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PubMed1979

Evaluation of various doses of testosterone on accessory reproductive organs and plasma testosterone in intact and gonadectomized rhesus monkeys (Macaca mulatta).

The effect of 10 days i.m. treatment of testosterone propionate (TP) on plasma testosterone and accessory reproductive organs were studied in adult (6 to 6 1/2 kg) male rhesus monkeys, housed under natural light conditions using six different dose levels. The study was scheduled in the month of September and October. To maintain the weight of accessory reproductive organs and testosterone levels in castrates, different dose levels of exogenous testosterone propionate were required: 3.2 mg/d for seminal vesicles, 4.8 mg/d for ventral prostate and 3.2 mg/d for plasma testosterone titer. The levels of so-called "physiological" doses of exogenous testosterone varied for various target organs under consideration. TP at a dose of 0.4 mg/d had a depressing effect on plasma testosterone in intact monkeys. For higher doses, plasma testosterone increased roughly similarly in both intact and castrated monkeys. It suggests that with otherwise "physiological" doses of testosterone propionate, there is an almost complete blockage of endogenous testosterone secretion.

Animals↗
PubMed1977

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↗
PubMed2006

Vaginal application of testosterone: A study on pharmacokinetics and the sexual response in healthy volunteers.

INTRODUCTION: Androgen substitution is advocated to improve sexual functioning in women with androgen insufficiency. Nevertheless, the role of androgens in female sexual functioning is not yet unraveled. Even less is known about changes in androgens and the female sexual response. AIM: The aim of the study is to describe the pharmacokinetics of a single dose of vaginally applied testosterone. In addition, the study aims to gain more insight into the relation between acute changes in testosterone levels and the sexual response in women. METHODS: A randomized, double-blind, crossover study design was used to compare a single vaginal dose of testosterone propionate (2 mg) with placebo. Ten healthy premenopausal women participated. Serum levels of testosterone, free testosterone, and estradiol were measured. The sexual response was measured before application of medication and 4 and 8 hours after application. Erotic video fragments and erotic fantasies were used as stimuli. The genital sexual response was measured using vaginal plethysmography. The subjective sexual response was measured using a visual analog scale. RESULTS: Vaginal administration of testosterone propionate induced a significant rise in serum testosterone levels and free testosterone levels, but not in serum estradiol levels. Peak levels were reached after 5.5 hours (range 2-12 hours). Mean peak levels of testosterone were 7.71 nmol/L after testosterone propionate and 2.99 nmol/L after placebo (P < 0.005). Mean peak levels of free testosterone were 0.12 nmol/L after testosterone propionate and 0.04 nmol/L after placebo (P < 0.005). Despite marked elevated levels of androgens this study was unable to detect a direct effect on the genital or subjective sexual response. CONCLUSIONS: A single dose of vaginally applied testosterone propionate elevates serum levels of testosterone and free testosterone within 6 hours. Nevertheless, this acute rise in androgens has no effects on the female sexual response.

Administration, Intravaginal↗
PubMed1994

Serotonergic control of androgen-induced dominance.

The present study investigates the role of serotonergic systems in anabolic steroid-induced aggression. An animal model of aggressive dominance was used to assess the chronic effects of testosterone propionate. When rats that had become dominant following administration of testosterone propionate received serotonergic agonists with selectivity for the 5-HT1A receptor (8-OH-DPAT, buspirone, gepirone), the 5-H1B receptor (eltoprazine, TFMPP), or the 5-HT2A/2C receptor (DOM), a dose-dependent decrease in dominance was demonstrated. Pretreatment with three serotonergic antagonists (pizotyline, pirenpirone, and pindolol) blocked agonist-induced reductions in dominance in varying degrees. Nonserotonergic agonists with CNS depressant effects were also tested in dominant animals. The benzodiazepine, chlordiazepoxide, did not reduce dominance except at doses that interfered with motor behavior. The opioid agonist, morphine, dose dependently decreased dominance, but this effect was reversible with administration of the serotonergic antagonist, pirenpirone, suggesting the antidominant effect of morphine had a serotonergic component. Biochemical experiments demonstrated that following chronic testosterone propionate, there was a decrease in levels of 5-HT and 5-HIAA in the hippocampus but not in the striatum or the frontal cortex. Chronic testosterone propionate also caused an increase in the affinity of [3H]8-OH-DPAT for the 5-HT1A receptor but no corresponding change in the density of 5-HT1A binding sites in the hippocampus. There was also no change in the properties of the 5-HT2 receptor in the frontal cortex following chronic testosterone propionate. These data suggest that serotonergic systems may play an important role in the control of anabolic steroid-induced aggressive dominance.

