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The relationship of the oestrogen and progestin receptors in the abnormal uterus of the adult anovulatory rat. Effects of neonatal treatment with testosterone propionate or clomiphene citrate.

The neonatal administration of testosterone propionate to Wistar rats resulted in anovulatory adults in persistent vaginal oestrus. Clomiphene citrate had a similar effect. In both groups of adults, hyperplasia of the uterine epithelium and occasional metaplasia was observed. The uterine nuclear and cytosol oestrogen and progestin receptors of these anovulatory rats were found to have affinities for their respective ligands similar to those of normal females. The nuclear oestrogen receptor comprised occupied and unoccupied components, as in normal females. The content of the nuclear oestrogen receptor was comparable with that of females in the late dioestrous or pro-oestrous phase. This content was higher in the clomiphene-treated group. Despite the relatively high nuclear oestrogen receptor content the content of progestin receptors, a putative index of the oestrogenic response, was lower in the treated rats than in normal adult females throughout the cycle. Administration of oestradiol to both treatment groups resulted in depletion of cytosol oestrogen receptor content 1 h later, which, however, was not reflected by an increase in the content of nuclear oestrogen receptors. There was no measurable increase in progesterone receptor content in treated rats after daily administration of oestrogen (5 microgram/rat) for 3 days. These changes in sex-hormone-receptor interactions involving an impairment of the normal oestrogenic response may be associated with the abnormal differentiation of the uterus in these sterile, anovulatory animals.

Animals↗

Influence of a transscrotal testosterone propionate administration on the serum level of selected hormones of the hypophyso-gonadal axis.

This study was designed to examine the effect of a percutaneous scrotal administration of testosterone propionate (TP) on selected blood variables, in order to identify a reliable anti-doping probe liable to disclose the illicit use of testosterone. Twelve healthy adult males gave their informed consent for the study. Each morning (8:30) and for 10 consecutive days (D), a placebo (D:1,2,3,...8,9,10) or a testosterone propionate (200mg TP on D:... 4,5,6,7...) scrotal patch was installed. On D2 or D3 (placebo-treated) or D7 (TP-treated), venous blood samples were collected at 5 min intervals from 9:00 until 13:00. Serum LH, FSH, 17alpha-hydroxyprogesterone (17HP), testosterone (T), estradiol (E2) and SHBG contents were analysed by immunoassays. The high sampling frequency revealed that TP was associated with the complete abolition of serum LH pulses. Although statistically significant, TP treatment was not related to explicit changes in serum FSH, E2, T/E2 and T/SHBG. TP-induced effects were most significant on serum LH, T and 17HP and were most clearly illustrated by a bi-dimensional distribution plot of serum values of the latter variables. The expression of a combination of the latter parameters could eventually serve to detect testosterone misusers.

17-alpha-Hydroxyprogesterone↗

The stimulatory effect of testosterone propionate and 17 beta-estradiol on 5'-methylthioadenosine phosphorylase activity in rat target tissues.

The effect of castration and subsequent administration of 17 beta-estradiol and testosterone propionate on 5'-methylthioadenosine phosphorylase activity in rat target tissues was studied. Castration 34 days earlier resulted in a 95% reduction in ventral prostate 5'-methylthioadenosine phosphorylase activity and 16 days earlier in a 67% reduction in uterine 5'-methylthioadenosine phorphorylase activity. Four days of testosterone propionate administration stimulated ventral prostate 5'-methylthioadenosine phosphorylase activity 32% above castrate levels, which represented more than 50% of the intact control levels. 17 beta-Estradiol on the other hand stimulated uterine 5'-methylthioadenosine phosphorylase activity 35% above castrate controls within 24 h and with 3 days of continuous hormone treatment to within 97% of the intact control levels. However, castration and subsequent 17 beta-estradiol administration did not affect 5'-methylthioadenosine phosphorylase activity in rat liver and lung. Both prostate and uterine 5'-methylthioadenosine phosphorylase were shown to metabolize 5'-methylthioadenosine to 5-methylthioribose through a 5'-methylthioribose 1-phosphate intermediate. The data suggest aht 5'-methylthioadenosine is not allowed to accumulate in rat target tissues even under conditions which are known to stimulate polyamine synthesis.

Animals↗

The effects of implanting testosterone propionate into the central nervous system on the sexual behaviour of adrenalectomised female rhesus monkeys.

