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Intratesticular testosterone concentration following intratunical administration in the hypogonadal animal.

The serum and intratesticular testosterone concentration (ITC) after testosterone administration in the tunica vaginalis (TV) sac compared to parenteral administration was studied in 20 dogs that were rendered hypogonadal by gonadotropin-releasing hormone antagonist ('Nal-Glu' GnRH antagonist) in a daily dose of 80 micrograms for 15 days. The 20 dogs were divided into two equal groups. Twenty milligrams of testosterone propionate were administered in the TV cavity in the TV group and intramuscularly (IM) in the IM group. In addition four dogs acted as controls and another four as sham controls. Serum and ITC were determined in all the dogs 1, 2, and 15 days after testosterone administration. Biopsies from TV were taken 3 weeks after testosterone injection for histologic examination. Serum and ITC were significantly reduced (P < 0.01) 15 days after GnRH antagonist. They increased after intratunical testosterone administration to reach the pre-GnRH antagonist level (P > 0.05). After IM testosterone injection, the serum testosterone increased to the pre-GnRH antagonist level (P > 0.05), while the ITC did not. The TV did not show histopathologic abnormalities apart from submesothelial infiltration with inflammatory cells in one dog. In conclusion, TV testosterone administration delivers a major dose of testosterone to the testicle without exposing other tissues to high testosterone levels. The method is safe and may be used as an office treatment. It may be tried in the treatment of patients who are infertile due to a low ITC.

Animals↗

The effects of actinomycin D and puromycin on the induction of the cytosol enzymes involved in the androgen metabolism by testosterone in female rat liver.

Induction of the cytosol enzymes involved in the androgen metabolism in the female rat liver by testosterone was studied. The treatment by testosterone propionate increased the production of 5beta-androstane-3alpha,17beta-diol in the 105.000xg supernatant when 4-14C-testosterone was used as a substrate. The conversion of 4-14C-androstenedione to labelled testosterone was increased by the injection of testosterone propionate into female rats. Actinomycin D or puromycin which was administered for four days with daily subcutaneous injections of testosterone propionate prevented the increase of these enzymes by testosterone propionate. Actinomycin D given once with the final injection of testosterone propionate blocked the induction of cytosol 17beta-hydroxysteroid dehydrogenase by the treatment of testosterone propionate, whereas puromycin given in the same manner as actinomycin D had no such a blocking effect on the enzyme. Both of these antibiotics given once with the final injection of testosterone propionate showed no preventing effects on the induction of cytosol delta4-5beta-reductase by testosterone propionate.

Androgens↗

Photoperiod and testosterone independently affect vocal control region volumes in adolescent male songbirds.

Previously, we found that, unlike adults, adolescent male dark-eyed juncos (Junco hyemalis) maintained large Area X volumes despite having low plasma testosterone concentrations. Other studies indicate that photoperiod may act independently of testosterone to modulate vocal control region (VCR) volumes in adult songbirds. In the present study, we investigated the effects of testosterone and photoperiod on the volumes of four VCRs in adolescent male juncos. To test the hypothesis that VCR volumes in these males are testosterone independent, we treated birds exposed to short days with testosterone and later compared their VCR volumes with those of birds exposed to short days without testosterone. To examine whether photoperiod alone could affect VCR volumes independent of testosterone, we measured these volumes in photorefractory birds exposed to long photoperiod without testosterone. Administering testosterone induced singing, yet increased the volume of only one VCR, the robust nucleus of the anterior neostriatum (RA). In contrast, long photoperiod increased several VCR volumes (Area X, higher vocal center, and RA) despite low testosterone levels, but did not induce singing. Our results suggest a limited role for testosterone, but an important role for photoperiod, in controlling VCR volumes in adolescent male juncos. In addition, the results demonstrate that singing behavior can be induced in adolescent males without a concomitant increase in most VCR volumes.

Animals↗

[Serum and salivary testosterone levels in erectile dysfunction].

