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Crowding pregnant mice affects attack and threat behavior of male offspring.

Attack and threat behavior of adult male offspring of female mice crowded during the final third of pregnancy was investigated. In 5-min test pairings with an anosmic "standard opponent" which had 50 microliter of male mouse urine applied to its fur, the prenatally stressed group of males showed significantly less attack behavior; attack latency was longer and number of attacks, bites, amount of time spent attacking, and composite aggression scores were all lower, compared with the control group. Similarly, less threat behavior was observed in offspring from crowded dams; there were lower frequencies of tail rattles, rough grooms, and upright threats. Additionally, proportionally fewer males in the prenatally stressed group attacked or displayed threats. A second experiment was designed to investigate the effects of exogenous androgen on the aggressiveness of males from crowded mice: testosterone propionate administration (500 micrograms/animal/day, for 5 days prior to testing) abolished differences both in the proportion of males from crowded mice that fought and also apparently abolished differences in intensities of attack and threat behavior between groups. However, trends toward reduced aggression in prenatally crowded males remained. More detailed analysis of these responses, based only on animals that displayed aggression, revealed significantly reduced intensity of aggression in offspring from females crowded during pregnancy, indicating that testosterone propionate therapy did not completely restore this behavior. In order to reduce postnatal effects due to possible differences in mothering, all offspring were fostered to untreated mothers at birth. The results are discussed in terms of in utero exposure of male fetuses of crowded dams to stress-liberated adrenal steroids of maternal origin, and the possible consequences for the endocrine integrity of these offspring.

Aggression↗

[3H]dexamethasone binding activity in liver microsomes is modulated differently by 17 alpha-alkylated androgens and testosterone in vivo.

Rat liver microsomes contain a single class of steroid binding sites, capable of binding various glucocorticoids and progesterone. In a previous article, we have described the in vitro interaction of several androgens with this binding site. Unlike natural androgens, the 17 alpha-alkyl derivatives stanozolol and danazol were capable of interacting with this binding site through a negative allosteric pattern. Now, the effects these steroids exert on the microsomal [3H]dexamethasone binding site have been studied in vivo. The administration of a single dose of stanozolol to rats provoked a significant reduction in the microsomal [3H]dexamethasone binding capacity. This effect was maximal two hr after stanozolol administration and persisted for six hr. The restoration of the [3H]dexamethasone binding level after stanozolol administration was dependent on protein synthesis, since it was blocked by the concomitant administration of cycloheximide. None of the other androgens tested (danazol, methyltestosterone, fluoxymesterone, and testosterone propionate) was capable of provoking a similar effect when administered 2 or 24 hr prior to sacrifice. In rats treated for seven days with a daily dose of diverse androgens and sacrificed 24 hr after the last treatment, none of the 17 alpha-alkyl androgens assayed provoked significant changes in the microsomal [3H]dexamethasone binding level, although stanozolol, danazol, and methyltestosterone provoked a significant increase in glucocorticoid receptor concentration. In contrast, the administration of testosterone propionate provoked a 50% reduction in the [3H]dexamethasone binding level without causing changes in the glucocorticoid receptor concentration. These results provide new evidence on the existence of different effects on the liver of 17 alpha-alkyl androgens, compared to the effects produced by natural androgens.

Anabolic Agents↗

Androgens, behaviour and fertility control in feral stallions.