Aggression↗
PubMed1981

Detection of estrus with cows administered testosterone via injections and/or silastic implants.

Over a three year period 8 cows and 2 heifers were administered testosterone via injections and/or silastic implants. During and subsequent to treatments, blood samples were collected for determination of testosterone and cows were observed for male sex behavior. Male sex behavior was induced by administering 200 mg of testosterone propionate every other day for 20 days, and once induced, male sex behavior was maintained by injections of 200 mg of testosterone propionate every 10 days or by two 15 cm silastic implants containing testosterone propionate. Male sex behavior was also induced and maintained by administering an injection of testosterone enanthate (1 gm) and testosterone propionate (200 mg) and two 15 cm silastic implants containing testosterone propionate at the same time. Cows which are administered testosterone in this manner detected 94% of 231 females that were in estrus 342 times.

Journal Article↗
PubMed1986

Uterine position and the activation of male sexual activity in testosterone propionate-treated female guinea pigs.

Fetal female guinea pigs were delivered surgically and their position within a uterine horn relative to male fetuses was noted. When adult they were ovariectomized, injected daily with testosterone propionate, and examined for male copulatory behaviors in response to the presence of a receptive female. Females that developed contiguous to a caudal male were functionally similar to those that had been situated between two males; both exhibited enhanced levels of mounting relative to females that were located contiguous to no males (with and without the presence of a caudal male) and to females contiguous to a cephalic male. Therefore, both contiguity and positioning of the male fetus are necessary conditions for prenatal masculinization of the female guinea pig. Lastly, four animals that had resided singly in the uterus displayed the lowest levels of copulatory behaviors.

Animals↗
PubMedDate not supplied

Effects of depot testosterone administration on serum levels of testosterone, FSH, LH and prolactin.

The effects of the administration of testosterone on plasma testosterone (T), estradiol (E), FSH, LH and prolactin (PRL) were tested in a group of men, aged over sixty. Blood samples were collected on the 2nd, 4th, 7th and 15th day afterr the administration of testosterone propionate (TP) (n = 28 men) and testosterone propionate with testosterone enantate (TP + TE) (n = 21 men). After the administration of TP + TE plasma T increased on days 2-4, returned to the normal basal level on the 7th day, and rose again on the 15th day. With the TP preparation the levels of testosterone remained elevated during the first seven days and returned to the basal values by the 15th day. The FSH and LH were suppressed during the first seven days after the injection of both TP and TP + TE preparations. On the 15th day gonadotropins were suppressed only by the administration of TP. The plasma concentration of E behaved like that of T. We found a significant increase in the PRL levels on the 4th day after treatment with 100 mg of the two preparations. Moreover, we found that PRL basal values were significantly higher in those subjects whose T basal values were low.

Aged↗
PubMed1953

Quantitative studies of prostatic secretion. III. Simultaneous measurement of size and secretion of the canine prostate and the interaction of androgenic and estrogenic substances thereon.

