cytosol and nuclei. These molecule binding properties (Kd and Bmax in nM range; t 1/2 = 85 min; specificity) are in line with those of testosterone receptor of other lower vertebrate target tissue. In liver nuclei, testosterone receptor level undergoes modification throughout the sexual cycle which almost coincides with that of plasma testosterone level and liver aromatase activity. This could indicate that the testosterone induction of liver aromatase in frogs is via the testosterone receptor, as reported for aromatase of mammalian brain tissues.

Animals↗

PubMed1997

Effects of acute hyperinsulinemia on testosterone serum concentrations in adult obese and normal-weight men.

In a previous study performed in adult obese and normal-weight male subjects, we found that suppression of insulin levels by diazoxide reduced testosterone and increased sex hormone-binding globulin (SHBG) blood concentrations. These and other data suggested that insulin may have a regulatory capacity in testosterone secretion and/or metabolism in men, similar to what has already been demonstrated in women. In this study, we investigated the effects of acute hyperinsulinemia on major androgen levels, including testosterone, in two groups of normal-weight in = 11) and obese (n = 9) men. Acute hyperinsulinemia was obtained by the euglycemic-hyperinsulinemic clamp technique. Relationships between the degree of insulin resistance (ie, total glucose disposal [M value]) and testosterone levels were also evaluated. Basal testosterone levels in obese subjects (10.40 +/- 3.02 nmol/L) were significantly lower than in normal-weight controls (15.50 +/- 4.65 nmol/L, P < .01), whereas no difference was present in androstenedione and dehydroepiandrosterone sulfate (DHEA-S) concentrations. During the clamp study, testosterone was significantly increased in the obese group (11.79 +/- 3.64 nmol/L, P < .05) but not in the control group (15.81 +/- 4.54 nmol/L, P = NS). The other two androgens did not significantly change in either the obese or control group. There was a highly significant correlation between baseline testosterone concentrations, with M values suggesting a relationship between impaired peripheral insulin sensitivity and reduced plasma testosterone concentrations. It should be pointed out that there was a certain discrepancy in the testosterone variations, particularly in the control group, in which two thirds of the subjects had no change or some decrease in testosterone levels, whereas in the remainder testosterone increased over the values of the assay variation coefficient. These findings are consistent with the hypothesis that insulin may regulate testosterone blood levels also in male subjects. Whether these effects are primarily due to increased hormone secretion or reduced clearance needs to be investigated.

Acute Disease↗

PubMed2003

Effects of finasteride on serum testosterone and body mass index in men with benign prostatic hyperplasia.

OBJECTIVES: To examine the effect of finasteride on serum testosterone in men with benign prostatic hyperplasia (BPH). METHODS: The Proscar Long-Term Efficacy and Safety Study (PLESS) was a 4-year trial comparing the safety and efficacy of finasteride 5 mg with placebo in 3040 men with moderate to severe symptomatic BPH and enlarged prostates. PLESS included the prospective measurement of annual serum testosterone in a randomly selected subset of patients comprising approximately 10% of the randomized population (n = 301). RESULTS: Finasteride treatment led to a modest, but significant (P <0.001), increase relative to placebo in serum testosterone, with this increase greatest in patients who had low baseline testosterone levels. The larger testosterone increases seen in finasteride-treated patients in the lower baseline testosterone tertiles were associated with significant mean reductions relative to placebo at year 4 in body mass index (BMI), ranging from 0.6 to 0.8 kg/m2. No statistically significant between-group difference was found in BMI in the upper testosterone tertile. The sexual adverse experience profiles for finasteride and placebo were similar across the baseline testosterone cohorts examined. CONCLUSIONS: Finasteride treatment led to a generally modest increase relative to placebo in serum testosterone, with the greatest increases occurring in men with low baseline testosterone levels. The physiologic significance of these changes in men with low baseline testosterone levels is unclear, but the associated reduction in BMI is intriguing and may be related, because BMI is known to be negatively correlated with serum testosterone levels in men.

5-alpha Reductase Inhibitors↗

PubMed2004

Testosterone in tropical birds: effects of environmental and social factors.