In this study 66 male patients with erectile dysfunction were investigated. The authors measured the testosterone levels in serum and in saliva, which latter represent with good accuracy the serum levels of free testosterone. The mean serum total testosterone level was 17.6 nmol/L (confidence intervals: 15.5 and 20.2 nmol/L, normal range: 10-50 nmol/L). The mean salivary free testosterone level was 218.5 pmol/L (confidence intervals: 198.3 and 239.9 pmol/L, normal range: 200-1000 pmol/L). Low salivary (free) testosterone levels were found in 36.4% of patients, while only in 10.6% of patients had low serum testosterone levels (p = 0.01, by binomial test). Although there is a relationship between serum and salivary testosterone levels (r = 0.41, p < 0.001), the patients with low salivary (free) testosterone levels have in major part a normal serum total testosterone level. These data indicate that a considerable proportion of patients with erectile dysfunction have androgen deficiency. The serum total testosterone level is not a sensitive indicator to detection of hypogonadism. The androgen substitution therapy has a beneficial effect on erectile dysfunction in a significant part of patients. The measurement of free testosterone level in saliva may have an important role both in the diagnosis of diseases characterized by androgen deficiency and hyperandrogenic status.

Adult↗

Testosterone and social and reproductive behaviour in Aphelocoma jays.

When there is a direct relationship between testosterone level and payoff in reproductive success through aggression, testosterone levels should be elevated. Elevated testosterone, however, has fitness costs, particularly a decreased tendency to display parental care. Thus the pattern of testosterone secretion in males should vary with the social and mating system. Western scrub-jays, Aphelocoma californica woodhouseii, form monogamous pairs on territories during the breeding season. Mexican jays, A. ultramarina, live in large, stable groups and up to five females within a group attempt nesting each spring. In both species, testosterone levels rose rapidly in March and peak levels did not differ. Elevated testosterone levels were only observed for about 3 weeks in the monogamous western scrub-jay, but were observed into May in Mexican jays, a reflection of prolonged opportunity for males to mate with multiple females and continual interaction with other competing males. In Mexican jays, nonbreeding yearlings had lower testosterone levels than all other age groups. Testosterone in males owning nests did not differ from that in other adult males, many of whom engage in extrapair fertilizations. Testosterone was elevated throughout the incubation phase, but was significantly lower when chicks were present in any nest in the group. Nearly all birds in the group fed all chicks. These observations support the hypothesis that testosterone is elevated when male-male competition is frequent and mating opportunities depend on the outcome of that competition, and testosterone is decreased when the necessity for parental or alloparental care would make its effects deleterious. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

Testosterone secretion during early pregnancy in mares.

We have characterized the testosterone secretion pattern during the first 80 d of pregnancy in mares and determined the sources that contribute to circulating testosterone levels during this period. Ten untreated, pregnant mares (Group 1), 10 altrenogest-treated, pregnant mares (Group 2), and 10 altrenogest-treated, pregnant mares in which the CL was eliminated by administration of PGF-2alpha on Day 16 (Group 3) were used in this study. Complete luteolysis occurred following PGF-2alpha administration in all mares in Group 3. Six of the 10 mares in Group 3 did not have an active CL until after Day 60 of pregnancy (Group 3a) and were included in the analysis. The remaining four mares developed a new CL on Days 32, 40, 43 and 49 of pregnancy and were excluded from analysis. Mares without a functional CL (Group 3a) had significantly lower testosterone concentrations than mares with a functional CL (Groups 1 and 2), during the period before equine chorionic gonadotropin (eCG) secretion. At the onset of eCG secretion, testosterone concentrations increased rapidly but the rate of increase decreased with time in mares with a functional CL (Groups 1 and 2). In mares without a functional CL (Group 3a), testosterone concentrations did not increase at the onset of eCG secretion but increased at a gradually increasing rate after Day 50. The lower testosterone concentration in mares without a functional CL before eCG secretion suggests that the CL contributes significantly to the circulating testosterone concentration during the period before eCG secretion. The close time relationship between the onset of eCG secretion and the increase in testosterone secretion in mares with a functional CL and the lack of a testosterone increase in pregnant mares without a functional CL suggest that the increase in testosterone secretion after Day 35 of pregnancy is the result of eCG-stimulated, luteal testosterone synthesis.

Journal Article↗

Development of basal and induced testosterone hydroxylase activity in the chicken embryo in ovo.

