RESUMEN
Puberty is a transitional period from juvenile stage to adulthood, followed by the functional maturation of gonads and reproductive organs. This period is sensitive to environmental pollutants like cadmium (Cd), a heavy metal that represents a serious health risk. Cd is an endocrine disruptor that interferes with reproduction by causing oxidative stress in the reproductive organs, affecting the sexual function and decreasing testosterone (T) levels. However, little research has been done on the effects of Cd on puberty markers and antioxidant systems. In this study, we evaluated the effects of Cd on puberty markers: preputial separation, testes descent and T levels, and the antioxidant activity (SOD, CAT, GSH/GSSG and TAC) in the seminal vesicles, testis and epididymis. Male Wistar pups were treated with 1â¯mg/kg Cd or saline solution by i.p. injection from day 1 to 35; the other treatment was administrated for 49 days. At the end of treatment, the animals were sacrificed, and the tissues of interest dissected, weighed and prepared for the respective assays. Cd treated rats from birth to puberty showed a delay onset in the puberty markers and a low weight in reproductive organs. Also, Cd induced differential effects on the redox system in reproductive organs and decreased T levels, these effects played a pivotal role in the delay of puberty markers onset (testes descent and preputial separation), affecting the development and sexual maturity of the male rats.
Asunto(s)
Cadmio/toxicidad , Contaminantes Ambientales/toxicidad , Epidídimo/efectos de los fármacos , Vesículas Seminales/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Cadmio/sangre , Catalasa/metabolismo , Epidídimo/crecimiento & desarrollo , Epidídimo/metabolismo , Glutatión/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Oxidación-Reducción , Ratas Wistar , Vesículas Seminales/crecimiento & desarrollo , Vesículas Seminales/metabolismo , Superóxido Dismutasa/metabolismo , Testículo/crecimiento & desarrollo , Testículo/metabolismo , Testosterona/sangreRESUMEN
Testis-specific serine kinases (TSSKs) are a family of serine/threonine kinases highly expressed in the testes that are responsible for regulating many spermatogenesis-related protein activities. Mutations in this family have a positive relationship with oligospermia and azoospermia in human and mouse. Here, five members of the TSSK family from a Banna mini-pig inbred line (BMI) were cloned, sequenced, and characterized. The full-length coding sequences of BMI TSSKs varied from 807 (TSSK3) to 1095 bp (TSSK1) and encoded 268 to 364 amino acids with molecular weights in the range 30.11 to 41.34 kDa. Following comparison with TSSK4 genes in other species, BMI TSSK4 was found to contain three alternatively spliced variants, inform1, inform 3, and inform 4. BMI TSSK1 and TSSK2 are co-localized on the Sus scrofa chromosome (SSC) 14, and consist of a single exon; TSSK3, TSSK4, and TSSK6 are on SSC6, SSC7, and SSC2, and consist of two, four, and one exon, respectively. Multiple protein sequence alignment and phylogenetic analysis showed that the regions spanning the S_TKc domains were more conserved between pig and other animals: with TSSK1 and TSSK2 and TSSK3 and TSSK6 displaying the greatest degree of homology across species, and the TSSK4 protein clearly distinct from other members. Multi-tissue RT-PCR showed BMI TSSK1, TSSK3, and TSSK4 were only expressed in the testes and seminal vesicle, TSSK2 was confined to testes only, while TSSK6 was expressed widely in adult tissues but was highest in the testes.
Asunto(s)
Familia de Multigenes/genética , Proteínas Serina-Treonina Quinasas/genética , Espermatogénesis/genética , Testículo/crecimiento & desarrollo , Adulto , Secuencia de Aminoácidos/genética , Animales , Clonación Molecular , Regulación del Desarrollo de la Expresión Génica , Humanos , Masculino , Ratones , Especificidad de Órganos/genética , Filogenia , Proteínas Serina-Treonina Quinasas/biosíntesis , Vesículas Seminales/crecimiento & desarrollo , Vesículas Seminales/metabolismo , Porcinos , Porcinos Enanos , Testículo/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Tropaeolum majus L. (Tropaeolaceae) is a medicinal herb popularly used in Brazil for treatment of inflammatory and cardiovascular diseases. Despite some published data on its efficacy, there are still few toxicological data describing the safety of this plant. The aim of this study was to evaluate the (anti)estrogenic and (anti)androgenic activity of the hydroethanolic extract obtained from Tropaeolum majus L. (HETM), as well as its possible effects on uterine contractility. MATERIALS AND METHODS: Three experimental protocols were performed, (a) uterotrophic assay, (b) Hershberger assay and (c) an ex vivo test to investigate the effects of maternal administration of HETM on uterine contractility at the end of pregnancy. In all protocols three doses of the HETM were administered to Wistar rats: 3, 30 and 300mg/kg. RESULTS: In vivo tests for detection of (anti)androgenic and (anti)estrogenic activities did not show any significant alterations. Similarly, no alterations were observed on uterine contractility induced by oxytocin and arachidonic acid. CONCLUSIONS: HETM was unable to produce (anti)estrogenic or (anti)androgenic activities in the short-term in vivo screening assays performed. In addition, there was no evidence that HETM can affect uterine contractility following gestational exposure of rats.