Previous investigations suggest that male tropical birds have lower plasma testosterone concentrations than northern latitude species. To test whether this generalization is valid, we analyzed all currently available plasma testosterone data of tropical birds. We focused on peak breeding testosterone levels using phylogenetic and conventional statistics. Explanatory variables considered were social mating system, type of territoriality, breeding season length, and altitude. On average, tropical birds had lower mean peak testosterone levels than northern temperate birds. However, in several tropical species, testosterone levels were well within the range of northern latitude birds. Without controlling for phylogeny, breeding season length, type of territoriality, and altitude explained a significant proportion of the variance in testosterone levels. The shorter the breeding season, the higher the testosterone levels. Tropical birds that defend a breeding season territory had higher testosterone levels than birds that were year-round territorial or colonial, and testosterone levels were positively correlated with altitude. When controlling for phylogeny, only breeding season length predicted testosterone levels. In conclusion, we propose to refine previous notions of low plasma testosterone levels in tropical birds: short breeding seasons and perhaps environmental conditions at high altitudes precipitate conditions under which high testosterone levels are beneficial in the tropics.

Animals↗

PubMed2005

Separating behavioral and physiological mechanisms in testosterone-mediated trade-offs.

Testosterone often mediates trade-offs between reproduction and other life-history traits, which are usually investigated using testosterone implants. However, this approach does not distinguish between the physiological and behavioral effects of testosterone. We studied a wild game bird, the red grouse Lagopus lagopus scoticus, and took a new approach to investigate mechanisms linking elevated testosterone to increased parasite intensity. We caught males in autumn, removed their parasites, implanted them with the antiandrogen flutamide in combination with an aromatase inhibitor (FA males) or with empty implants (control males), and challenged them with parasites. The FA treatment increased testosterone concentration and physiological stress, but without enhancing testosterone-dependent behaviors, because testosterone receptors were blocked. FA males ended up with more parasites than the control males the following autumn, an effect similar to that of a testosterone treatment reported elsewhere. However, and unlike the testosterone treatment, the FA treatment did not affect home range, pairing, or breeding success. The results supported a physiological mechanism (increased susceptibility) linking elevated testosterone and increased parasite intensity. The FA treatment provided a new way of investigating testosterone-mediated trade-offs whereby testosterone concentration was increased while the effects on behavior were blocked, resulting in physiological costs without phenotypic benefits.

Albumins↗

PubMed1997

The effect of testosterone on androgen receptors and human penile growth.

PURPOSE: Recent rat studies suggest that early exposure to exogenous testosterone accelerates the loss of androgen receptors and compromises eventual penile length. In humans we hypothesize that down regulation of the androgen receptor is not the mechanism that stops penile growth. To test this hypothesis we investigated the effects of androgen deprivation and supplementation on the developing human penis. MATERIALS AND METHODS: A total of 15 normal human fetal penises at 7 to 19 weeks of gestation (mean plus or minus standard deviation 12 +/- 4.5) was divided in half sagittally. Specimens were grafted beneath the renal capsule of male athymic nude mice or nude rats. Three groups of host animals were prepared, including 10 with no testosterone that were castrated at grafting, 15 with testosterone and 5 with super testosterone in which 50 mg. testosterone propionate pellets were implanted subcutaneously at grafting. Each fetal penile specimen was its own control, since half was implanted into an intact animal and the other into a castrated or super testosterone host. Six weeks after grafting the specimens were analyzed for gross size (length), histology and expression of androgen receptors. RESULTS: All human fetal penile specimens grew from the nadir size and appeared as white exophytic growths on the surface of the host kidneys. Normal grafts were larger than castrate specimens (mean 6.9 +/- 2.1 versus 3.9 +/- 2.1 mm., p = 0.014). Mean length of the super testosterone specimens (7.3 +/- 2.3 mm.) was not significantly greater than that of normal specimens (p = 0.797). Histological analysis revealed that all specimens were composed of viable penile tissue. Cellular density of the castrate penises was approximately 2 times greater than that of the normal and super testosterone specimens (40.6 +/- 5.9 versus 25.1 +/- 2.8 cells per cm.2, p > 0.001), as calculated on enlarged micrographs. Supraphysiological doses of testosterone did not change the histology compared to controls. Immunohistochemical localization revealed androgen receptors expressed throughout the corporeal bodies, surrounding stroma and penile skin with intracellular localization to nucleus. The mean proportion of cells expressing androgen receptors was higher in the castrate (29.4 +/- 5.2 cells per cm.2) than in the normal (24.0 +/- 3.7) and super testosterone (24.7 +/- 4.5) grafts (p = 0.005). However, in regard to growth there was no change in the proportion of androgen receptor positive cells among the groups. CONCLUSIONS: Testosterone influences penile growth, possibly as a result of extracellular stromal expansion. The number of androgen receptor positive cells in the human fetal penis did not change among the castrate, normal and super testosterone hosts. These experiments support the hypothesis that penile growth cessation is mediated by mechanisms other than down regulation of the androgen receptor. Furthermore, these data support the hypothesis that early administration of androgen to prepubertal male individuals does not result in a shorter phallus in adulthood.