1. The sensitivity of the developing embryo to xenobiotics is highly dependent on the expression of metabolizing enzymes including cytochromes P450 (CYP). In the present study, therefore, the ontogeny of the CYP-dependent system in the chick was investigated with testosterone hydroxylase activity as a marker of CYP expression. 2. Chicken embryo livers were assayed for basal and phenobarbitone (PB)-induced regio- and stereo-selective testosterone hydroxylase activity, from the first appearance of the liver as a discrete organ at 5 days of incubation through day 10 posthatching. In addition, whole embryo preparations were assayed at 3 and 4 days of incubation. 3. Whereas testosterone 16 beta-hydroxylase and androst-4-ene-3, 17-dione-linked activities were expressed during all stages of embryonic development, testosterone 6 alpha-, 6 beta-, 7 alpha- and 16 alpha-hydroxylase activities were observed only in basal embryos from 8 days of incubation. Furthermore, testosterone 2 alpha- and 2 beta-hydroxylase activities were detected exclusively from 10 days of incubation onward. All activities increased steadily throughout development as did the responsiveness of the embryonic liver to PB induction. 4. A typical pattern of development with a higher activity from 10 to 14 days of incubation (testosterone 16 alpha-, 7 alpha-, 6 alpha- and 2 beta-hydroxylase activities; up to 4.1 +/- 0.3 pmol mg-1 protein min-1 at 13 days of incubation for testosterone 7 alpha-hydroxylase) or shifted to 14 to 18 days of incubation (testosterone 6 beta-, 2 alpha- and 16 beta-hydroxylase activities: up to 56.6 +/- 1.4 pmol mg-1 protein min-1 at 16 days of incubation for testosterone 6 beta-hydroxylase) was observed. There was a tendency towards an increased activity for all activities around hatching, specifically from 19 days of incubation to 4 days posthatching (up to 1,759.3 +/- 179.4 pmol mg-1 protein min-1 at 1 day posthatching for androst-4-ene-3,17-dione-linked activity). 5. The highest level of PB-induced enzyme activity was observed for testosterone 2 alpha-hydroxylase activity (95.14 +/- 7.35 and 660.19 +/- 45.27 pmol mg-1 protein min-1) at 12 days of incubation and day 3 posthatching, respectively. Except for testosterone 2 alpha- and 2 beta-hydroxylase activities at 3 to 4 days of incubation, all metabolites were detectable during the first period of organogenesis in the presence of PB. 6. The use of highly specific substrates, studies on the immunoinhibition of metabolism by polyclonal antibodies raised against highly purified rat CYPs, and the use of selective inhibitors seemed to reveal a wide pleiotropic response with the possible presence in liver of PB-treated chickens of CYP1A together with CYP2HI/H2, CYP2E and CYP3A.

Animals↗

Effects of testosterone administration in human immunodeficiency virus-infected women with low weight: a randomized placebo-controlled study.

BACKGROUND: The prevalence of human immunodeficiency virus (HIV) disease is increasing among women, many of whom remain symptomatic with low weight and poor functional status. Although androgen levels may often be reduced in such patients, the safety, tolerability, and efficacy of testosterone administration in this population remains unknown. METHODS: A total of 57 HIV-infected women with free testosterone levels less than the median of the reference range and weight less than 90% of ideal body weight or weight loss greater than 10% were randomly assigned to receive transdermal testosterone (4 mg/patch) twice weekly or placebo for 6 months. Muscle mass was assessed by urinary creatinine excretion. Muscle function was assessed by the Tufts Quantitative Muscle Function Test. Treatment effect at 6 months was determined by analysis of covariance. Results are mean +/- SEM unless otherwise specified. RESULTS: At baseline, subjects were low weight (body mass index [calculated as weight in kilograms divided by the square of height in meters] 20.6 +/- 0.4), with significant weight loss from pre-illness maximum weight (18.7% +/- 1.2%), and demonstrated reduced muscle function (upper and lower extremity muscle strength, 83% and 67%, respectively, of predicted range). Testosterone treatment resulted in significant increases in testosterone levels vs placebo (total testosterone: 37 +/- 5 vs -2 +/- 2 ng/dL [1.3 +/- 0.2 vs -0.1 +/- 0.1 nmol/L] [P<.001]; free testosterone: 3.7 +/- 0.5 vs -0.4 +/- 0.3 pg/mL [12.8 +/- 1.7 vs -1.4 vs 1.0 pmol/L] [P<.001]) and was well tolerated, without adverse effects on immune function, lipid and glucose levels, liver function, or body composition or the adverse effect of hirsutism. Muscle mass tended to increase (1.4 +/- 0.6 vs 0.3 +/- 0.8 kg; P =.08), and shoulder flexion (0.4 +/- 0.3 vs -0.5 +/- 0.3 kg; P =.02), elbow flexion (0.3 +/- 0.4 vs -0.7 +/- 0.4 kg; P =.04), knee extension (0.2 +/- 1.0 vs -1.7 +/- 1.3 kg; P =.02), and knee flexion (0.7 +/- 0.5 vs 0.3 +/- 0.7 kg; P =.04) increased in the testosterone-treated compared with the placebo-treated subjects. CONCLUSIONS: Testosterone administration is well-tolerated and increases muscle strength in low-weight HIV-infected women. Testosterone administration may be a useful adjunctive therapy to maintain muscle function in symptomatic HIV-infected women.

