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PubMed1979

Serum gonadotrophin levels in prepubertally castrated male sheep treated for long periods with propionated testosterone, dihydrotestosterone, 19-hydroxytestosterone or oestradiol.

At different times of the year, groups of wethers were treated with 20 mg testosterone, dihydrotestosterone or 19-hydroxytestosterone propionates/day or 2 mg oestradiol dipropionate/day, or the oil vehicle, for 6 weeks after a 2-week control period. LH and FSH values were determined by radioimmunoassay of serum samples collected at regular intervals. Oestradiol and dihydrotestosterone reduced LH and FSH concentrations whereas 19-hydroxytestosterone and testosterone had no effect.

Animals↗
PubMed1977

Changes in aggressive and sexual responsiveness of male golden hamsters after neonatal androgen administration.

On day 1 after birth, male golden hamsters received either 300 microng of an androgen (testosterone propionate, testosterone, dihydrotestosterone or androstenedione) in 0-03 ml arachis oil, or oil alone. As intact adults, their aggressiveness towards unreceptive females was measured. After this, all animals were castrated. At least 3 weeks after the operation all animals received oestradiol benzoate (10 microng) + progesterone (500 microng), after which their capacity to show patterns of female sexual behaviour towards a stud male was tested. Control hamsters which had received oil as neonates showed less aggression than the females with which they interacted; these controls also readily assumed lordosis after castration and priming with ovarian steroids. Conversely, animals which had received testosterone propionate or androstenedione neonatally were as aggressive as the female hamsters, and showed a markedly decreased ability to display lordotic behaviour after castration. The behaviour of male hamsters which received testosterone or dihydrotestosterone was unaffected. Thus, at the level of treatment used, increased aggressiveness appeared to co-vary with a decreased capacity to show female sexual behaviour patterns. However, within each treatment there was little evidence of such a relationship at the level of the individual animal.

Aggression↗
PubMed1995

Treatment of constitutional delayed puberty with a combination of testosterone esters.

Thirteen boys who had constitutional delayed puberty (CDP) were treated with a combination of short- and long-acting testosterone esters (testosterone propionate, testosterone phenylpropionate, testosterone isocaproate). Mean age at the onset of treatment was 14.9 +/- 0.6 years and bone age delay was -2.7 +/- 0.9 years. An intramuscular dose of 200 mg testosterone was administered 4 times at 3-week intervals and the treated CDP boys were followed for 2 years. All boys with CDP entered puberty after the last dose (testicular volume > or = 4 ml) and growth rate increased from 4.5 +/- 0.5 cm/year pretreatment to 8.4 +/- 1.6 cm/year posttreatment after the 2-year follow-up period. Height for bone age SD score did not alter significantly from a mean of -1.1 pretreatment to -1.3 posttreatment as well as predicted height pretreatment (173.5 +/- 6.6 cm) and posttreatment (173.3 +/- 4.9 cm). A combination of testosterone esters in a given dose and schedule is a safe and effective treatment for prepubertal boys with CDP.

Adolescent↗
PubMedDate not supplied

Treatment of constitutional delayed puberty with a combination of testosterone esters.

Thirteen boys with constitutional delayed puberty (CDP) were treated with a combination of short and long-acting testosterone esters (testosterone propionate, testosterone phenylpropionate, testosterone isocaproate). Mean age at the onset of treatment was 14.9 +/- 0.6 years and bone age delay was -2.7 +/- 0.9 years. The dose of testosterone used was 200 mg intramuscularly four times at three week intervals, and the treated CDP boys were followed for two years. All the boys with CDP entered puberty after the last dose (testicular volume > or = 4 ml), and growth rate increased from 4.5 +/- 0.5 cm/year, pretreatment, to 8.4 +/- 1.6 cm/year, posttreatment, at the two year follow-up. Height for bone age SD score did not change significantly from a mean of -1.1 before treatment to -1.3 after treatment, nor did predicted height before treatment (173.5 +/- 6.6 cm) and after treatment (173.3 +/- 4.9 cm). Combination of testosterone esters in a given dose and schedule is a safe and effective treatment for prepubertal boys with constitutional delayed puberty.