Asunto(s)
Antagonistas de Andrógenos/farmacología , Andrógenos/farmacología , Moduladores de los Receptores de Estrógeno/farmacología , Estrógenos/farmacología , Extractos Vegetales/farmacología , Tropaeolaceae , Contracción Uterina/efectos de los fármacos , Antagonistas de Andrógenos/administración & dosificación , Antagonistas de Andrógenos/aislamiento & purificación , Andrógenos/administración & dosificación , Andrógenos/aislamiento & purificación , Animales , Moduladores de los Receptores de Estrógeno/administración & dosificación , Moduladores de los Receptores de Estrógeno/aislamiento & purificación , Estrógenos/administración & dosificación , Estrógenos/aislamiento & purificación , Etanol/química , Femenino , Edad Gestacional , Masculino , Exposición Materna , Orquiectomía , Oxitócicos/farmacología , Pene/efectos de los fármacos , Pene/crecimiento & desarrollo , Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Embarazo , Próstata/efectos de los fármacos , Próstata/crecimiento & desarrollo , Ratas , Ratas Wistar , Vesículas Seminales/efectos de los fármacos , Vesículas Seminales/crecimiento & desarrollo , Solventes , Tropaeolaceae/química , Útero/efectos de los fármacos , Útero/crecimiento & desarrolloRESUMEN
The aim of this study was to ascertain the inhibitory effect of several progesterone derivatives for 5 alpha-reductase types 1 and 2 isozymes and to determine the binding to the androgen receptor. The 3,20-dioxopregna-4-ene-17 alpha-yl acetate 4 containing an acetoxy group in C-17 and steroid 17 alpha-hydroxypregn-4-ene-3,20-dione 5 having a hydroxyl group in the same position inhibited both isozymes. On the other hand, 17 alpha-hydroxy-4,5-epoxypregnan-3,20-dione 6 with an epoxy function at C-4, inhibited only the type 1 enzyme. Steroid 4-chloro-17 alpha-hydroxypregn-4-ene-3,20-dione 7a and 4-bromo-17 alpha-hydroxypregn-4-ene-3,20-dione 7b having the C-4 conjugated system and a chlorine or a bromine atom at C-4 respectively, inhibited both types of 5 alpha-reductase. These results indicate that an increase in the electronegativity of ring A produces a major inhibitory activity for 5 alpha-reductase type 1; however this increase was not observed for type 2 enzyme. When the free hydroxyl group of 7a or 7b was esterified, compounds 3,20-dioxo-4-chloropregn-4-ene-17 alpha yl-4-ethylbenzoate 8a and 3,20-dioxo-4-bromopregn-4-ene-17 alpha yl-4-ethylbenzoate 8b were obtained; these steroids inhibited only the 5 alpha-reductase type 2 enzyme. Finasteride and steroids 4, 5, 7b, 8a showed a comparable in vivo pharmacological activity, however the IC(50) values of these compounds were higher as compared to that of finasteride. These results indicated also that steroids 4, 5, 7a, and 7b bind to the androgen receptor whereas compounds 6, 8a and 8b failed to do so. The overall data from this study showed that steroids 5 and 7b bind to the AR and decreased of the growth of prostate and seminal vesicles. Moreover, 4 decreased also the growth of seminal vesicles.
