Effect of testosterone and season on proenkephalin messenger RNA expression in the preoptic area of the hypothalamus in the ram.
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Enkephalin appears to exert an inhibitory action on LH secretion, but whether testosterone regulates enkephalin gene expression is unknown. This study tested the hypothesis that testosterone and/or season modulate preproenkephalin mRNA expression in specific areas of the hypothalamus. Romney Marsh rams were castrated (wethers) either during the breeding season or nonbreeding season and received intramuscular injections of either oil or testosterone propionate (five/group). Blood samples were taken for the assay of plasma LH and testosterone. Preproenkephalin mRNA expression was quantified in hypothalamic sections by in situ hybridization. Mean plasma LH concentrations were reduced and the interpulse interval for LH pulses was greater in testosterone propionate-treated wethers compared with oil-treated wethers, with no change in LH pulse amplitude. Testosterone propionate treatment reduced proenkephalin expression in the diagonal band of Broca, the caudal preoptic area, and the bed nucleus of the stria terminalis. Seasonal differences in proenkephalin expression were observed in the bed nucleus of the stria terminalis, lateral septum, periventricular nucleus, and paraventricular nucleus. No differences were observed between treatments in seven other regions examined. We conclude that testosterone and season regulate proenkephalin mRNA levels in the preoptic area/hypothalamus in the ram in a region-specific manner. (+info)
Expression and regulation of lipocalin-type prostaglandin d synthase in rat testis and epididymis.
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Lipocalin-type prostaglandin D synthase (L-PGDS), a bifunctional protein, is expressed in the male reproductive organs of many species. However, the expression and regulation of L-PGDS in rat are still uncertain. The present study investigated the regionalization and regulation of L-PGDS expression in rat testis and epididymis by in situ hybridization and immunohistochemistry under the conditions of sexual maturation, castration, and ethylene dimethane sulfonate (EDS) treatments. In sexually mature rats, L-PGDS mRNA was weakly expressed only in the testicular peritubular cells, whereas L-PGDS immunostaining was highly detected in the Leydig cells by Day 70 postpartum. During sexual maturation, L-PGDS mRNA expression was highly detected in the caput, corpus, and cauda of the epididymis 70 days after birth. Compared with normal L-PGDS expression in adult epididymis, both L-PGDS mRNA expression and protein immunostaining were significantly reduced in the caput, corpus, and cauda epididymis after castration. Testosterone propionate treatment induced a significant increase of L-PGDS expression in the epididymis of castrated rats. Compared with adult rat epididymis, L-PGDS mRNA and protein expression was down-regulated after EDS treatment. Testosterone propionate treatment could induce an increase of L-PGDS mRNA and protein expression in the epididymis of EDS-treated rats. In conclusion, both castration and EDS treatments caused a significant decrease of L-PGDS expression in the epididymis, whereas testosterone propionate treatment could induce an increase of L-PGDS expression in the epididymis of both castrated and EDS-treated rats, indicating that L-PGDS expression in the rat epididymis can be up-regulated by testosterone. (+info)
Equol is a novel anti-androgen that inhibits prostate growth and hormone feedback.
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Equol (7-hydroxy-3[4'hydroxyphenyl]-chroman) is the major metabolite of the phytoestrogen daidzein, one of the main isoflavones found abundantly in soybeans and soy foods. Equol may be an important biologically active molecule based on recent studies demonstrating that equol can modulate reproductive function. In this study, we examined the effects of equol on prostate growth and LH secretion and determined some of the mechanisms by which it might act. Administration of equol to intact male rats for 4-7 days reduced ventral prostate and epididymal weight and increased circulating LH levels. Using binding assays, we determined that equol specifically binds 5alpha-dihydrotestosterone (DHT), but not testosterone, dehydroepiandrosterone, or estrogen with high affinity. Equol does not bind the prostatic androgen receptor, and has a modest affinity for recombinant estrogen receptor (ER) beta, and no affinity for ERalpha. In castrated male rats treated with DHT, concomitant treatment with equol blocked DHT's trophic effects on the ventral prostate gland growth and inhibitory feedback effects on plasma LH levels without changes in circulating DHT. Therefore, equol can bind circulating DHT and sequester it from the androgen receptor, thus altering growth and physiological hormone responses that are regulated by androgens. These data suggest a novel model to explain equol's biological properties. The significance of equol's ability to specifically bind and sequester DHT from the androgen receptor have important ramifications in health and disease and may indicate a broad and important usage for equol in the treatment of androgen-mediated pathologies. (+info)
Androgens increase spine synapse density in the CA1 hippocampal subfield of ovariectomized female rats.
