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Decreased fructose concentrations in coagulating glands of prepuberal rats treated with testosterone and LH.

Doses of testosterone propionate from 2.5 to 320 microgram and doses of LH from 2 to 360 microgram given over 1--3 days generally decreased fructose/body weight ratios in the coagulating glands of late prepuberal rats. The ratios of testes, seminal vesicles, coagulating glands and ventral prostates to body weight were increased after different treatment regimes with testosterone propionate. These changes in the variables measured could be detected by computer analysis in spite of the rapid growth rates of organs of rats of this age. LH increased the weights of only the seminal vesicles and coagulating glands, and then, only at the highest doses given.

Animals↗

The response of the sebaceous glands of female rats ovariectomized at birth to testosterone.

Newborn Sprague-Dawley rats were ovariectomized within 24 h of birth and control animals were sham-operated. Immediately, one-half of the rats in each group received a single injection of 500 micrograms testosterone propionate. The other half acted as a vehicle control. Normal male and female rats were also included for comparison. The secretion rate of sebum was measured at the age of 80 days from the amount of skin-surface lipids that could be extracted with acetone and which had been produced during 2 days. Male rats secreted more sebum than female rats. In female rats, irrespective the presence or absence of ovaries, when treated with a single injection of testosterone propionate at birth, although secreted significantly more sebum than vehicle control groups, the increase was still far below the level normally found in the male. On the other hand, implantation of testosterone pellet at the age of 4 weeks in neonatally ovariectomized-androgenized female rats greatly increased sebum secretion to an extent far exceeding that of the normal male rats. It is concluded that testosterone can directly increase sebum secretion in the female rats irrespective the presence or absence of ovaries when given at birth and reinforcement at about puberty produces a full effect of secretion.

Animals↗

Control of uterine estrogen receptor levels by progesterone.

The mechanism by which progesterone antagonizes estrogenic stimulation of uterine growth was examined in the immature rat. Rats received daily injections of 2.5 mug estradiol (E) for 2 days and on day 3 either 2.5 mug E or 2.5 mug E plus 2.5 mg of progesterone (P). The quantity of nuclear and cytoplasmic estrogen receptor was determined by [3H]estradiol exchange at various intervals after injection of E or E + P. In both groups, nuclear receptor estrogen complex (RnE) increased dramtically one hour after injection and showed a gradual decline from 4 to 24 h after injection. The quantity of cytoplasmic receptor, Rc, decreased to low levels by one hour and began a gradual increase from 4 to 8 h in both groups. However, between 8 and 24 h after injection, the level of Rc continued to increase in the E treatment group (2.39 +/- 0.21 pmol/uterus at 24 h) but remained at the 8 h level in the E + P group (1.09 +/- 0.04 pmol/uterus at 24 h). This observation suggests that two seperate processes are involved in the replenishment of Rc and that progesterone inhibits the second phase of replenishment. The binding affinity and specificity of Rc for estrogens following E + P pretreatment were identical to those of the E pretreatment group. Therefore, P does not alter the binding properties but rather the intrauterine level of Rc. Treatment with E on day 4, when Rc levels differ between E and E + P groups, stimulated uterine weight and protein content on day 5 in the E pretreatment group. However, minimal stimulation was observed in the E + P pretreatment group. The quantity of RnE and the time of nuclear retention of RnE following E injection on day 4 was greater in the E group than in the E + P group. The effect of progesterone on Rc replenishment was dose-dependent (range, 0.1-2.5 mg; 1/2 maximal, 0.5 mg). Injection of testosterone propionate (1.0 mg), a weak estrogen antagonist, with E on day 3 resulted in slightly reduced levels of Rc on day 4. This reduction also correlated with a reduced sensitivity to treatment with E on day 4. These data, together with previous studies from our laboratory, suggest that progesterone and other estrogen antagonists such as nafoxidine and testosterone propionate inhibit estrogen action by interfering with the replenishment of Rc, thereby reducing the number of receptor estrogen complexes that are translocated and retained by uterine nuclei.

Animals↗

The topical administration of steroids in the treatment of typical vulvar dystrophies.