This field study of feral stallions in Montana and Idaho examines and correlates the seasonal pattern of plasma androgens and specific sociosexual behaviour and reports the effect of a long-acting androgenic steroid on this behaviour and on fertility. Plasma testosterone was measured by competitive protein binding assay in samples obtained by jugular venepuncture from captured animals. In samples taken from 34 sexually mature stallions in 6 different months during the year, a definite seasonal pattern in testosterone was present, with a peak in May (3.04 +/- 0.63 ng/ml) and a nadir in December (1.55 +/- 0.34 ng/ml). Values were less than 2.0 ng/ml in non-breeding months and greater than 2.4 ng/ml in breeding months. Behavioural endpoints measured were (1) stallion scent marking in response to elimination by mares (elimination marking), (2) mounting and (3) copulation. The frequencies of each of these endpoints followed closely the seasonal pattern seen for plasma androgens. In the fertility study microcapsulated testosterone propionate (microTP) was administered i.m. to 10 harem stud stallions 3 months before the 1980 breeding season. In these stallions and in 10 control harem studs, the above behavioural endpoints were examined in the 1980 and 1981 breeding seasons, and foal counts were made in 1981. There were no direct inhibitory or stimulatory effects of microTP treatment on any of the behavioural endpoints in either year. In 1981 foals were produced in 87.5% of the control bands and 28.4% of the microTP-treated bands. These results indicate that microencapsulated testosterone propionate can provide effective fertility control in feral horses without causing significant alterations in sociosexual behaviour.

Animals↗

[The effect of synthetic derivatives of testosterone on the activity of acid proteinases, DNA-ase and RNA-ase in the liver and serum of female rats].

A study was made of the effect of a 30-day administration of various doses of testosterone-propionate and methyltestosterone to intact female rats given a ration rich in protein on the activity of acid DNA-ase, RNA-ase and proteinases in the liver and the blood serum. The ration itself, rich in proteins, increased the activity of acid RNA in the liver of rats and gave a significant seasonal variations in the activity of RNA-ase and proteinases. Administration of the same doses (1 mg daily) of testosterone-propionate or methyltestosterone produced a different effect on the nuclease metabolism. In the first case there was observed a reduction of the RNA-ase activity, and in the second--of the DNA-ase. Possibly this partially explained a different extent of anabolic properties of these two androgens. An increase in the dose of methyltestosterone to 5 mg, on the contrary, produced activation of RNA-ase in the liver and the blood serum, which could promote the manifestation of catabolic properties.

Animals↗

Influence of neonatal androgenization on the response of alpha 2u-globulin to testosterone and dexamethasone in the rat.

The influence of neonatal androgens on the response of alpha 2u-globulin to testosterone propionate or dexamethasone in adult rats has been investigated. It has been demonstrated previously that contact with androgens during the perinatal period results in higher unstimulated levels of alpha 2u-globulin in the serum of adult rats and in higher levels of this protein when the animals are stimulated either with androgens or glucocorticoids. As shown here, however, non-androgenized animals reached comparable serum levels to their neonatally androgenized litter-mates only during prolonged stimulation with testosterone propionate. Previous exposure to androgens during adulthood did not result in comparable differences in levels of alpha 2u-globulin in non-stimulated or stimulated rats. The residual sex difference in the stimulated levels observed in neonatally gonadectomized and oil-treated animals suggested that the sensitive period for this imprinting effect extends into the prenatal period.

Animals↗

[Effect of kidney tonifying herbs on morphological changes of adrenal cortex in androgen-sterilized rats].

Young rats of 9-day old with testosterone propionate subcutaneously injected were used as an androgen sterilized rats (ASR) model. On 80th day, herbal extract of tonifying the Kidney was fed for 14 days, all animals were sacrificed by cardiac perfusion method on 100 days of ages. Morphological studies with light and electron microscope, immunohistochemical studies with argyrophilic nucleolar organiser region (AgNOR) and proliferating cell nucleolar antigen (PCNA) were used for observations on the morphological change of adrenal cortex. In control group (treated with testosterone propionate only) the reticular zone of the adrenal cortex extented widely in which cellular fatty drops, AgNOR and PCNA increased apparently. In animal treated with herbs, the width of the reticular zone, the numbers of AgNOR and PCNA reduced significantly to normal levels (P < 0.01, P < 0.01, P < 0.01) and numbers of fatty drops also decreased. It suggests that during inducing ovulation in ASR tonifying Kidney herbs simultaneously regulated the adrenal function besides the chief function on pituitary-ovary regulation.

Adrenal Cortex↗

Sex steroids as a cause of adenocarcinoma of the dorsal prostate in Nb rats, and their influence on the growth of transplants.