Adolescent↗
PubMed1999

Identification of testosterone and testosterone esters in human hair.

In 1974, steroids were added to the list of doping agents banned by the International Olympic Committee because of their effects on the performance of the athletes. Testosterone and its esters promote the development of secondary male sexual characteristics and accelerate muscle growth. The mandatory test to detect testosterone abuse is to measure the ratio of testosterone to epitestosterone in the urine. However, because athletes can adjust their dosage to stay within the range permitted, there is a risk of test evasion. Therefore, we developed two original procedures to determine testosterone and its esters in human hair. First, testosterone was investigated in hair obtained from 26 control subjects. After decontamination with dichloromethane, 100 mg of hair was incubated in 1 M NaOH in the presence of 1 ng of testosterone-d3. After neutralization, the extract was purified using solid-phase extraction with Isolute C18 columns followed by liquid-liquid extraction with pentane. After silylation, testosterone was analyzed by gas chromatography-mass spectrometry. Concentrations were in the range 1.2 to 11.4 pg/mg with a mean value of 3.8 pg/mg. To distinguish exogenous abuse from endogenous levels, the incorporation of testosterone esters into hair was investigated. Preparation involved methanolic incubation to avoid the cleavage of the esters. In a panel of eight esters, it was possible to identify testosterone propionate, testosterone enanthate, and testosterone decanoate in the hair of two bodybuilders and one weight lifter. This new technology may find useful applications in anabolic abuse control.

Adolescent↗
PubMed1977

The effect of various treatments on the size of sebaceous glands of hairless mice and hairless hamsters.

The effect of castration on the size of sebaceous glands of male hairless mice and male hairless hamsters was studied over a period of 4 weeks. Statistically significant decreases in the size of sebaceous glands were observed. The effects of intracutaneous injections of micronized crystalline suspensions of testosterone, testosterone propionate, testosterone phenylpropionate, testosterone decanoate and nandrolone phenylpropionate on the sebaceous glands of castrated hairless mice, castrated hairless hamsters and intact female hairless hamsters were studied over a period of one week. Highly significant increases in sebaceous gland volume were observed 6-7 days after treatment. The effects of subcutaneous and intracutaneous injections of micronized crystalline suspensions of testosterone on the sebaceous glands of intact male and female hairless hamsters were examined at sites local and distal to the injection. Increases in sebaceous gland volume were limited to local sites in the male but increases were observed locally and distally in the female. There was no difference between subcutaneous and intracutaneous injections.

Animals↗
PubMed1981

Subdermal implants of different steroidal compounds for treatment of endocrinological disorders.

Various types of steroid-containing implants were used in the treatment of benign prostatic hypertrophy, congestive prostatitis, and hypogonadism. 2 Silastic capsules, each containing 22-23 mg of ethinyl estradiol, were inserted subcutaneously in 5 men with benign prostatic hypertrophy. A decline in testosterone levels to less than 1 ng/ml was attained within 6 months following insertion. 6-8 Silastic capsules containing 21-23 mg each of testosterone were implanted in 15 men: 2 castrates and 13 hypogonadals. Testosterone levels increased initially, reaching the highest level at 3 months. Thereafter, the testosterone concentrations declined but remained slightly above pretreatment levels at 9 months. In a group of 9 subjects, 7 men with hypogonadism and 2 women with hypernephroma were treated with 2 rods, each containing approximately 200 mg testosterone propionate. Testosterone concentrations showed initial rises but did not remain elevated. 12 male subjects, 6 with congestive prostatis and 6 with benign prostatic hypertrophy, were treated with a combination of 3 levonorgestrel rods and 3 estrone rods. Each rod contained 40 mg of steroid. This regimen had a therapeutic effect but was only partially successful in inhibiting spermatogenesis.

Adult↗
PubMed2002

Gender-related differences in mouse hepatic ethanol metabolism.