Asunto(s)
3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , Progesterona/análogos & derivados , Progesterona/metabolismo , Receptores Androgénicos/metabolismo , Inhibidores de 5-alfa-Reductasa , Animales , Unión Competitiva , Cricetinae , Inhibidores Enzimáticos/farmacología , Finasterida/metabolismo , Finasterida/farmacología , Humanos , Isoenzimas/antagonistas & inhibidores , Isoenzimas/metabolismo , Cinética , Masculino , Mesocricetus , Persona de Mediana Edad , Estructura Molecular , Tamaño de los Órganos/efectos de los fármacos , Progesterona/farmacología , Próstata/efectos de los fármacos , Próstata/enzimología , Próstata/crecimiento & desarrollo , Unión Proteica , Vesículas Seminales/efectos de los fármacos , Vesículas Seminales/crecimiento & desarrolloRESUMEN
We investigated the effects of hydrocortisone during the prenatal period and its repercussion on puberty installation and adrenergic response of seminal vesicle in adult rats. The efficacy of the hydrocortisone treatment in reducing adrenal wet weight immediately after delivery in both the treated mothers and respective pups at birth may indicate impairment of the hypothalamus--pituitary--adrenal axis. This parameter was unchanged in the adult phase of these descendants, suggesting recuperation of this axis. In addition, the treatment with hydrocortisone delayed the age of puberty installation, probably by absence of both physiologic production and liberation of luteinizing hormone and testosterone. Despite the significant reduction in testosterone level as well as of wet weights of both vas deferens and testis in the adult phase, no difference was observed in the sensitivity of the seminal vesicle to the studied sympathetic agonist. However, the observed reduction in contractile response of the seminal vesicle may be a consequence of contractile-system damage in this organ. It is possible that this alteration may cause a reduction in the amount of vesicular secretion so important in the process of ejaculation. In conclusion, these results suggest that administration of hydrocortisone in late prenatal life did not influence the hypothalamus--pituitary--adrenal axis in adult life, although it altered the hypothalamus--pituitary--gonadal axis, and reduced testosterone production starting at puberty, as a consequence of an incomplete masculinization of the hypothalamus plus a reduction in the contractile response of the seminal vesicle.
Asunto(s)
Hidrocortisona/farmacología , Vesículas Seminales/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacos , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/crecimiento & desarrollo , Animales , Peso Corporal/efectos de los fármacos , Epinefrina/farmacología , Femenino , Genitales Masculinos/anatomía & histología , Genitales Masculinos/crecimiento & desarrollo , Masculino , Norepinefrina/farmacología , Tamaño de los Órganos/efectos de los fármacos , Fenilefrina/farmacología , Embarazo , Efectos Tardíos de la Exposición Prenatal , Ratas , Ratas Wistar , Vesículas Seminales/crecimiento & desarrollo , Vesículas Seminales/inervación , Testosterona/sangre , Vasoconstrictores/farmacología , Aumento de Peso/efectos de los fármacosRESUMEN
Previous studies in rats suggested that picrotoxin, a GABA(A) receptor antagonist, may cause long-term changes in male reproductive physiology and behavior in rats exposed during prenatal and postnatal periods. The present study has further examined this phenomenon. Wistar rat dams were dosed subcutaneously with 0.75 mg/kg picrotoxin in saline, or vehicle alone, during the perinatal period (day 19 of gestation, immediately after parturition, and once a day during the first 5 days of lactation). Birth weight and sexual maturation of pups were unchanged; however, plasma testosterone levels and sexual behavior was altered in male offspring. Although fertile, these males showed altered mating behavior in terms of a decrease in the mean number of mounts during a 30-min observation period with normal females. Some showed homosexual behavior when castrated and pretreated with exogenous estrogen. These findings suggest that perinatal exposure to picrotoxin alters sexual dimorphism in the developing rat brain, manifesting as altered reproductive performance and sexual behavior of males.
Asunto(s)
Antagonistas del GABA/toxicidad , Picrotoxina/toxicidad , Efectos Tardíos de la Exposición Prenatal , Conducta Sexual Animal/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Inyecciones Subcutáneas , Masculino , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Ratas , Ratas Wistar , Vesículas Seminales/efectos de los fármacos , Vesículas Seminales/crecimiento & desarrollo , Recuento de Espermatozoides , Testículo/efectos de los fármacos , Testículo/crecimiento & desarrolloRESUMEN
The effects of maternal exposure to fenvalerate during the prenatal and postnatal periods of sexual brain differentiation were studied in adult male offspring. Behavioral (open field, stereotyped, and sexual behaviors), physical (sexual maturation, body and organ weights), endocrine (testosterone levels), and neurochemical (striatal and hypothalamic monoamine and respective metabolite levels) data were assessed. The results showed that there was no change in the age of testis descent or testis weight, nor were there changes in monoamine levels or stereotyped behavior. However, there were significant reductions in ductus deferens and seminal vesicle weights and plasma testosterone concentrations. In addition, treated offspring showed decreased male sexual behavior and increased immobility in the open field. These results indicate that perinatal exposure to fenvalerate during the critical periods of male brain sexual differentiation has long-term effects on the reproductive physiology and behavior of male rats.