The development of adenocarcinoma of the dorsal prostate of Nb rats following prolonged treatment with pellets of testosterone propionate alone or with esterone allowed the establishment of transplantable tumor models. Whereas most transplants were autonomous and not influenced by hormones, one estrogen dependent tumor was studied in detail. This tumor would only grow in estrogenised hosts, cells remaining dormant in normal animals. Removal of estrogen from animals with growing tumors led to tumor regression but with progression and eventual regrowth of tumors which were autonomous. Replacement with lower doses of estrogen reduced the extent of regression and prevented autonomous change. When a regressed estrogen dependent tumor was exposed to prolonged treatment with testosterone propionate pellets, the eventual regrowth was found to be androgen dependent and would not grow in estrogenised animals. Progression could apparently be directed by this procedure from estrogen to androgen dependency.

Adenocarcinoma↗

Serum prolactin and the suppression of lactation.

Bromocriptine (2 bromo-alpha-ergocryptine), stilboestrol, clomiphene citrate, testosterone propionate and a placebo were given to 75 postpartum women for the suppression of puerperal lactation. An additional 15 women who breast-fed their babies served as a control group. Blood samples were taken for the determination of serum prolactin levels by a specific homologous double antibody radioimmunoassay. Concurrently, the clinical effectiveness of the various treatments was assessed. High levels of prolactin were found at the time of delivery. Bromocriptine effectively reduced serum prolactin and prevented lactation; stilboestrol increased serum prolactin and partially suppressed lactation; clomiphene citrate and testosterone propionate both lowered serum prolactin levels and partially suppressed lactation. The placebo showed almost no effect on serum prolactin. It appeared that bromocriptine was the drug of choice in the suppression of puerperal lactation.

Bromocriptine↗

Alteration of prolactin control in adult rats treated neonatally with sex steroids.

Androgenized, oestrogenized and control female and male rats were used to establish possible differences in the alteration of the prolactin control system. Neonatal treatment involved administration of oestradiol benzoate or testosterone propionate (TP) on days 1 and 5 to the males and on day 5 to the females. Oil-treated animals were used as controls. Plasma prolactin levels were measured in these animals during adulthood (a) before gonadectomy, performed on day 80, and 27 days after gonadectomy and (b) on the 2 days (at 10.00 and 17.00 h) after administration of a single dose of TP to gonadectomized animals. Oestrogenized rats had the highest plasma prolactin concentrations just before and after gonadectomy. Testosterone propionate increased plasma prolactin levels in all groups. This response was more notable in the female than in the male groups, and was highest in the oestrogenized animals. Temporal rhythms of the prolactin response to TP were daily, perhaps circadian, with increased levels in the afternoon compared with those in the morning. This pattern was not present in oestrogenized females and androgenized males. Results suggest (a) that oestrogens and androgens given neonatally differ in their ability to alter the prolactin control system, and (b) that females seem to be more sensitive than males to changes in hypothalamic differentiation induced by neonatal steroid treatment.

Animals↗

Neurosteroids regulate mouse aggression induced by anabolic androgenic steroids.

Anabolic androgenic steroid abuse triggers impulsive aggression, anxiety, and depression, which suggests a dysfunction of GABAergic neurotransmission. Socially isolated female mice that have received testosterone propionate (1.45 micromol/kg) treatment for 3 weeks during social isolation express aggression, neurosteroid downregulation, and changes in the cortical mRNA expression of several gamma-aminobutyric acid type A receptor subunits (alpha1, alpha2, gamma2 are decreased by 30-40%, and alpha4 and alpha5 are increased by 50%). Administration of allopregnanolone or the potent selective brain steroidogenic stimulant S-norfluoxetine, in doses (1.8-3.6 micromol/kg) that fail to inhibit 5-hydroxytryptamine reuptake, normalizes olfactory bulb neurosteroid level downregulation and abolishes aggression. This work underscores the role of neurosteroids in the regulation of aggression elicited by testosterone propionate in socially isolated female mice.