Bilateral adrenalectomy rendered ovariectomised, oestrogen-treated female rhesus monkeys sexually unreceptive. Small unilateral implants of testosterone propionate (mean weight 140 mug) into the anterior hypothalamus/preoptic area restored receptivity in 7 out of 8 of these monkeys. Cholesterol implanted into the same area, or similar amounts of testosterone propionate implanted into the posterior hypothalamus/pretectal area (4 females) or cerebral cortex/dorsal thalamus (5 monkeys) had no consistent effect on behaviour. It therefore seems likely that androgens regulate sexual receptivity in female monkeys by acting on some part of the anterior hypothalamus. Thus, though the hormonal control of receptivity in female primates differs from non-primates, the site on which hormones act to regulate this behaviour may be similar in both.

Adrenal Glands↗

The effect of testosterone propionate supplement on testicular toxicity with thiamphenicol in male Sprague-Dawley rats.

Testosterone propionate (TP) was supplemented to male rats for assessment of its ameliorating effect on testicular toxicity with thiamphenicol (TAP). A total of 20 male Sprague-Dawley rats were treated orally with TAP at 200 mg/kg/day for up to 4 weeks. In addition, 5 male rats were allotted to the control group receiving vehicle only. Ten of the 20 treated rats had a Silastic capsule (containing about 80 mg of TP) implanted in the dorsal skin at Week 2 and assigned to the TAP-TP group, while the other 10 treated rats were in the TAP group. After Weeks 3 and 4, five of both treated groups were examined for weight and histology of the testis and accessory genital glands, and for staging analysis of the seminiferous tubules. The same parameters were also assessed in the control group after Week 4. Weights and morphology of the seminal vesicle and prostate recovered remarkably from the TAP toxicity after TP supplement. However, no ameliorating effects of TP were obtained for the testis in either weight, morphology, or staging analysis of the seminiferous tubules.

Animals↗

The development of unusual B-cell functions in the testosterone-propionate-treated chicken.

Chickens were treated with 4 mg of testosterone propionate on the twelfth day of embryonic life. Bursal remnants of testosterone-treated chickens were very small in size and had very few or no bursal follicles: the lymphoid tissue was replaced substantially by fibrosis. Testosterone-treated chickens formed almost exclusively IgM antibodies to sheep red blood cells and influenza virus, whereas no IgM or IgG response to Brucella abortus or Salmonella pullorum, and no IgG response to sheep red blood cells was demonstrable. Surgical removal of bursal remnants of testosterone-treated chickens at hatching did not significantly affect IgM response to sheep red blood cells. These B-cell functions of testosterone-treated chickens were not improved by addition of T cells, as shown by adoptive cell transfer experiments. Thus, there appears to be an unusual type B-cell development which is independent of the bursa of Fabricius.

Animals↗

Perturbation of fluid reabsorption in the efferent ducts of the rat by testosterone propionate, 17beta-oestradiol 3-benzoate, flutamide and tamoxifen.

The regulation by oestradiol and testosterone of fluid reabsorption in the efferent ducts of the rat was investigated by determining the effects of administering the hormones and their antagonists. Untreated rats were compared to animals treated for 7 days with testosterone propionate (1 mg d(-1)), oestradiol benzoate (400 microg d(-1)), flutamide (10 mg d(-1)) or tamoxifen (1 mg d(-1)). Two procedures were used to measure perturbation of transepithelial fluid fluxes in vivo. The first procedure used cannulation of the proximal epididymal duct and micropuncture of the rete testis to compare the rate at which fluid enters and leaves the efferent ducts. Oestradiol administration increased (p < 0.001) the volume of fluid entering the epididymal duct from the efferent ducts (i.e. reduced reabsorption) while flutamide and tamoxifen decreased (p < 0.05) the amount of fluid entering the epididymal duct (i.e. increased fluid reabsorption). Testosterone did not have a statistically significant effect, although it produced a small increase in fluid reabsorption. There was some perturbation of the concentration of electrolytes and the osmotic pressure of the fluid leaving the efferent ducts, but as these were not large, it is suggested that the treatments had little effect on the basic mechanisms of osmotic water transport via solute-solvent coupling. The second procedure used to test the effect of the steroids involved microperfusing individual efferent ducts, and the results were consistent with those of the first study. Oestradiol decreased fluid reabsorption by the efferent ducts (p < 0.05), and testosterone (p < 0.05, lowest perfusion rate only), flutamide (p < 0.001) and tamoxifen (p < 0.01) increased reabsorption. The similar responses to flutamide and testosterone administration suggest that flutamide acted as an androgenic agonist by elevating systemic and luminal androgen. It is concluded that fluid reabsorption in the efferent ducts is perturbed by oestrogens and androgens. Although their actions have not been completely resolved, it is proposed that they are involved in a chronic regulation, with androgens stimulating and oestrogens suppressing fluid reabsorption by the ducts.