Sixty-eight patients with histologically diagnosed typical vulvar dystrophies were treated with local administration of steroids. Twenty-three patients with hyperplastic dystrophies received topical fluorinated corticosteroids twice a day for 4 weeks and once a day for another 2 weeks. Thirty-five patients with lichen sclerosus were given local 2% testosterone propionate in vaseline twice a day for 8 weeks, once a day for another 8 weeks and then 3 times a week for another 8 weeks. Ten patients with mixed dystrophy first received topical fluorinated corticosteroids twice a day for 4 weeks and once a day for another 2 weeks, and then local 2% testosterone propionate in vaseline twice a day for 4 weeks and once a day for another 4 weeks. A relief of symptomatology and a regression of gross appearance were obtained in 82.6% and 69.6% of patients respectively with hyperplastic dystrophy, in 82.9% and 65.7% of those with lichen sclerosus and in 80% and 40% of those with mixed dystrophy. A recurrence of symptomatology often occurred at various times after the end of therapy.

Administration, Topical↗

The hormone-sensitive early postnatal periods for sexual differentiation of feminine behavior and luteinizing hormone secretion in male and female rats.

The purpose of this study was to determine the duration of the hormone-sensitive postnatal period during which a single injection of testosterone propionate (TP) influences feminine behavior and luteinizing hormone (LH) secretion in male and female rats. Male pups were castrated on the day of birth (day 1) between 6 and 12 h postpartum. On postnatal day 3, 4, 5, 6, 7, 8, or 9 female pups and castrated males (fales) were injected subcutaneously with testosterone propionate (TP-500 micrograms). The females were laparotomized at 60 days of age, and ovarian tissue was removed for histological analysis. Female behavior was evaluated at 100 days of age. At 150 days of age, the ability of steroids to facilitate LH secretion was determined. Tests for lordosis indicated a diminished lordotic quotient (LQ) with both females and fales treated with TP on postnatal day 3, 4, 5, 6, or 7. On day 8 or 9, however, the lordotic response was at control levels. Females in all TP treated groups had significantly reduced number of corpora lutea. Females and fales treated with TP on postnatal day 3, 4, 5, 6, 7, 8, or 9 failed to exhibit an LH surge as adults. The results indicate that the neural control of feminine behavior (LQ) is hormone-sensitive to a single injection of TP up through the 7th day of postnatal life, whereas the neural substrate regulating LH secretion was sensitive in the present study at least up through day 9 in both fales and females.

Animals↗

[Interaction of androgen-receptor complexes in rat liver cytosol with cellular nuclei and DNA].

A study was made of the ability of androgen-receptor complexes (ARC) of male rat liver cytosol to interact with hepatic cell nuclei and DNA in a model free-cell system and after administration of androgens to animals. In a free-cell system androgen receptors (AR) within a partially purified cytosol preparation were capable of binding strongly with hepatic cell nuclei and DNA of cellulose-conjugated cow spleen. The administration of testosterone propionate for 3 days resulted in the redistribution of liver AR between cytoplasm and nuclei during testing 1 h after the last injection. The observed regularities were unrelated to changes in AR content caused by the regulatory effect of administered androgen. Similar changes in AR content in the studied subcellular fractions were revealed 1 h after single administration of R1881 but not testosterone propionate. The revealed regularities were indicative of a possibility of AR involvement in androgenic action on the liver at the nuclear level.

Androgens↗

Sexual differentiation of aromatase activity in the rat brain: effects of perinatal steroid exposure.

Androgens regulate aromatase activity in the medial preoptic area and other components of the brain circuit that mediates male sexual behavior. The levels of aromatase activity within these brain regions are greater in males than in females. As the activation of copulation requires aromatization of testosterone to estradiol, this quantitative enzymatic difference between sexes could contribute to the greater behavioral response displayed by males. The present study was designed to test the hypothesis that gender differences in brain aromatase activity of adult rats are dependent on the sexual differentiation of the brain that occurs during perinatal exposure to gonadal hormones. Aromatase activity was measured in vitro in microdissected brain samples using a sensitive radiometric assay. We examined the effect of pre- and postnatal treatment with testosterone propionate or diethylstilbestrol on basal levels and androgen responsiveness of aromatase in adults. In addition, we examined what effect prepubertal gonadectomy exerts on enzyme regulation. Our results demonstrate that perinatal treatments with gonadal hormones that are known to differentiate sexual behavior can completely masculinize the capacity for aromatization in the adult female. The process that differentiates aromatase expression appears to depend on androgen exposure and, in part, local estrogen synthesis, as diethylstilbestrol was able to substitute for testosterone propionate. We also observed that prepubertal gonadectomy reduced the levels of aromatase activity measured in adult brain, suggesting that gonadal hormones that are secreted during puberty may enhance the expression of aromatase activity in adulthood. From this study, we conclude that testosterone and/or its estrogenic metabolites act on the developing brain to determine the gender-specific capacity for aromatization and to regulate androgen responsiveness within components of the neural circuitry that mediates male sexual behavior.