Adult↗

Time course of effects of testosterone administration on sexual arousal in women.

BACKGROUND: The assumption that testosterone is involved in human female sexual functioning is mainly based on results of studies of women with hypogonadotropic hypogonadism. This study sought to determine the effect of testosterone administration on physiological and subjective sexual arousal in sexually functional women. METHODS: In a double-masked, randomly assigned, placebo-controlled crossover design, we examined whether administration of a single dose of testosterone to sexually functional women increases vaginal and subjective sexual arousal when they are exposed to erotic visual stimuli. To search for a time lag in the effect of testosterone therapy, we exposed 8 healthy women to 6 erotic film excerpts depicting intercourse. The first and second excerpts were shown immediately before and 15 minutes after, respectively, intake of placebo or testosterone; the last 4 excerpts were then shown at 1(1/2)-hour intervals. RESULTS: Sublingual intake of testosterone caused a sharp increase in plasma testosterone levels within 15 minutes; these levels declined to baseline values within 90 minutes. Three to 4(1/2) hours after reaching peak testosterone level, we found a statistically significantly increase in genital responsiveness (P = .04). Furthermore, on the day of testosterone treatment, there also was a strong and statistically significant association between the increase in genital arousal and subjective reports of "genital sensations" (P = .02) and "sexual lust" (P = .01) after 4(1/2) hours. CONCLUSIONS: There is a time lag in the effect of sublingually administered testosterone on genital arousal in women. In addition, a consecutive increase in vaginal arousal might cause higher genital sensations and sexual lust.

Administration, Sublingual↗

Increased plasma and pituitary prolactin concentrations in adult male rats with selective elevation of FSH levels may be explained by reduced testosterone and increased estradiol production.

The roles of testosterone and estradiol in regulating prolactin concentrations were studied in acutely castrated adult male rats receiving subcutaneous Silastic implants of the sex steroids. Testosterone was administered in increasing doses, from subphysiologic to intact levels, both alone and in combination with a small, single dose of estradiol. The study was designed to assess whether a change in the relative rates of sex steroid production could account for an increase in PRL release in the absence of other testicular factors. At very low levels of plasma testosterone, FSH and LH levels were indistinguishable from castrate controls. As plasma testosterone concentration increased, both plasma FSH and LH levels were suppressed progressively to intact levels. When a subphysiologic dose of testosterone was coadministered with a small dose of estradiol, the combined effects produced a midcastrate level of FSH but maintained a normal level of LH similar to the selective increase in FSH concentration observed in men with germinal aplasia. Although PRL levels were indistinguishable in intact and castrate controls, testosterone replacement by capsule increased prolactin in a dose-related manner so that, at the physiologic level of testosterone, prolactin was elevated two-fold (P less than 0.01), similar to the level achieved with estradiol replacement alone. Pituitary prolactin levels also increased with increasing doses of testosterone but values remained within the range measured in intact controls. When estradiol was coadministered with testosterone, the combination produced different effects depending on the testosterone dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of testicular interstitial macrophages in regulating testosterone release in hyperprolactinemia.