Androgen Antagonists↗

Endocrinological and histological aspects of the process of polycystic ovary formation in the rat treated with testosterone propionate.

To elucidate the process underlying polycystic ovary (PCO) syndrome, we tried to produce experimental PCO by sterilizing rats with androgen and investigated the formation of PCO endocrinologically and histologically. Wistar-Imamichi strain female rats were given an injection of testosterone propionate 1.25 mg on 5 days of age. On 5, 10, 20, 40, 60, 80, 100, 130, 160, 200 days after the injection the ovaries were obtained. Ovarian wedge resection was also performed at 100 and 200 day-rats. Serum gonadotropins, prolactin and steroids were measured with RIA and compared with ovarian pathology. Serum prolactin was increased drastically 40 days after the injection and maintained at a constant level higher than control. Through wedge resection, the serum LH level returned to normal, but FSH slightly increased. Serum estradiol decreased more markedly than estrone did. The 40 day-ovaries showed polycystic features, lack of corpus luteum, hyperthecosis, luteinization of stroma, while no thickening of tunica albuginea. In conclusion, the rats treated with testosterone propionate had many endocrinological and histological aspects similar to those of human PCO syndrome.

Animals↗

Protection by testosterone propionate against the nephrotoxicity of 2-aminoanthraquinone in Fischer rats.

The role of gonadal hormones in the nephrotoxicity of the hepatocarcinogen 2-aminoanthraquinone (2-AAQ) was investigated. Intact and castrated four week old Fischer rats of both sexes and castrated female rats with subcutaneous implants of testosterone propionate pellets were fed 2% 2-AAQ in a Wayne meal diet. After 12 weeks of ad libitum feeding the animals were then given control diet. Based on survival, body, liver and kidney weights, and the histopathological evaluation of the kidneys, castrated female rats given testosterone propionate were afforded the greatest protective effect against the nephrotoxicity of 2-AAQ.

Amines↗

Effects of testosterone propionate on hindlimb-immobilized rats.

Forty albino male rats were randomly divided into 4 groups of 10. Group I served as the nonimmobilized control and received daily placebo injections of sesame oil. The rats in group II were castrated, their hindlimbs were immobilized using a plaster cast, and they received daily injections of sesame oil. The group III rats were also castrated and casted but received a daily injection of 5 mg testosterone propionate. The animals in group IV were not castrated but were casted and received daily testosterone propionate injections. The duration of each treatment was 15 days for each rat. The gastrocnemius, quadriceps, soleus, and cardiac muscles were weighed after treatment. O2 consumption capacity (QO2), citrate synthase activities, and percentages of water were measured in the gastrocnemius, quadriceps, and cardiac tissues. Along with the atrophy of muscle and reduction in body size, the immobilization significantly reduced the aerobic capacity of affected muscle groups and cardiac tissue. The greatest reductions in body weight, muscle size, heart size, and QO2 were seen in the castrated group that received only placebo injections of sesame oil. The anticatabolic effects of the anabolic steroid were evident in groups III and IV. The results indicate that hindlimb immobilization not only causes severe atrophy in those muscles immobilized but has an overall catabolic effect on the animal. Testosterone, or the lack of it, can significantly affect the amount of muscle atrophy.

Animals↗

[The effect of testosterone propionate, 5 alpha-dihydrotestosterone and 5 alpha-androstan-3 beta, 17 beta-diol on acid phosphatase activity in the prostate of castrated rats].

The acid phosphatase is studied in the prostate gland of rats. It is shown that 10 days after gonadectomy the activity of acid phosphatase lowered considerably. Administration of testosterone propionate or 5 alpha-dihydrotestosterone to castrated animals restored the enzyme activity whereas 5 alpha-androstan-3 beta,17-diol was not effective. Administration of testosterone propionate with one of its metabolites increased the activity of acid phosphatase in the prostate gland, however to a less extent than with the use of the hormone itself. The lowest activity is detected with the simultaneous application of three androgens.

Acid Phosphatase↗

Induction of skin and thyroid tumors in male rats by N-methyl-N-nitrosourea after sequential treatment with cyproterone acetate and testosterone propionate: effects of castration, rat strain and time of carcinogen injection.