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The effects of androgen on the density of spine synapses on pyramidal neurons in the CA1 area of the hippocampus were studied in ovariectomized (OVX) adult female rats. Treatment of OVX rats with testosterone propionate (TP; 500 microg/d, s.c., 2 d) significantly increased spine synapse density (from 0.661 +/- 0.016 spine synapse/microm3 in OVX rats to 1.081 +/- 0.018 spine synapse/microm3 after TP treatment). A smaller, but still statistically significant, increase in synapse density (0.955 +/- 0.029 spine synapse/microm3) was observed in OVX animals after treatment with the nonaromatizable androgen dihydrotestosterone (DHT; 500 microg/d, s.c., 2 d). Administration of 1 mg of letrozole, a powerful nonsteroidal aromatase inhibitor, 1 hr before the steroid injections almost completely blocked the synaptic response to testosterone, resulting in a mean synapse density (0.723 +/- 0.003 spine synapse/microm3) only slightly higher than in OVX control rats. By contrast, the response to DHT was unaffected by letrozole pretreatment. These data suggest that androgen secretion during the female reproductive cycle may contribute to cyclical changes in hippocampal synaptic density. They also indicate that androgen treatment may be as effective as estrogen replacement in reversing the decline in hippocampal CA1 spine synapses that follows loss of ovarian function. Induction of hippocampal synapse formation by androgen is not mediated entirely via intracerebral estrogen biosynthesis, however, because aromatase-independent mechanisms also significantly affect CA1 spine synapse density. (+info)
Interactive effects of vinclozolin and testosterone propionate on pregnancy and sexual differentiation of the male and female SD rat.
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In mammals, androgens are essential in directing mammalian sexual differentiation of the male phenotype. Administration of testosterone during this period alters female development in a male-like direction, whereas exposure to an androgen receptor antagonist like vinclozolin (V) demasculinizes and feminizes the male offspring. In the current study, we administered V (gavage at 200 mg/kg/day) and/or testosterone propionate (TP, sc, at 1 mg/rat/day), alone and in combination to Sprague-Dawley (SD) rats on days 14 through 19 of pregnancy, to determine if V would antagonize the effects of TP in the female and, conversely, if TP would antagonize the effects of V in the male offspring. These doses of TP and V were selected because they significantly alter sexual differentiation in the majority of female and male rat offspring, respectively, without producing severe toxicity in the dam or offspring. The study design is a 2 x 2 factorial (7 dams per group) including vehicle control, V, TP, and V + TP groups. As expected, individually, both V and TP reduced maternal weight gain and the V + TP group was affected in a cumulative fashion. Litter size on postnatal day (PND) 2 was reduced only by V + TP, whereas pup body weight was reduced in all three treated groups, the effect of V + TP again being cumulative. In female offspring, TP-induced alterations (i.e., increased anogenital distance [AGD] and fewer nipples, vaginal agenesis, hydrometrocolpos, induced prostate and bulbourethral glands, and levator ani muscle tissues) were all reversed by coadministration of V. In male offspring, V-induced alterations were only modestly antagonized by TP. At the dosage levels used herein, V + TP-treated male offspring had less well-developed nipples as infants and adults and a lower incidence of ectopic testis than did the V group. However, V-induced changes in reproductive organ weights, AGD, atrophic testes, vaginal pouch, and agenesis of the sex accessory tissues were not antagonized by concurrent TP treatment in male offspring. We observed that the combination of V and TP, two chemicals with opposing endocrine action, antagonized one another during sexual differentiation, especially in the female offspring and induced cumulative effects on maternal and neonatal toxicity. We suspect that antagonism of V by TP would be enhanced in the male if lower dose levels of V were used, but then the antagonism of TP by V in the female would likely be attenuated. (+info)
Enhanced rat Hershberger assay appears reliable for detection of not only (anti-)androgenic chemicals but also thyroid hormone modulators.