Aggression↗

[An experimental study of the inhibition of tamoxifen on rat model of benign prostatic hyperplasia].

OBJECTIVES: To study the inhibitory mechanism of tamoxifen on benign prostatic hyperplasia. METHODS: The Wistar male adult rats were injected into muscle with testosterone propionate 4-6 mg/kg, simultaneously were irrigated into stomach with tamoxifen citrate 0.21 mg/kg. The partly rats of each group were decapitated at 7, 15 and 30 days, then their index numbers of prostate were calculated, and the structural changes of the prostatic histocyte were observed in the light microscopy and scan electronic microscopy. RESULTS: At the 7th, 15th, and 30th day, the index numbers of prostate of those rats which had been injected only with testosterone propionate were higher than that of the control group and the irrigating group(P < 0.05). The hyperplasia of the prostatic epithelial cells and the ground substance of those rats, which had been irrigated with tamoxifen citrate, had not happened in light microscopy and the scan electronic microscopy. CONCLUSIONS: Tamoxifen could block the effect of the estrogen, which could suppress the prostatic hyperplasia. This study could provide the experimental evidences for using Tamoxifen to treat the human benign prostatic hyperplasia.

Animals↗

Effects of anabolic-androgenic steroids on hair waves in castrated mice.

The effects of nandrolone phenylpropionate and decanoate, androstanolone and testosterone propionate, in daily doses from 3 to 100 micrograms during a month, on the diffuse hair wave seen after gonadectomy, were studied in male C 57 mice. The androgenic effects upon anterior prostate weight and the anabolic effects upon levator ani muscle and submaxillary gland weight, were also evaluated. The four steroid compounds used in these experiments had a strong inhibitory effect upon the hair growth waves which was stronger in the anabolic steroids than with testosterone propionate.

Anabolic Agents↗

Modulation of the cytosolic androgen receptor in striated muscle by sex steroids.

We studied the influence of orchiectomy (GDX) and steroid administration on the level of cytosolic androgen receptor in rat levator ani muscle and rat skeletal muscles (tibialis anterior and extensor digitorum longus). Androgen receptor binding to muscle cytosol was measured using [3H]methyltrienolone (R1881) as ligand, a 100-fold molar excess of unlabeled R1881 to assess nonspecific binding, and a 500-fold molar excess of triamcinolone acetonide to prevent binding to glucocorticoid and progestin receptors. Bound and free ligand were separated by column chromatography with Sephadex G-75. In levator ani muscles from intact animals (controls), maximum R1881 binding (Bmax), determined by Scatchard analysis, was 2.5 fmol/mg protein (Kd = 0.68 nM). Thirty days after GDX, Bmax increased to 500% of the control value, with no significant change in Kd (0.96 nM). Using saturating levels of R1881, Bmax was increased to 280% of the control value 12 h post-GDX, 600% at 14 days, 478% at 30 days, and 133% at 44 days. The increase in receptor binding was blocked by cycloheximide. Administration of Silastic capsules containing testosterone propionate 30 days post-GDX resulted in R1881 binding at the control level at 44 days. Surprisingly, administration of 17 beta-estradiol (E2) 30 days post-GDX resulted in increased (480%) R1881 binding. Thus, E2 may cause induction of the cytosolic androgen receptor in levator ani muscle from GDX rats; alternatively, the rate of receptor degradation may be altered. R1881 binding by skeletal muscle cytosol was increased 139% at 12 h, 212% on day 14, 220% on day 30, and 158% on day 44 with respect to the control value. Administration of testosterone propionate at 30 days caused R1881 binding to return to the control value by day 44, whereas E2 was without influence. The differences in response of levator ani and skeletal muscle receptors may account for the differential effects of sex steroids on these muscle types.

Animals↗

Concentrations of putrescine and polyamines and their enzymic synthesis during androgen-induced prostatic growth.