The prostate of the dog was relocated permanently in the perineum where its size could be measured and correlated with the output of prostatic secretion during many months. The secretion of a submaxillary gland obtained through a fistula was utilized as an internal biologic standard of the effects of pilocarpine, the secretory stimulus employed, because the amount and route of administration of the alkaloid are critical factors in inducing secretion. Prostatic secretion was found to be profoundly affected by androgenic and estrogenic compounds, in contrast to salivation. The curves of the secretory response of the prostate and submaxillary glands to pilocarpine proved to be similar and a mathematical formula has been constructed to represent them. When testosterone propionate was administered in increasing quantities for periods of weeks at each level, the volume of the prostate increased in a series of flattened curves. This volume, under the conditions mentioned, was found to stand in a simple arithmetic relationship to the amount of testosterone propionate administered. Moderate quantities of testosterone propionate masked the effects of small amounts of stilbestrol on the prostate. The reverse was also true and the critical amounts of these compounds were defined. The amounts of stilbestrol were determined which lowered the quantity of prostatic secretion resulting from the simultaneous administration of moderate amounts of testosterone propionate in castrate dogs, the result being a level and flat secretory curve which was maintained for many weeks. We designate this effect the plateau phenomenon. When this amount of estrogen was continued, and the dosage of testosterone propionate greatly augmented, the prostatic secretion did not increase in volume. Very slight increases above the critical amount of stilbestrol, however, caused the secretory curve to fall to new and still lower levels though the secretion was never completely suppressed. The acid phosphatase content of the prostatic secretion in the regions of secretory plateaus was similar to that of castrate dogs injected with androgen alone. The plateau phenomenon is due to simultaneous physiologic action of androgenic and estrogenic compounds on the prostatic cells. The depression of prostatic secretion resulting in the plateau phenomenon is due to both functional and structural changes in the prostatic epithelium. They are best explained on the assumption that differences in steroid threshold exist in groups of cells within the prostate, those of the anterior rim of the gland being least susceptible to estrogenic activity.

Androgens↗
PubMed1992

Androgenic control of polyamine concentrations in rat epididymis.

Unilateral orchidectomy resulted in a significant decrease in tissue content of putrescine and polyamines. However, no differences were detected when the results were expressed in terms of ng g-1 tissue. At 48 h after bilateral orchidectomy, a significant decrease in putrescine content was observed, but spermidine and spermine content were unaffected. The observed decrease in putrescine was prevented by treatment with testosterone propionate, but neither spermidine nor spermine were affected. Bilateral orchidectomy resulted in a significant decrease in the tissue content of putrescine, spermidine and spermine after 7 days. Treatment with testosterone propionate increased the content of putrescine, spermidine and spermine in the epididymis by about 200%, 92% and 34%, respectively. When results were expressed as nmol g-1, a significant decrease after castration in putrescine and spermidine, but not in spermine, was observed. Treatment with testosterone propionate restored putrescine concentration, but had no effect on spermidine and spermine concentrations. In castrated rats treated with testosterone propionate, the anti-androgen flutamide abolished the effect of the androgen on putrescine and spermidine content, but there was no effect on spermine. Acetylputrescine was not detected in the epididymis, while acetylpolyamines were detected at much lower concentrations than polyamines. After bilateral orchidectomy there was a decrease in the tissue content of all acetylpolyamines and an increase in their tissue concentration. The effect of castration on acetylpolyamine content was reversed by testosterone propionate treatment. We conclude that an active synthesis of polyamines occurs in the rat epididymis, and that this process depends upon the androgen environment. Regulation of ornithine decarboxylase activity appears to be the main step that is controlled by androgens.

Androgens↗
PubMed1986

Social behaviour and testicular activity of juvenile rats.

The juvenile stage of ontogeny is often characterized as a time of inactivity and quiescence for the immature reproductive system. The principle social behaviour by juveniles of many mammalian species is a rough-and-tumble activity known as play-fighting. An experiment is reported in which play-fighting by male rats was observed after various manipulations of gonadal steroids. Rats were housed in groups and castrated either on day 1 or day 10, times which are respectively during and after the sensitive period for androgen-induced organization of neural tissues in rats. Animals were injected with either 40 micrograms testosterone propionate or vehicle between 21 and 45 days of age, and play-fighting with unoperated, unfamiliar rats was examined. Castration on days 1 and 10 suppressed play-fighting. The behaviours remained suppressed in rats castrated on day 1 and injected with testosterone propionate, but testosterone propionate restored play-fighting to near-normal levels until 35 days of age in rats castrated on day 10. Moreover, gonadally intact juvenile males exposed to the androgen antagonist flutamide play-fought less than intact control males, although their social activity increased appreciably after day 35. It is concluded that the juvenile is not experiencing endocrine quiescence. Behavioural and physiological data suggest a reproductive system which is active, although differently from that in the adult. Hypersensitivity to testosterone and surges of gonadotrophin-releasing factors and LH at 35 days of age may be the events responsible for changes in play-fighting resulting from manipulations of gonadal steroids in juvenile rats.