Asunto(s)
Insecticidas/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Piretrinas/efectos adversos , Animales , Conducta Animal/efectos de los fármacos , Monoaminas Biogénicas/metabolismo , Peso Corporal/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Sistema Endocrino/efectos de los fármacos , Femenino , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Locomoción/efectos de los fármacos , Masculino , Nitrilos , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Próstata/crecimiento & desarrollo , Ratas , Ratas Wistar , Vesículas Seminales/crecimiento & desarrollo , Caracteres Sexuales , Conducta Sexual Animal/efectos de los fármacos , Testosterona/sangre , Conducto Deferente/crecimiento & desarrolloRESUMEN
Norethisterone (NET), a 19-nor synthetic progestin, undergoes enzyme-mediated 5alpha-reduction and exerts potent androgenic effects in target organs. To investigate its mode of androgenic action we examined, in a comparative manner, the in vitro metabolism of NET and testosterone (T), as well as the binding affinities to androgen receptors (AR) and the androgenic potency of NET, T, and their 5alpha-reduced derivatives. Bioconversion of [3H]-NET and [3H]-T was studied in rat prostate homogenates, AR binding affinity was assessed in rat ventral prostates using [3H]-mibolerone as the radioligand, and the androgenic potency was evaluated by the increase of beta-glucuronidase activity in the mouse kidney, and by the growth of accessory sex organs in castrated male rats. The results demonstrated that 5alpha-NET displayed a higher AR binding affinity but a significantly lower androgenic potency than unchanged NET. The bioconversion studies indicated that the metabolism of NET was similar to that of T, although to a lesser extent, thus ruling out the possibility that the synthetic progestin metabolizes rapidly into less active derivatives. To investigate the nature of the paradoxical effect of 5alpha-reduction upon the NET molecule, the interaction with AR and the androgenic potency of T, 19-nortestosterone (19norT), 17alpha-ethynyl testosterone (ET) and their 5alpha-reduced derivatives were examined. The results of AR binding studies revealed that 5alpha-reduction of T and ET significantly enhanced their affinities, and that the 5alpha-derivative of 19norT displayed a similar binding affinity to that exhibited by 19norT. In terms of biological activity, the results showed that 5alpha-reduction of T and 19norT significantly increased their androgenic potency, whereas 5alpha-reduction of ET resulted in a significant diminution of its androgenicity in a manner similar to that observed with the 5alpha-reduction of NET. When NET and 19norT were simultaneously administered with 5alpha-dihydrotestosterone they exhibited a potent synandrogenic activity, an effect that was cancelled by their 5alpha-reduction. Interestingly, ET displayed an antiandrogenic activity, an effect that was also suppressed by its 5alpha-reduction. The overall results demonstrated a distinctive, paradoxical effect of 5alpha-reduction upon the NET molecule, which was different from that seen in naturally occurring androgens, and which suggests that the presence of the 17alpha-ethynyl group plays a key role in this phenomenon. The data provided further evidence that the metabolism of synthetic contraceptive progestins modulates the expression of their hormone-like actions.
Asunto(s)
Glucuronidasa/metabolismo , Noretindrona/metabolismo , Noretindrona/farmacología , Receptores Androgénicos/metabolismo , Andrógenos/fisiología , Animales , Unión Competitiva , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Etisterona/metabolismo , Etisterona/farmacología , Glucuronidasa/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Nandrolona/análogos & derivados , Nandrolona/metabolismo , Nandrolona/farmacología , Noretindrona/análogos & derivados , Orquiectomía , Tamaño de los Órganos/efectos de los fármacos , Oxidación-Reducción , Congéneres de la Progesterona/metabolismo , Próstata/efectos de los fármacos , Próstata/crecimiento & desarrollo , Próstata/metabolismo , Ratas , Ratas Wistar , Vesículas Seminales/efectos de los fármacos , Vesículas Seminales/crecimiento & desarrollo , Relación Estructura-Actividad , Testosterona/análogos & derivados , Testosterona/metabolismo , Testosterona/farmacología , TritioRESUMEN
1. The internal genital organs of prepubertal, 21-day old male Wistar rats were sympathectomized by ip injection of guanethidine (G), at doses of 5 mg/kg per day (N = 10) or 10 mg/kg per day (N = 10), for 20 days. Controls (N = 10) received saline. 2. Plasma testosterone level (measured by radioimmunoassay) decreased significantly in sympathectomized rats from 4.11 +/- 0.57 to 1.76 +/- 0.37 ng/ml (5 mg/kg G) and to 1.17 +/- 0.26 ng/ml (10 mg/kg G). Plasma levels of luteinizing and follicle-stimulating hormones and of prolactin were unaltered. 3. Chemical denervation caused a significant decrease in ventral prostate wet weight from 74.3 +/- 5.5 to 59.3 +/- 4.7 mg (5 mg/kg G) and to 54.6 +/- 4.1 mg (10 mg/kg G) and in seminal vesicle wet weight from 36.5 +/- 6.8 to 31.7 +/- 5.2 mg (5 mg/kg G) and to 21.3 +/- 1.6 mg (10 mg/kg G). 4. The potential secretory activity of the prostate (measured in terms of fructose content) decreased significantly in guanethidine-treated rats from 0.38 +/- 0.02 to 0.30 +/- 0.02 mg/g (5 mg/kg G) and to 0.20 +/- 0.02 mg/g (10 mg/kg G). The seminal vesicle fructose content (0.33 +/- 0.04 mg/g for controls), however, was not altered by chemical denervation. 5. Our data suggested that sympathetic neurons may be involved in the control of LH receptors, at least in the prepubertal phase of sexual development. They may also be directly related to growth and secretory activity of the male accessory sex glands.