Humans↗

PubMed1985

Testosterone replacement in hypogonadal men: effects on obstructive sleep apnoea, respiratory drives, and sleep.

The obstructive sleep apnoea syndrome occurs predominantly in men. To determine the effect of testosterone on ventilatory function and whether testosterone may play a role in the development of obstructive apnoea, we performed waking ventilatory drive studies and sleep studies in five hypogonadal men. These androgen-deficient subjects were studied both while receiving no treatment and after six weeks of testosterone replacement therapy (testosterone oenanthate 200 mg i.m. every 2 weeks). Hypoxic ventilatory drive decreased significantly, from 158 +/- 39 (mean +/- SEM) off testosterone to 88 +/- 19 on testosterone therapy (P less than 0.05). Hypercapnoeic ventilatory drive did not change significantly on testosterone. Obstructive sleep apnoea developed in one man and markedly worsened in another man in association with testosterone administration. Both of these subjects also exhibited marked decreases in oxygen saturation with the development of cardiac dysrhythmias during sleep and large increases in haematocrit. The remaining three hypogonadal men did not demonstrate significant sleep apnoea either on or off testosterone. The percentage of sleep time spent in REM sleep increased from 14 +/- 3% to 22 +/- 2% when the men were receiving testosterone (P less than 0.01), but the episodes of sleep apnoea tended to occur during non-REM sleep. We conclude that in some hypogonadal men, replacement dosages of testosterone may affect ventilatory drives and induce or worsen obstructive sleep apnoea. The obstructive sleep apnoea syndrome is a potential complication of testosterone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2004

Serum adiponectin levels in hypogonadal males: influence of testosterone replacement therapy.

OBJECTIVE: Adiponectin is an adipocyte-specific secretory protein which exhibits antiatherogenic, anti-inflammatory and antidiabetic properties. We hypothesized that testosterone plays an important role in the regulation of its secretion in humans, as adiponectin concentrations are higher in women than in men and as testosterone administration is accompanied by a reduction in serum adiponectin in animals and by reduced protein secretion in cultured adipocytes. This study aimed to evaluate adiponectin levels in hypogonadal men prior to and during testosterone replacement therapy. SUBJECTS AND METHODS: In a retrospective study, adiponectin, total and free testosterone, oestradiol, SHBG, total cholesterol and triglyceride levels were evaluated in 31 hypogonadal men [HM; age, mean +/- SEM: 36.5 +/- 2.4 years; body mass index (BMI) 24.6 +/- 0.8 kg/m2] and 29 weight-matched eugonadal men (EM; age 30.8 +/- 1.5 years; BMI 23.4 +/- 0.6 kg/m2). In 13 HM (age 33.9 +/- 3.2 years; BMI 24.2 +/- 0.9 kg/m2) the same parameters were also evaluated after 6 months of testosterone replacement therapy. Correlation analysis between adiponectin and hormonal, biochemical and anthropometric parameters was performed in all subjects. RESULTS: Testosterone, free testosterone and oestradiol concentrations were significantly lower in HM than in EM (4.4 +/- 0.4 nmol/l, 78.4 +/- 10.9 pmol/l and 36.1 +/- 3.0 pmol/l, respectively, in HM vs. 21.9 +/- 0.7 nmol/l, 507.9 +/- 13.8 pmol/l and 65.2 +/- 1.8 pmol/l, respectively, in EM, P < 0.0001), while SHBG levels in HM were higher than in EM (54.4 +/- 7.5 vs. 30.9 +/- 2.2 nmol/l, P < 0.005). Serum adiponectin levels in HM were significantly higher than in EM (9.53 +/- 0.73 vs. 6.80 +/- 0.55 microg/ml, P < 0.01). Calculation of the Pearson coefficient showed that adiponectin levels in HM were not correlated with any of the anthropometric and hormonal parameters examined, but showed a significant negative correlation with serum triglycerides (r = -0.38, P < 0.05). Serum adiponectin levels were negatively correlated with body weight (r = -0.41, P < 0.05) in EM but not with other anthropometric, hormonal or biochemical parameters. Six months after initiation of testosterone replacement therapy, which increased testosterone and free testosterone levels to the normal range, adiponectin levels were significantly reduced in HM (6.37 +/- 0.93 vs. 9.26 +/- 1.01 microg/ml, P < 0.01) and similar to those recorded in EM. CONCLUSIONS: Compared to eugonadal subjects, hypogonadal men show higher adiponectin levels which are reduced by testosterone replacement therapy. This study indicates that testosterone exerts a regulatory role on adiponectin secretion in humans.

Adiponectin↗