The effect of an acute oral load of 2 g ethanol/kg body weight was studied in a group of male and female 10-wk-old C3H/HeNCrj (C3H/He) mice to investigate gender change throughout differences of the hepatic ethanol metabolism of mice. The following parameters were measured in the serum from 0 h to 3 h after the start of the experiment: ethanol, acetaldehyde, and acetate. Their concentrations in the serum in female mice tended to show lower levels than in male mice. In female mice, the concentration of ethanol at 1 h and the concentration of acetate at 1 h, 2 h, and 3 h after ethanol administration showed significantly lower levels than in male mice. Ten-week-old male and female C3H/He mice were subcutaneously injected 50 microg/kg body weight beta-estradiol and 1.45 mmol/kg body weight testosterone propionate (testosterone) in olive oil, respectively, and changes in the activity of enzymes related to the hepatic ethanol metabolism of mice were examined at 24 h after the administration of sex hormones. The activity of the cytosolic alcohol dehydrogenase (ADH) and microsomal aniline hydroxylase (ANH) and the low Km, high Km and total aldehyde dehydrogenase (AlDH) activities in the mitochondrial, the cytosolic, and the microsomal fraction of the liver were higher. Moreover, the density of the band of CYP2E1 in the microsome in female mice was stronger than in male mice, and in the microsomal fraction of the liver, the total content of cytochrome P-450 (CYP) and ethoxyresorufin O-dealkylase (EROD) activity in male mice showed significantly higher values than in female mice. The density of the band of CYP2E1 and the three activities of AlDH in the hepatic mitochondrial fraction of male mice increased significantly under treatment with beta-estradiol. The three activities of AlDH of the cytosolic fraction of the liver in female mice significantly decreased under treatment with testosterone. The present findings suggested that in C3H/He mice livers, the rate of ethanol metabolism is faster in females than in males, and the enzymes related to ethanol metabolism are controlled by testosterone or beta-estradiol. It is suggested that ethanol and its metabolite disappear faster from the serum of female mice than from the serum of male mice because the activities of hepatic enzymes related to ethanol metabolism are higher in female mice than in male mice. C3H/He mice, hepatic ethanol metabolism, gender different, ADH, AlDH

Acetaldehyde↗
PubMed1986

Maturational and hormonal influences on Sertoli cell function.

The maturation of Sertoli cell function was studied by observing properties of cells obtained from 15-, 25-, and 35-day-old rats after 3 days in culture gamma-Glutamyl transpeptidase activity, expressed per mg DNA or per mg protein, and total and soluble protein to DNA ratios increased with age. In contrast, lactate dehydrogenase activity was unchanged between 15 and 35 days of age. Secreted protein to DNA ratios and the secretion of lactate, androgen-binding protein (ABP), and transferrin per mg DNA also increased with age. Two-dimensional electrophoresis maps of [35S]methionine-labeled secretory proteins indicated the appearance of two specific bands [mol wt, 66,000; pI 6.0-6.8 (band 1); mol wt, 56,000; pI 5.3-6.0 (band 2)] between 15 and 35 days of age. The hormone dependence of these parameters was studied in Sertoli cells isolated from rats hypophysectomized at 20 days of age and subsequently treated with oil, testosterone propionate, or testosterone propionate plus FSH for 15-21 days. Hypophysectomy decreased total, soluble, and secreted protein to DNA ratios; hormone treatment in vivo increased these ratios compared to oil treatment. gamma-Glutamyl transpeptidase activity was significantly decreased by hypophysectomy and increased, compared to oil treatment, by hormone treatment. In contrast, lactate dehydrogenase activity per mg DNA was also decreased by hypophysectomy, but was unaffected by hormone treatment. [35S]Methionine incorporation into secreted protein and secretion of ABP and lactate per mg DNA were all decreased by hypophysectomy, whereas transferrin secretion per mg DNA was unaffected. While the hormone treatments increased ABP secretion, they had no effect on lactate or transferrin secretion, expressed per mg DNA. The [35S]methionine-labeled secretory proteins (bands 1 and 2) were not visible in two-dimensional electrophoresis maps after hypophysectomy of the donor animals. Treatment with testosterone propionate or testosterone propionate plus FSH in vivo resulted in the appearance of the acidic components of band 2. These data demonstrate that changes reflecting in vivo maturational patterns and hormonal influences on Sertoli cell function persist, at least in a relative sense, after 3 days in culture. Although the majority of [35S]methionine-labeled Sertoli cell cellular and secretory proteins were present under all conditions, maturation- and hormone-dependent changes in a number of specific functions were demonstrated.