The purpose of this study was to determine the carcinogenic effect in male rats of a single i.v. injection of N-methyl-N-nitrosourea (MNU) after sequential treatment with cyproterone acetate (for 21 days) and testosterone propionate (for 3 days). This treatment has previously been shown to induce carcinomas of the prostate and other male accessory sex glands. A wide spectrum of non-melanoma skin tumors was found in 38-48% of Wistar (Cpb:WU) rats given this sequential treatment, but only in 5% of rats that received only MNU. Castration long and, particularly, early after MNU markedly reduced this skin tumor response to a 10-13% incidence. The skin tumorigenic efficacy of MNU was dependent on the time between the start of the testosterone propionate treatment and carcinogen administration: MNU injection after 48-50 or 60-63 h induced skin tumors in 17-21% of Wistar rats, whereas injection after 72-74 h induced a 48% incidence. The Fischer F344 and Sprague-Dawley strains were not very sensitive to induction of skin tumors by this approach. Thyroid follicular cell tumors were also induced by MNU only after the hormonal pretreatment, and their induction was influenced by the time of MNU injection as well. The time of MNU injection and rat strain used did not significantly influence the induction of sebaceous-squamous neoplasms of the ear-duct/Zymbal's glands or other tumors. These data indicate that endogenous androgens are critically involved in the later stages of rat skin tumorigenesis and suggest that androgen-induced cell proliferation influences the initiation stage of this process and, possibly, of thyroid tumorigenesis.

Animals↗

HPLC method development for testosterone propionate and cipionate in oil-based injectables.

Two isocratic liquid chromatographic methods for the determination of testosterone propionate (TP) and cipionate (TC) in oil-based injectables using methyltestosterone and bolasterone as internal standards, respectively, have been developed and validated. Mobile phases 57% water:acetonitrile 43% (v:v) and 54% water:acetonitrile 46% (v:v) were used for TP and TC, respectively. For both methods, a bonded-silica Luna CN (250 mm x 4.6 mm i.d., 5 microm) (25 degrees C) column, a flow-rate 1 ml min(-1) and UV absorbance detection at 245 nm were used and two separations up to base line were achieved. Prior to HPLC analysis, sample preparation was required, including extraction of TP and TC from oil-based injectables using the surfactant sodium dodecyl sulphate.

Chromatography, High Pressure Liquid↗

Sexual behaviour in ovariectomized cows treated with oestradiol benzoate and testosterone propionate.

Sexual behaviour was not induced in ovariectomized cows by single doses of 100 or 250 micrograms oestradiol benzoate or by 3 injections of 50 micrograms oestradiol benzoate given at 12-h intervals. Treatment with 3 doses of 250 or 500 micrograms oestradiol benzoate at 12-h intervals produced plasma levels that were similar to those during pro-oestrus and oestrus in intact cows, and 11 of 12 treated animals showed oestrous behaviour. The higher dose resulted in a more pronounced response in 'mounting' and 'mounted' behaviour and a shorter interval to the onset of behavioural signs of oestrus. Oestrous behaviour was not observed in any ovariectomized cows treated with 1,2 or 20 mg testosterone propionate, doses that resulted in plasma levels comparable to those in intact pro-oestrous animals. Treatment with pharmacological doses of testosterone propionate resulted in transient mounting and interest in similarly treated females, but the results were inconsistent.

Animals↗

Active immunization of boars against gonadotropin releasing hormone. II. Effects on libido and response to testosterone propionate.

Of 20 sexually mature Duroc boars showing normal libido, 10 were actively immunized against gonadotropin releasing hormone (GnRH). After immunization against GnRH, boars showed minimal sexual interest in an estrous female, while untreated boars showed normal libido. Eight of the boars actively immunized against GnRH were randomly assigned to treatment (T) or control (C) groups. Boars in the T and C groups were given testosterone propionate or vehicle, respectively, on Days 0, 5, 10, and 15. Boars in both groups were observed for libido in the presence of an estrous female every 4 d for 28 d. Mean libido score for T boars increased gradually until all boars displayed maximum libido on Day 20, but libido returned to low levels on Day 28. In contrast, C boars remained sexually inactive throughout the study. The results of this study indicate that active immunization of sexually mature boars eliminates sexual behavior and that sexual behavior can be restored quickly by administering testosterone propionate.

Journal Article↗