Animals↗
PubMed1978

Testosterone-induced focal myocarditis in rats. I. Morphological and biochemical studies with special reference to pathogenetical mechanism and species differences.

Focal myocarditis characterized by interstitial edema, round cell infiltration and fibrosis occurred in rats given a subcutaneous administration of testosterone propionate in a dose of 50 mg/kg for 30 consecutive days or longer. Biochemical analysis showed a two to five time increase of deoxycorticosterone and a moderate decrease of corticosterone in blood plasma of these rats as well as in those treated with 50 mg/kg of testosterone propionate for 15 days. It was also shown that myocarditis did not occur in adrenalectomized rats after administration of testosterone propionate 50 mg/kg for 30 days, while subcutaneous injections of deoxycorticosterone acetate in a dose of 15 mg/kg for 30 days invariably produced cardiac lesions in both adrenalectomized rats and sham-operated rats. Regarding species difference, administration of testosterone did not produced either a high blood level of deoxycorticosterone or focal myocarditis in guinea pigs or rabbits. From these results, it is concluded that focal myocarditis in rats after administration of large amounts of testosterone propionate is related to the elevation of deoxycorticosterone in blood plasma but not to the direct effects of testosterone propionate on the myocardium.

Adrenalectomy↗
PubMedDate not supplied

Accumulation of carnitine in rat epididymis after injection of [3H]butyrobetaine in vivo: quantitative aspects, and the effects of androgens and antiandrogens.

After i.m. injection of [3H]butyrobetaine into intact and castrated rats, the specific activity of plasma carnitine remained nearly constant over 24--96 h and epididymal uptake of carnitine was constant per unit time up to 72 h. The uptake ratio of intact to castrated rats was high at 48, 72 and 96 h after injection. Administration of estradiol valerate over 20 days reduced carnitine uptake in epididymis. This reduction was dose-dependent when estrogen was administered i.m. at 0.33--10 microgram/day levels. A maximum reduction of 90% was obtained with the 10 microgram dose. A dose increase from 33 to 100 microgram/day caused no further reduction. Norspiroxenone (2--10 mg/day) and SK 7670 (1.5 and 7.5 mg/day) were less effective than estradiol valerate (10 microgram/day) in suppressing carnitine uptake in epididymis. Epididymal carnitine uptake in estradiol valerate treated rats (33 microgram/day for 20 days) increased in a time- and dose-dependent manner under testosterone propionate treatment (50, 250, 1250 microgram/day). Carnitine uptake increased to 80% of the nonsuppressed levels when testosterone propionate was adminsitered over a 6-day period at 1250 microgram/day. Dihydrotestosterone increased epididymal carnitine uptake to the same extent as testosterone propionate. delta4-androstene-3,17-dione and 5alpha-androstane-3alpha,17beta-diol (50 microgram/day) were less effective, stimulating uptake to only 15% and 40% respectively of the testosterone propionate (250 microgram/day) stimulated levels. Changes in epididymal carnitine uptake evoked by various experimental procedures were closely paralleled by weight changes in the ventral prostate. This response resemblance indicates a similarity between the androgen sensitivity of the prostate gland and that of the carnitine uptake system in epididymis. The dose-dependent effect of estrogen on the accumulation of epididymal carnitine, together with the marked responses induced in this system by manipulation of its androgen status, support a possible use for the system as an assay for androgen or antiandrogen potency in vivo.