Hyperprolactinemia-induced hypogonadism has been linked to a dysfunction of the hypothalamus-pituitary-testis axis. The direct inhibitory effects of prolactin on the testicular release of testosterone have also been demonstrated, though their mechanisms remain unclear. Incubation of rat testicular interstitial cells (TICs) with prolactin stimulated the release of testosterone. TICs from rats with anterior pituitary-grafting-induced hyperprolactinemia release lower amounts of testosterone than controls. However, Leydig cells isolated from anterior pituitary-grafted rats release a greater amount of testosterone. These paradoxical observations have remained unexplained. This study examined the roles of testicular interstitial macrophages and of their product, tumor necrosis factor-alpha (TNF-alpha), in regulating Leydig cells under condition of hyperprolactinemia. Hyperprolactinemia was induced by grafting two anterior pituitary glands of rats under the renal capsule. Control animals were grafted with rat cortex tissue. The rats were sacrificed 6 weeks later. TICs and macrophages, and Leydig cells were isolated for in vitro incubation and drugs challenge. Testosterone released by testicular interstitial or Leydig cells was measured by radioimmunoassay. TNF-alpha concentration in the medium of TICs or macrophages was measured by enzyme-linked immunosorbent assay (ELISA). A dose-dependent stimulation of TNF-alpha secretion in the medium of TICs or macrophages by the prolactin challenge was observed. Higher amounts of TNF-alpha were released by TICs in the anterior pituitary-grafted rats than in the control group. In contrast, the release of TNF-alpha by testicular interstitial macrophages isolated from the anterior pituitary- and cortex-grafted groups was quantitatively similar. Challenge with human chorionic gonadotropin did not modify the TNF-alpha release by testicular interstitial macrophages in either group. Challenge of Leydig cells with TNF-alpha inhibited their release of testosterone stimulated by human chorionic gonadotropin, but not their basal testosterone release. These different patterns of testosterone release in TICs versus Leydig cells cultures in anterior pituitary-grafted rats may be due to the influence of testicular interstitial macrophages. These observations correlate with in vivo conditions, where prolactin increases the release of TNF-alpha by testicular interstitial macrophages, which, in turn, decreases the human chorionic gonadotropin-stimulated release of testosterone by Leydig cells. In summary, hyperprolactinemia-induced hypogonadism involves a mechanism of prolactin-originated, macrophage-mediated inhibitory regulation of testosterone release by Leydig cells. TNF-alpha, one of the cytokines secreted by macrophages, may play a key role in this mechanism.

Animals↗

Effect of exogenous testosterone replacement on prostate-specific antigen and prostate-specific membrane antigen levels in hypogonadal men.

Previous studies have suggested that serum prostate-specific antigen (PSA) levels are under androgenic influence, especially in patients with adenocarcinoma of the prostate. PSMA (prostate-specific membrane antigen) is thought to reflect hormonal or clonal resistance or an independence with respect to testosterone regulation. The influence of testosterone on serum PSA expression in normal men is not clear. We studied the effect of exogenous testosterone administration on the serum levels of PSA and PSMA in hypogonadal men. Serial serum PSA, serum PSMA by Western blot, and serum total testosterone levels were obtained at intervals of every 2-4 weeks in 10 hypogonadal men undergoing treatment with exogenous testosterone, delivered as testosterone enanthate injection or by testosterone patch. Linear and quadratic orthogonal polynomial scores were calculated for PSMA, PSA, and testosterone. A 2-tailed, paired t-test failed to demonstrate a significant correlation between serum PSA (linear P = 0.432, quadratic P = 0.290) or PSMA (linear P = 0.162, quadratic P = 0.973) and serum testosterone levels. This study suggests that in hypogonadal men, neither PSMA nor PSA expression is testosterone-dependent.

Adult↗

Testosterone treatment results in quiescent satellite cells being activated and recruited into cell cycle in rat levator ani muscle.

At puberty, the male levator ani (LA) muscle exhibits muscle fiber hypertrophy. This fiber enlargement can be provoked in the female LA muscle by testosterone treatment. In both cases the hypertrophic process is accompanied by an increase in the number of satellite cells and myonuclei. The present ultrastructural autoradiographic study was undertaken in order to investigate (1) whether satellite cells when stimulated by testosterone can undergo DNA synthesis by incorporating [3H]thymidine ([3H]Tdr); (2) whether the whole satellite cell population is committed in the cell cycle; and (3) whether the new myonuclei originate from fusion of the satellite cells with the preexistant myofibers. Thirty-day-old female rats treated with a single testosterone injection received a single injection of [3H]Tdr at 24, 28, 32, to 34 hr after testosterone treatment. LA muscles were removed 2 hr after [3H]Tdr injection. This first series of experiments allowed us to determine that onset of DNA synthesis in satellite cells occurs within the 34th and the 36th hour after testosterone treatment. To obtain a more precise timing, 30-day-old female rats treated with a single testosterone injection received multiple injections every 30 min either from Hour 32 to 33.5 or from Hour 34 to 35.5 LA muscles were removed 30 min after the last [3H]Tdr injection. This showed that the onset of satellite cell replication occurred between the 32nd and the 34th hour after testosterone treatment. However, only 30% of the satellite cell population was affected by this proliferative process regardless of the experimental protocol used. To confirm that the increase in myonuclei number results from incorporation of satellite cells into mature myofibers, 30-day-old female rats treated with a single injection of testosterone received a single injection of [3H]Tdr on the 60th hour after testosterone treatment. LA muscles were removed at 63, 84, to 108 hr after [3H]Tdr injection. We conclude that testosterone induces satellite cell proliferation at around the 33rd hour and that the increased number of myonuclei reported in our previous study is due to fusion of labeled satellite cells with myofibers.