Asunto(s)
Próstata/crecimiento & desarrollo , Vesículas Seminales/crecimiento & desarrollo , Simpatectomía Química , Animales , Guanetidina , Masculino , Tamaño de los Órganos , Próstata/metabolismo , Radioinmunoensayo , Ratas , Ratas Wistar , Testosterona/sangreRESUMEN
1. The internal genital organs of prepubertal, 21-day old male Wistar rats were sympathectomized by ip injection of guanethidine (G), at doses of 5 mg/kg per day (N = 10) or 10 mg/kg per day (N = 10), for 20 days. Controls (N = 10) received saline. 2. Plasma testosterone level (measured by radioimmunoassay) decreased significantly in sympathectomized rats from 4.11 +/- 0.57 to 1.76 +/- 0.37 ng/ml (5 mg/kg G) and to 1.17 +/- 0.26 ng/ml (10 mg/kg G). Plasma levels of luteinizing and follicle-stimulating hormones and of prolactin were unaltered. 3. Chemical denervation caused a significant decrease in ventral prostate wet weight from 74.3 +/- 5.5 to 59.3 +/- 4.7 mg (5 mg/kg G) and to 54.6 +/- 4.1 mg (10 mg/kg G) and in seminal vesicle wet weight from 36.5 +/- 6.8 to 31.7 +/- 5.2 mg (5 mg/kg G) and to 21.3 +/- 1.6 mg (10 mg/kg G). 4. The potential secretory activity of the prostate (measured in terms of fructose content) decreased significantly in guanethidine-treated rats from 0.38 +/- 0.02 to 0.30 +/- 0.02 mg/g (5 mg/kg G) and to 0.20 +/- 0.02 mg/g (10 mg/kg G). The seminal vesicle fructose content (0.33 +/- 0.04 mg/g for controls), however, was not altered by chemical denervation. 5. Our data suggested that sympathetic neurons may be involved in the control of LH receptors, at least in the prepubertal phase of sexual development. They may also be directly related to growth and secretory activity of the male accessory sex glands
Asunto(s)
Animales , Masculino , Ratas , Próstata/crecimiento & desarrollo , Simpatectomía Química , Vesículas Seminales/crecimiento & desarrollo , Guanetidina , Tamaño de los Órganos , Próstata , Radioinmunoensayo , Ratas Wistar , Testosterona/sangreRESUMEN
Age changes in the structure of the seminal vesicles and in the rate of production of fructose and citric acid have been studied in a Brazilian (Nelore) zebu, from the fetal period to 36 months of age. At 3 and 6 months, the microscopic anatomy of the gland resembled that of the fetus; the tubules of the seminal vesicles had a reduced diameter and a low epithelial layer; only a few presented traces of secretion, and tissue contents of fructose and citric acid were accordingly low. At 12 months, the tubules were more ramified and had a larger diameter. In the 18-month-old animals the seminal vesicles presented substantial modifications; the tubules were large, with irregular lumina and surrounded by narrow stroma, the epithelial layer was higher than that of previous stages and its columnar cells had nuclei located basally. Tissue levels of fructose increased rapidly between 12 and 18 months. At 24 months, the seminal vesicles had reached the adult condition characterized by intense proliferation of tubules with irregular lumina and abundant secretory material. Numerous dark columnar cells were found in the epithelium. Seminal vesicles of Nelore zebus contain less fructose and citric acid than those of taurine bulls of comparable age.