Animals↗

Control of glycolytic enzymes by androgens in the rat epididymis.

The influcnce of steroids on the specific activities of glycolytic enzymes was studied in the caput and cauda epididymidis of the rat. In castrated animals, increases in enzyme activities were induced by the administration of androgenic steroids whilst oestradiol and progesterone were without effect. On the other hand, the "antiandrogenic" steroid, cyproterone acetate (16 mg/kg per day for 2 weeks) did not cause a decrease in enzyme activities when administered to animals with ligated efferent ducts. Not all glycolytic enzymes responded to androgens, but more enzymes responded in the caput than in the cauda epididymidis. Administration of testosterone propionate to castrated animals demonstrated that maximum enzyme activity was produced at a dose of 0-1 mg/kg per day whilst higher doses were required to achieve maximum weight of the epididymis, seminal vesicles and prostate. Following castration of animals with ligated efferent ducts, no changes in enzyme activities were observed for approximately 2 days, but then activities declined over the next 2 weeks. When testosterone propionate was administered to castrated animals, a similar lag of approximately 2 days occurred before enzyme activities began to increase.

Androgens↗

Testosterone is more effective than dihydrotestosterone plus estradiol in activating sexual behavior in old male rats.

Sexual behavior declines in old male rats, and testosterone therapy does not restore the behavior to levels found in young males. If as a result of aging, old males have less capacity to aromatize or reduce testosterone, dihydrotestosterone plus estradiol treatment should be more effective than testosterone treatment in restoring sexual behavior in old castrated males. In a test of this hypothesis, the sexual behavior of old (24 months) castrated Fischer 344 males given injections of testosterone propionate (TP) or dihydrotestosterone propionate (DHTP) plus estradiol benzoate (EB) and that of old sham-operated males given injections of vehicle were observed. The DHTP/EB proved to be less effective overall than the TP in increasing sexual behavior in old castrated males. In a second experiment, young (3 months) and old (30 months) males were tested to verify that the reduced effectiveness of DHTP/EB treatment was age-related. Testosterone propionate and DHTP/EB were equally effective in restoring most measures of sexual behavior in young castrated males. In old castrated males, DHTP/EB treatment was no more or less effective than TP treatment in increasing these same measures. Neither hormone increased the behavior of old males to the level found in young males. Since DHTP/EB treatment is less effective than TP treatment in stimulating sexual behavior in old males, a reduced capacity to aromatize or reduce testosterone is not a likely explanation for decreased responsiveness to testosterone in old male rats.

Aging↗

Effects of Danazol on the epididymal function in male langurs (Presbytis entellus entellus Dufresne).

Danazol (28 mg/kg body weight) was administered intramuscularly (i.m.) to intact langurs for a period of 48 days. Epididymides weight showed no significant change but tubular lumina were devoid of spermatozoa. These effects were reversible after 180 days of recovery period. Possible antiandrogenic action of the drug was evaluated by administering Danazol in conjunction with testosterone propionate (TP) (0.7 mg/kg body weight) to castrated langurs. Biochemical estimations for total protein and sialic acid contents showed a significant fall in all the treated groups. Whereas, alkaline phosphatase activity was increased in Danazol treated langurs and a decrease was noticed in castrates, which returned to near normal level after recovery period in intact and TP treatment in castrates. In conclusion, the present findings demonstrate that Danazol effectively suppressed the action of testosterone propionate in castrates. The inhibitory effects of Danazol on steroidogenesis in intact langurs might be due to biochemical interaction at subcellular system.

Alkaline Phosphatase↗

The impact of prenatal androgens on vaginal and urogenital sinus development in the female mouse.