1. Castration of adult rats resulted in marked decreases in the amounts of putrescine, spermidine and spermine in the ventral prostate gland. Spermidine concentrations decline rapidly over the first 11 days after androgen withdrawal, reaching a value of only 12% of normal controls. Spermine concentrations diminish more slowly, reaching 24% of normal within 11 days. The spermidine/spermine molar ratio falls from 0.9 to 0.46 under these conditions. Putrescine concentrations decrease by 70% at 7 days after castration and then remain constant for some days. 2. After daily injections of testosterone propionate to rats castrated 7 days previously, prostatic spermidine and putrescine concentrations increase significantly within 24h; normal or even greater values are observed within 8 and 4 days respectively. In contrast, the spermine concentration does not increase until 5 days after commencement of androgen treatment. 3. The activities of two enzymes involved in polyamine biosynthesis (ornithine decarboxylase and a putrescine-activated S-adenosyl-l-methionine decarboxylase system) were greatly decreased soon after castration: after 7 days the respective values were 15% of normal for ornithine decarboxylase and 7% of normal for putrescine-dependent decarboxylation of S-adenosyl-l-methionine. Injection of testosterone propionate into animals castrated 7 days previously induced a rapid increase in both enzymic activities: ornithine decarboxylase was doubled in 6h, and increased three- to four-fold within 48h, whereas the putrescine-dependent decarboxylation of S-adenosyl-l-methionine doubled in 3h and increased tenfold within 48h of commencement of daily androgen treatments. 4. The activity of these enzyme systems was very low in the ventral prostates of hypophysectomized rats and was increased by administration of testosterone in a manner similar to that found in castrated rats. 5. Alterations in the activity of two ventral-prostate enzymes involved in ornithine production (arginase) and utilization (ornithine-2-oxoglutarate transaminase) that result from changes in the androgenic status of rats are described. 6. The findings presented suggest that the activities of ornithine decarboxylase and the putrescine-dependent S-adenosyl-l-methionine decarboxylase system, rather than ornithine concentrations, are rate-limiting for the formation of putrescine and polyamines in rat ventral prostate. 7. The relation of polyamines to androgen-induced prostatic growth is discussed with particular reference to the biosynthesis of proteins and nucleic acids.

Amines↗

In vitro and in vivo effects of 17beta-trenbolone: a feedlot effluent contaminant.

Concern has arisen regarding the presence and persistence of trenbolone in the environment. Trenbolone acetate is an anabolic steroid used to promote growth in beef cattle. It is hydrolyzed to the active compound, 17beta-trenbolone (TB), which is also one of the metabolites excreted by cattle. Reproductive alterations have been reported in fish living in waters receiving cattle feedlot effluent, and in vitro androgenic activity displayed by feedlot effluent samples has been related to these effects. In the current study, the androgenic potency of TB was examined both in vitro and in short-term in vivo assays. TB was a high affinity ligand for the androgen receptor (AR), with an IC(50) of about 4 nM in rat ventral prostate cytosol and about 33 nM in cells transfected with the human AR when competed with 1 nM [3H]R1881. TB induced AR-dependent gene expression in MDA-kb2 cells with a potency equal to or greater than dihydrotestosterone. In immunocytochemistry experiments with the human AR, concentrations as low as 1 pM significantly induced androgen-dependent translocation of the AR into the cell nucleus. TB also displayed antiglucocorticoid activity in vitro, inhibiting dexamethasone-induced transcriptional activity, and reduced adrenal gland size in vivo. In the Hershberger assay (in vivo), TB was as potent as testosterone propionate in tissues that lack 5alpha-reductase but less effective at increasing weight of tissues with this enzyme. Such tissue specificity was anticipated because other C-19 norsteroidal androgens display a similar profile in this assay. Subcutaneous TB treatment was about 50- to 100-fold more effective in stimulating growth of androgen-dependent tissues than was oral treatment. In our in utero screening assay, maternal TB administration increased AGD and attenuated the display of nipples in female offspring in a dose-related manner, similar to the published effects of testosterone propionate. Previous studies have documented that these types of malformations in newborn and infant rats are not only permanent effects but are also highly correlated with serious reproductive malformations as adults. In summary, TB is a potent environmental androgen both in vitro and in vivo and, in contrast to other reports, can induce developmental abnormalities in the fetus.