Animals↗
PubMed2000

Skin permeation of testosterone and its ester derivatives in rats.

To establish the optimum conditions for improving the transdermal delivery of testosterone, we studied the relationship between the lipophilicity of testosterone ester derivatives and the rat skin permeation rate of testosterone. We performed a rat skin permeation study of testosterone and its commercially available ester derivatives, testosterone hemisuccinate, testosterone propionate and testosterone-17beta-cypionate, using an ethanol/water co-solvent system. The aqueous solubility and rat skin permeation rate of each drug, saturated in various compositions of an ethanol/water system, was determined at 37 degrees C. The aqueous solubility of testosterone and its ester derivatives increased exponentially as the volume fraction of ethanol increased up to 100% (v/v). The stability of testosterone propionate in both the skin homogenate and the extract was investigated to observe the enzymatic degradation during the skin permeation process. Testosterone propionate was found to be stable in the isotonic buffer solution and in the epidermis-side extract for 10h at 37 degrees C. However, in the skin homogenate and the dermis-side extract testosterone propionate rapidly degraded producing testosterone, implying that testosterone propionate rapidly degraded to testosterone during the skin permeation process. The steady-state permeation rates of testosterone in the ethanol/water systems increased exponentially as the volume fraction of ethanol increased, reaching the maximum value (2.69+/-0.69 microg cm(-2)h(-1)) at 70% (v/v) ethanol in water, and then decreasing with further increases in the ethanol volume fraction. However, in the skin permeation study with testosterone esters saturated in 70% (v/v) ethanol in water system, testosterone esters were hardly detected in the receptor solution, probably due to the rapid degradation to testosterone during the skin permeation process. Moreover, a parabolic relationship was observed between the permeation rate of testosterone and the log P values of ester derivatives. Maximum flux was achieved at a log P value of around 3 which corresponded to that of testosterone (log P = 3.4). The results showed that the skin permeation rate of testosterone and its ester derivatives was maximized when these compounds were saturated in a 70% ethanolic solution. It was also found that a log P value of around 3 is suitable for the skin permeation of testosterone related compounds.

Animals↗
PubMed1983

Plasma testosterone levels in adult and neonatal female rats bearing testosterone propionate-filled silicone elastomer capsules for varying periods of time.

Testosterone propionate (TP) was administered, by means of subcutaneous implanted silicone elastomer capsules, into adult and neonatal (aged 3 days) female rats. In the adult rats a dose-dependent increase in plasma testosterone was measured for capsules of three different sizes (5, 10 and 20 mm crystal length). Testosterone levels reached a peak 4-8 h after insertion (5 mm, 24.6 +/- 1.4 (S.E.M.) nmol/l; 10 mm, 34.0 +/- 3.8; 20 mm, 44.4 +/- 3.1) and returned to control levels within 4 h after removal: the calculated half-life of testosterone was 1 h for all sizes of capsule. In neonates, a capsule of 2.5 mm crystal length was removed after 4 h subcutaneous implantation (at day 3 of age) and produced peak testosterone levels of 126.2 +/- 11.8 nmol/l: the calculated half-life was 8.6 h which compared with a half-life of 48 h after a subcutaneous injection of 312 mumol TP (in 0.05 ml arachis oil) which produced peak levels of testosterone in 4-8 h of 84.6 +/- 11.8 nmol/l. Chronic implants of TP-filled capsules (2.5 mm crystal length) at 3 days of age and left in situ for 15 weeks gave a half-life of 69 h. Removable silicone elastomer capsules were found to be a versatile vehicle for the administration of TP to rats of all ages where precise hormone treatment for a known period or prolonged administration is required. The duration and magnitude of plasma hormone levels should be established by assay in an in-vivo situation.

Age Factors↗