PURPOSE: In females abnormal urogenital virilization can occur secondary to prenatal exposure to exogenous or endogenous androgens. We studied the effects of different doses of prenatal androgens on urogenital sinus development and the location of the vaginal confluence in a mouse model. MATERIALS AND METHODS: Timed pregnant C57/6 mice were exposed to 2, 5 and 10 mg testosterone propionate on gestational days 14 through 18. On gestational day 19 the genital tubercles and internal genitalia were examined grossly and histologically for the presence of virilization. Three-dimensional computer reconstruction was done and plastic cast injection molds of the urogenital sinus were made in select specimens. RESULTS: Microscopic analysis confirmed the spectrum of virilization, which occurred in 98% of testosterone propionate treated female fetuses. Plastic cast injection showed that affected females had a longer urogenital sinus, more proximal confluence and shorter vagina in a dose dependent manner. Histological sections and 3-dimensional reconstruction revealed that the bladder neck moved proximal under the pubic bone, also in a dose dependent manner. CONCLUSIONS: Prenatal exposure to increasing levels of androgen causes urogenital sinus elongation in a female mouse fetus. In the mouse model the confluence area moves proximally together with the bladder neck in a dose dependent manner.

Animals↗

Crowding or ACTH treatment of pregnant mice affects adult copulatory behavior of male offspring.

Sexual behavior of male offspring from female mice chronically crowded during Days 12-17 of pregnancy was investigated. In an 80-min test pairing with a sexually experienced female primed with estradiol and progesterone injections, males from crowded mothers displayed poorer copulation than controls: mount and intromission latencies were longer, number of mounts and intromissions lower, and ejaculations within the test period were abolished. Daily injections of 500 micrograms testosterone propionate improved copulatory vigor in offspring from crowded mothers. A second series of experiments investigated the effects of ACTH treatment of females during the same period of pregnancy. A low dose rate (1 IU injected daily) had little effect but male offspring from females injected daily with 8 IU displayed longer intromission latency and fewer mounts and intromissions than controls. Daily injections of 500 micrograms testosterone propionate improved copulatory vigor, although mount frequency remained depressed. The similarity of the effects on male offspring copulation of crowding their mothers during pregnancy or ACTH treatment during pregnancy suggest mediation by similar mechanisms, implicating involvement of maternal pituitary-adrenocortical secretions during pregnancy in the production of these behavioral deficits. Postnatal influences were minimized by fostering all litters at birth to untreated dams.

Adrenocorticotropic Hormone↗

Induction of nest-material collecting in male Barbary doves by intracerebral androgen.

The behaviour of the male Barbary dove (Streptopelia risoria) in selecting nesting material and transporting it to the nest site is reduced after castration and is restored by treatment with testosterone propionate when castrated males received unilateral intracerebral implants of this androgen. Implants in the anterior hypothalamus, preopitc region, and the area of the ventral neostriatum intermediale were effective in reinstating the collection of nesting material, and in many instances restoration of the behaviour was to levels at or above those observed before castration. Implants in other areas, and implants without hormone, were generally without effect. Although the brain areas from which the gathering of nesting material can be elicited are comparable to those from which courtship displays have been induced in previous studies, it appears that testosterone propionate implants stimulate nesting activities more effectively and more persistently than courtship.

Animals↗

Effect of castration and steroid replacement on immunoreactive luteinizing hormone cells in the pars tuberalis of the rat.

The response of LH cells in the pars tuberalis of the rat hypophysis to castration alone or castration and subsequent administration of testosterone propionate or estradiol benzoate was studied. To accomplish this, LH cells were labeled by the peroxidase-antiperoxidase immunocytochemical method, with use of an antiserum generated against hCG. LH cells were detected in the caudal region of the pars tuberalis of all intact control animals studied. After castration, LH cells in both the pars distalis and pars tuberalis showed similar degrees of hypertrophy and hyperplasia. This response was inhibited by either testosterone propionate or estradiol benzoate in the pars distalis as well as in the pars tuberalis. These results indicate that LH cells in the pars tuberalis, in addition to those in the pars distalis, are responsive to fluctuations in circulating steroid hormone levels and that the pars tuberalis may contribute to the overall secretion of gonadotropin by the adenohypophysis.

Animals↗

Differential expression of the tetracycline-controlled transactivator-driven human CYP1B1 gene in double-transgenic mice is due to androgens: application for detecting androgens and antiandrogens.