Administration, Oral↗

Effects of castration on androstenedione, testosterone and dihydrotestosterone plasma levels in adult male rats.

In the present study we investigated the effects of castration on androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) plasma levels in adult male rats 5 and 47 days after castration. In another group of 60-day-old castrated rats, the three steroids have been evaluated during testosterone propionate administration. Our data show that 5 days after orchiectomy all three steroids were significantly decreased (p less than 0.001) with respect to control values. 47 days after orchiectomy, T and DHT were also significantly decreased with respect to the control group. In both groups of orchiectomized rats the A/T ratio increased significantly with respect to controls. On the contrary, the T/DHT ratio sharply decreased. This suggests that DHT, in orchiectomized rats, could derive from precursors other than T. A negative correlation between A and the T/DHT ratio was observed 47 days after castration in adult animals and emphasized upon testosterone propionate administration. In the latter group, T was significantly lower while A is significantly augmented with respect to control values. Finally, the above-mentioned negative correlation indicates a possible prevalent role of A in contributing to the circulating levels of DHT in adult orchiectomized rats.

Androstenedione↗

Influence of anabolic agents on protein synthesis and degradation in muscle cells grown in culture.

Muscle cell culture (L6) studies were conducted to determine whether anabolic agents have a direct effect on the muscle cell. The effects of zeranol, testosterone propionate, estradiol benzoate, progesterone, dexamethasone and anabolic agent-dexamethasone combinations on protein synthesis and degradation were measured. Myoblast and myotube cultures were pretreated with 1 microM compounds for 12, 24 and 48 h before a 6-h synthesis or degradation measuring period. Protein synthesis was determined as cpm of [3H] leucine incorporated per mg cell protein. Protein degradation was measured by a pulse-chase procedure using [3H] leucine and expressed as the percentage labeled protein degraded in 6 h. Progesterone slightly increased (P less than .05) protein synthesis in myoblast cultures. Testosterone propionate had no effect on synthesis. Protein synthesis was decreased by estradiol benzoate (P less than .01) in myotube cultures. Protein degradation was not altered appreciably by anabolic agents. Protein synthesis was initially inhibited in myotubes (P less than .05) by dexamethasone, but increased (P less than .01) in myoblasts and myotubes in the extended incubation time. Dexamethasone also consistently increased protein degradation, but this required several hours to be expressed. Anabolic agents did not interfere with dexamethasone-induced increases in protein synthesis and degradation. The magnitude of response and sensitivity were similar for both the myoblast and the more fully differentiated myotube for all compounds tested. These results indicate that anabolic agents at the 1 microM level do not have a direct anabolic effect on muscle or alter glucocorticoid-induced catabolic response in muscle.

Anabolic Agents↗

Effects of castration and androgens upon prostatic proteoglycans in rats.

In studies performed on male Wistar rats, castration induced atrophy of the prostate with a marked increase in the uronic acid content. The administration of testosterone propionate to castrated rats produced opposite effects. Fractionation of the glycosaminoglycans on cellulose microcolumns showed that the changes in uronic acid content in the dorsolateral lobes were due to variations in hyaluronic acid, chondroitin-4-sulfate, and dermatan sulfate, but in the ventral lobes, there were changes in all the chromatographic fractions. There were also changes in the physical properties of proteoglycans. In the ventral lobes, castration induced a wider distribution of molecular weight, increased density, and predominance of lateral chains of greater size. In the dorsolateral lobes, there was a decrease in molecular weight and density of proteoglycans and in the length of lateral chains. Opposite results were obtained when testosterone propionate was given to castrated rats. It is postulated that the effects of androgens upon prostatic growth would depend on an interrelationship between epithelium and stroma mediated by the proteoglycans.

Animals↗