Animals↗

The effect of chronic testosterone administration on sturgeon gonadotropins in juvenile and pre-vitellogenic white sturgeon (Acipenser transmontanus).

The effects of chronic exogenous testosterone treatment on the synthesis and/or secretion of two sturgeon gonadotropins (stGTH I and stGTH II) were assessed in 2-year-old juvenile white sturgeon (Acipenser transmontanus) surgically implanted with silastic capsules filled with 75 mg of testosterone and in previtellogenic female white sturgeon females implanted with 150 mg of testosterone. In groups of juvenile white sturgeon sacrificed 30, 60, 90, or 442 days postimplantation, pituitary concentrations of stGTH I were significantly greater in testosterone-treated fish (P < 0.01) when compared to those of controls. Pituitary concentrations of stGTH II were significantly higher (P < 0.01) in juvenile fish treated 60, 90, or 442 days with testosterone when compared to those of controls. Exogenous testosterone had no effect on plasma concentrations of either stGTH. Additional testosterone-treated juvenile sturgeon which were injected intraperitoneally 90 or 442 days postimplantation with 10 microg/kg of the gonadotropin releasing hormone analog d-Ala6-des-Gly10-GnRH ethylamide (GnRHa) also showed no change in plasma concentrations of stGTHs. Similar results were obtained for previtellogenic white sturgeon, as pituitary concentrations of stGTH I and stGTH II were significantly greater (P < 0.01) after 60 days of testosterone treatment compared to those of controls. A second group of 60-day testosterone-treated previtellogenic females also failed to exhibit increases of plasma stGTHs when administered 10 microg/kg of GnRHa. These results indicate that long-term testosterone treatment stimulates the accumulation of pituitary stGTHs in both juvenile and previtellogenic white sturgeon but does not affect basal or GnRHa-induced stGTH secretion.

Animals↗

Physiological levels of testosterone kill salmonid leukocytes in vitro.

Adult spring chinook salmon (Oncorhynchus tshawytscha) elaborate high plasma concentrations of testosterone during sexual maturation, and these levels of testosterone have been shown to reduce the salmonid immune response in vitro. Our search for the mechanism of testosterone's immunosuppressive action has led to the characterization of an androgen receptor in salmonid leukocytes. In the present study we examined the specific effects that testosterone had on salmonid leukocytes. Direct counts of viable leukocytes after incubation with and without physiological levels of testosterone demonstrate a significant loss of leukocytes in cultures exposed to testosterone. At least 5 days of contact with testosterone was required to produce significant immunosuppression and addition of a "conditioned media" (supernatant from proliferating lymphocytes not exposed to testosterone) did not reverse the immunosuppressive effects of testosterone. These data lead us to conclude that testosterone may exert its immunosuppressive effects by direct action on salmonid leukocytes, through the androgen receptor described, and that this action leads to the death of a significant number of these leukocytes.

Animals↗

Effects of experimentally elevated testosterone on plasma corticosterone and corticosteroid-binding globulin in dark-eyed juncos (Junco hyemalis).