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Development of an internationally recognized standard for the Hershberger assay as a screening tool to detect potential (anti-)androgenic chemicals is in progress. In the present preliminary study, we evaluated the reliability of the enhanced Hershberger assay to detect thyroid hormone modulating activity, while concentrating attention on possible confounding influence on evaluation of (anti-)androgenic activity. Castrated or testosterone propionate (TP; 0.2 or 0.25 mg/kg/day)-injected castrated male Crj:CD(SD) IGS rats (seven weeks of age) were dosed for 10 days by oral gavage with vehicle (corn oil) or the following chemicals: propylthiouracil (PTU; 2.5 mg/kg/day), a potent inhibitor of thyroid hormone synthesis, phenobarbital (PB; 125 mg/kg/day) and 2,2-bis(4-chlorophenyl)-1,1-dichloroethylene (p,p'-DDE; 100 mg/kg/day), two hepatic enzyme inducers that enhance the clearance of thyroid hormones. PTU markedly increased thyroid weights, and decreased serum T3 and T4, and increased serum TSH, also causing marked microscopic alteration of the thyroid gland. In comparison, PB and p,p'-DDE only significantly affect serum T4 and revealed some histopathological findings. The alterations appeared to be more robust in the presence of TP. Furthermore, data for p,p'-DDE demonstrated its anti-androgenic effects, whereas PTU and PB had little or no effects on the weights of androgen-related accessory glands/tissues: the ventral prostate, dorso-lateral prostate, seminal vesicles with coagulating glands, glans penis, Cowper's glands, and levator ani plus bulbocavernosus (LABC) muscles. Weight of the LABC muscles was decreased by PB treatment in TP-treated castrated rats. These findings in the present study suggests that the enhanced Hershberger assay, with evaluation of thyroid histopathology and weights, and hormone levels, appears to be reliable for screening for not only (anti-)androgenic chemicals but also thyroid hormone modulators. In order to evaluate whether the sensitivity and specificity of such a thyroid assay is great enough for routine screening purposes, future experiments including dose-response studies using lower dose levels have to be performed. (+info)
Effect of baicalein on experimental prostatic hyperplasia in rats and mice.
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We determined the effect of baicalein on prostatic hyperplasia in experimental animal models. Prostatic hyperplasia was induced by testosterone propionate in mice and castrated rats and by transplantation of homologous strain fetal mice urogenital sinus in mice. With the histopathological examination, the efficacy of baicalein on prostate hyperplasia in experimental animals was evaluated by the activity of serum acid phosphatase (ACP) and the following norm of the prostate gland: the volume, wet weight, wet weight index, dry weight index, DNA contents and prostatic epithelial height and cavity diameter. Results showed that baicalein at doses of 260 and 130 mg/kg administrated intragastrically (i.g.) significantly inhibited prostatic hyperplasia in castrated rats induced by testosterone propionate compared with the negative control group (p<0.01). Baicalein at doses of 520 and 260 mg/kg (i.g.) also significantly inhibited prostatic hyperplasia in mice induced by transplantation of homologous strain fetal mouse urogenital sinus and by testosterone propionate (p<0.01). These results suggested that baicalein has an inhibitory effect on prostatic hyperplasia in experimental animals. (+info)
Expression of hypothalamic arginine vasotocin gene in response to water deprivation and sex steroid administration in female Japanese quail.
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Arginine vasotocin (AVT) is a neurohypophyseal hormone involved in reproductive function and control of osmoregulation in birds. In view of the dual function of AVT, the present experiment was designed to observe the effect of water deprivation (WD) and sex steroid [estradiol benzoate (EB) and testosterone propionate (TP)] treatment independently, as well as simultaneously, on the profile/activity of the hypothalamic AVT system. WD resulted in a significant increase in plasma osmolality, sodium ion concentration and AVT concentration, but administration of sex steroids had no significant influence on these parameters. By contrast, the amount of hypothalamic AVT transcript (northern analysis) and the size of immunoreactive vasotocin (ir-AVT) neurons and hybridization signals (in the form of silver grains), representing AVT mRNA in corresponding neurons of paraventricular nuclei (PVN), increased significantly in all the treated groups compared with controls. Our findings indicate that although sex steroid administration has no effect on plasma osmolality and AVT concentration, unlike water deprivation, it may stimulate the profile/activity of AVT neurons of PVN, supporting the possibility of sex steroid receptors on these neurons. It is concluded that in quail, osmotic stress not only upregulates the expression of the AVT gene in existing neurons but also recruits many more neurons to increase the rate of AVT synthesis and secretion, while sex steroids appear to have a stimulatory effect only on the existing number of neurons and only at the level of transcription/translation and hence may influence/modulate hypothalamic AVT gene expression in response to osmotic stress. This study also suggests an interrelationship between reproduction and AVT system/function in birds. (+info)