Differential expression of the tetracycline-controlled transactivator (tTA)-driven human cytochrome p450 (CYP) 1B1 gene was found in the livers of male mice, at high levels in neonates, but at low levels in adults. The goals of this study were to determine whether the differential expression of the tTA-driven human CYP1B1 (hCYP1B1) gene in neonates and adults was testosterone dependent and whether flutamide, a representative potent antiandrogen, led to the induction of hCYP1B1. This was tested by treating castrated transgenic mice with testosterone propionate and musk extracts. It was concluded that: (i). the levels of expression of both tTA and hCYP1B1 gradually declined, with clear changes being apparent between 2 and 4 weeks of age, (ii). castration of adult males resulted in the increased expressions of both tTA and hCYP1B1 to levels similar to those found in adult females, (iii). treatment of castrated male and adult female mice with testosterone propionate and musk extracts led to the restoration of the levels of expression of hCYP1B1 in the adult males, and (iv). treatment of adult males with flutamide caused an increase in the levels of expression of hCYP1B1 in the adult females, as indicated by the antiandrogenic activity. Thus, the differential expression of the tTA-driven hCYP1B1 gene in the transgenic mice was caused by androgen, and it is possible that castrated male and adult female mice expressing the tTA-controlled hCYP1B1 could be used as the basis for a strategy for the detection of androgens and antiandrogens.

Aging↗

Effect of neonatal testosterone and oestradiol treatment on the development of the hypothalamo-hypophysial axis in the female rat.

The hypothalamic LH-RH content and the concentrations of pituitary and plasma LH were measured at various ages in female rats treated daily with 10 micrograms testosterone propionate or 10 micrograms oestradiol-17beta from birth to Day 15. Persistent vaginal oestrus was induced in all the treated rats. Both hormones significantly reduced the hypothalamic LH-RH content and pituitary and plasma LH concentrations. Hypothalamic LH-RH increased after cessation of treatment but pituitary LH did not return to normal levels. Plasma LH levels were significantly lower than those in control rats. It is concluded that testosterone propionate and oestradiol-17beta (1) have a direct negative feed-back influence on the hypothalamus in the neonatal female rat; (2) alter the normal pattern of plasma and pituitary LH in developing female rats; (3) prevent the cyclic secretion of plasma LH after maturity; and (4) probably cause a chronic impairment in the release of LH-RH.

Animals↗

[An experimental study(I) on the inhibition of prostatic hyperplasia with extract of seeds of Brassica alba].

OBJECTIVE: To study the effective fraction of the extract of seeds of Brassica alba, which inhibits experimental mice prostatic hyperplasia. METHOD: An experimental model of prostatic hyperplasia of castrated male mice induced by testosterone propionate was made. Fractions I, II and III were prepared by extracting the seeds of Brassica alba successively with ether, ethanol and water under reflux. Total extract was prepared by extracting the seeds of Brassica alba with 60% ethanol under reflux. The total extract and the three fractions were used to test the activities. RESULT: Total extract, fractions I and II could not only significantly inhibit mice prostatic hyperplasia induced by testosterone propionate and activity of serum acid phosphatase, but also decrease wet weight of preputial glands, while fraction III is inactive. CONCLUSION: Extract from seeds of Brassica alba can significantly inhibit mice prostatic hyperplasia induced by exterior hormone, possessing an activity of anti-androgen. Fractions I and II show an equivalent activity of total extract, which indicate that these fractions contain active components of seeds of Brassica alba which can inhibit prostatic hyperplasia.

Acid Phosphatase↗

Postnatal development, sex-related difference and hormonal regulation of acetohexamide reductase activities in rat liver and kidney.

A variety of patterns of postnatal development were observed for acetohexamide reductase activities in microsomes and cytosols from the liver and kidney of male and female rats. Furthermore, there were pronounced sex-related differences in the activities of liver and kidney microsomes. Prepubertal and neonatal testectomies decreased markedly the activities in liver and kidney microsomes of adult male rats to the female levels. The activities in liver and kidney microsomes decreased by prepubertal testectomy and the activity in kidney microsomes decreased by neonatal testectomy were restored to control levels by testosterone propionate treatment, whereas the activity in liver microsomes decreased by neonatal testectomy was unaffected by the same treatment. Prepubertal or neonatal testectomy had no effect on the activity in liver or kidney cytosol of adult male rats. Prepubertal ovariectomy decreased the activities in liver and kidney cytosols of adult female rats and the decreased activities were restored to control levels by estradiol benzoate treatment. Based on these results, we propose that the postnatal development and sex-related difference of acetohexamide reductase activities in rat liver and kidney can be regulated by sex hormones such as testosterone propionate and estradiol benzoate.

Alcohol Oxidoreductases↗