An earlier study of free-living male dark-eyed juncos found an increase in plasma corticosterone (B) in response to experimental elevation of plasma testosterone (T) (E. D. Ketterson et al., 1991, Horm. Behav. 25, 489-503). To investigate whether the increase was caused by enhanced secretion of corticosterone or by a slower clearance rate, or both, we exposed 52 captive yearling male dark-eyed juncos (Junco hyemalis) to day lengths corresponding to those of spring and implanted them with one or two testosterone-filled or sham implants (10 T-I, 22 T-II, and 20 C-males). We then examined the effect of experimentally elevated testosterone on plasma corticosterone and on corticosteroid-binding globulin (CBG), as measured by the ability of steroid-stripped plasma to bind labeled corticosterone. Plasma samples were taken five times, 2 weeks before experimental prolongation of day length and approximately every 3 weeks thereafter. Treatment with testosterone increased both plasma testosterone and plasma corticosterone two to three times above control levels, and the degree of elevation was dose-dependent. Only when all treatment groups were pooled, however, were plasma testosterone and corticosterone significantly correlated. The relationship between plasma corticosterone and time required to bleed the birds was similar for all three treatment groups, suggesting that there was no effect of treatment on the stress response. Testosterone significantly increased the capacity of the plasma to bind corticosterone, presumably because it contained more CBG, when compared to the plasma of controls. However, treatment with testosterone did not affect the affinity of the plasma for corticosterone. It seems likely that exogenous testosterone elevated corticosterone by slowing the corticosterone clearance rate via an increase in CBG. It is not clear what the net effect of chronic elevation of testosterone would be on the availability of corticosterone to target tissues.

Animals↗

Expression of testosterone conditioned place preference is blocked by peripheral or intra-accumbens injection of alpha-flupenthixol.

Previous evidence indicates that peripheral and intranucleus accumbens injections of testosterone have rewarding effects in male rats as measured in a conditioned place preference (CPP) paradigm. The present study investigated the neurochemical bases of the rewarding properties of testosterone by examining the effect of peripheral and intranucleus accumbens injection of the dopamine receptor antagonist alpha-flupenthixol on expression of testosterone-induced CPP. On alternating days, adult male Long-Evans rats received peripheral injections of testosterone in a water-soluble hydroxypropyl-beta-cyclodextrin (HBC) inclusion complex (0.8 mg/kg) or saline-HBC immediately prior to being confined for 30 min to one of two compartments of a place preference apparatus. All rats received 8 days of pairings (four hormone pairings, four saline pairings). On day 9 the rats were given a 20-min test session during which they had access to all compartments of the apparatus. No hormone was injected prior to the test session; however, rats received a peripheral (20 min prior; 0.2, 0.3 mg/kg) or intra-accumbens (2 min prior, 5.0 micrograms) injection of alpha-flupenthixol or saline. On the test day, rats receiving saline injections spent significantly more time in the compartment previously paired with injections of testosterone than in the compartment previously paired with vehicle injections. In contrast, rats receiving peripheral or intra-accumbens alpha-flupenthixol injections did not spend significantly more time in the compartment previously paired with testosterone. The blockade of testosterone CPP was not due to an effect of alpha-flupenthixol on motor behavior. The findings provide further evidence of the rewarding affective properties of testosterone and indicate that peripheral administration and intra-accumbens administration of alpha-flupenthixol block expression of testosterone CPP. The rewarding affective properties of testosterone are mediated, at least in part, via an interaction with the mesolimbic dopamine system.

Animals↗

Individual and seasonal variation in fecal testosterone and cortisol levels of wild male tufted capuchin monkeys, Cebus apella nigritus.

This study tested the "challenge hypothesis" and rank-based predictions for temporal steroid production in male tufted capuchin monkeys, Cebus apella. Fecal samples (n = 209) collected from six wild males were analyzed for testosterone and cortisol concentration by enzyme immunoassay. The temporal pattern in male steroid production was compared to female sexual activity and rates of male aggression. The top-ranking adult male did not differ from other adult males in testosterone or cortisol concentration. Mean adult testosterone was significantly higher than mean subadult testosterone throughout the year. There was a clear elevation of testosterone and cortisol in both adult and subadult males during the peak of adult female sexual activity after the birth season. In fact, the magnitude of increase in testosterone was higher than predicted for a species with low male-male aggression. However, there was no difference between nonbreeding baseline testosterone levels during the birth season, and the "breeding" baseline of testosterone in males found during asynchronous female sexual activity. Of all behavioral indices examined, the distribution of female-maintained consortships was the best predictor of mean adult male testosterone concentrations. Although in many species, elevated testosterone coincides with increased male-male aggression, in the present study, the sustained high-magnitude increase in steroids during the peak of adult female sexual activity was associated with a relatively low rate of male-male intragroup aggression.

Age Factors↗