Androgen Antagonists↗
PubMedDate not supplied

[Incomplete testicular feminisation syndrome by testosterone insensitivity (author's transl)].

Male pseudo-hermaphroditism by partial testosterone sensitivity, without steroido-genesis abnormality, without apparent 5 alpha reductase deficit - Empty complete scrotum and hypospadias surgically normalized. At 39, scrotal testis 32 X 15 mm right, 23 X 10 mm left. Infantile penis and prostata. Gynoid scapulo-pelvic proportions, adipo-muscular ratio and fat distribution. Bilateral gynecomastia. Caryotype 46 XY - 17 ks 26 mg. After intravenous 100 ng LH RH: plasma (pl) LH increased 105 to 285 ng/ml, pl testosterone 5 ng/ml unchanged, pl oestradiol 115 to 135 pg/ml. 48 h after intra muscular 300 mg testosterone propionate: pl testosterone increased, 13 to 39 ng/ml, androstenedione 1,5 to 3,04 ng/ml, dihydrotestosterone 0,85 to 1,45 ng/ml, OEstradiol 52 to 110 pg/ml. No effect of 29 g testosterone oenanthate in 2 years.

Adult↗
PubMed1987

Tamoxifen does not block the inhibitory effect of testosterone on FSH release in rats.

The aim of the present experiments was to analyze whether the inhibitory effect exerted by testosterone on FSH release might be mediated by the intracerebral transformation of the hormone into oestrogenic metabolites. Advantage has been taken of the availability of the potent antioestrogen tamoxifen. Two series of experiments have been performed. In the first one, adult male rats have been castrated and submitted, beginning immediately after surgery, to a 6-day treatment with testosterone propionate (2 mg/rat/day), tamoxifen (50 or 200 micrograms/rat/day) or testosterone propionate (2 mg/rat/day) plus tamoxifen (either 50 or 200 micrograms/rat/day). In the second experiment, adult male rats have been castrated and submitted to the same 6-day treatments, beginning 4 weeks following orchidectomy. In both experiments, the animals were killed 24 h after the last injection, and serum levels of FSH and LH have been measured by radioimmunoassays. The results have clearly shown that, in both experiments, the administration of testosterone results in a significant decrease of serum FSH and in a total suppression of LH release. The administration of tamoxifen, in either dose, does not modify the elevated serum FSH and LH levels present in the orchidectomized animals, and does not antagonize the inhibitory effect on FSH and LH secretion exerted by the concomitant treatment with testosterone propionate. It is concluded that testosterone inhibits FSH secretion in orchidectomized rats acting as such, and not following aromatization to oestrogens.

Animals↗
PubMed2004

Effects of testosterone and vitamin E on the antioxidant system in rabbit testis.

The aim of the study was to investigate the effects of testosterone propionate and vitamin E on the antioxidant system in the testis. Thirty-two male New Zealand White rabbits were randomly divided into four groups. The first group was used as control. The second group was injected with testosterone propionate, the third group vitamin E and the fourth group vitamin E and testosterone propionate combination. All treatments were carried out during 6 weeks and oxidative parameters were evaluated in homogenized testicular tissue. The levels of vitamin E and the activity of glutathione peroxidase were lower (P < 0.05) in the testosterone group than in controls. However, vitamin C and malondialdehyde levels were higher (P < 0.05) in this group than in controls. The levels of reduced glutathione, beta-carotene, vitamin C and E increased, but malondialdehyde levels decreased in the vitamin E group, when compared with controls (P < 0.05). Vitamin E and beta-carotene levels were significantly higher (P < 0.05) in the combination group than in testosterone group. However, MDA levels were lower (P < 0.05) in combination group than in the testosterone group. In conclusion, administration of testosterone propionate led to a significant elevation of oxidative stress. Vitamin E is quite an effective antioxidant which protects rabbit testis against lipid peroxidation, and, testosterone-induced lipid peroxidation could be improved by additional vitamin E treatment.

Androgens↗