RESUMEN
Long-term use of anabolic androgenic steroids (AAS) in supratherapeutic doses is associated with severe adverse effects, including physical, mental, and behavioral alterations. When used for recreational purposes several AAS are often combined, and in scientific studies of the physiological impact of AAS either a single compound or a cocktail of several steroids is often used. Because of this, steroid-specific effects have been difficult to define and are not fully elucidated. The present study used male Wistar rats to evaluate potential somatic and behavioral effects of three different AAS; the decanoate esters of nandrolone, testosterone, and trenbolone. The rats were exposed to 15 mg/kg of nandrolone decanoate, testosterone decanoate, or trenbolone decanoate every third day for 24 days. Body weight gain and organ weights (thymus, liver, kidney, testis, and heart) were measured together with the corticosterone plasma levels. Behavioral effects were studied in the novel object recognition-test (NOR-test) and the multivariate concentric square field-test (MCSF-test). The results conclude that nandrolone decanoate, but neither testosterone decanoate nor trenbolone decanoate, caused impaired recognition memory in the NOR-test, indicating an altered cognitive function. The behavioral profile and stress hormone level of the rats were not affected by the AAS treatments. Furthermore, the study revealed diverse AAS-induced somatic effects i.e., reduced body weight development and changes in organ weights. Of the three AAS included in the study, nandrolone decanoate was identified to cause the most prominent impact on the male rat, as it affected body weight development, the weights of multiple organs, and caused an impaired memory function.
Asunto(s)
Anabolizantes , Trastornos de la Memoria , Nandrolona , Ratas Wistar , Testosterona , Animales , Masculino , Testosterona/sangre , Testosterona/análogos & derivados , Ratas , Nandrolona/análogos & derivados , Nandrolona/farmacología , Anabolizantes/efectos adversos , Anabolizantes/farmacología , Trastornos de la Memoria/inducido químicamente , Tamaño de los Órganos/efectos de los fármacos , Acetato de Trembolona/farmacología , Nandrolona Decanoato/farmacología , Peso Corporal/efectos de los fármacos , Corticosterona/sangre , Reconocimiento en Psicología/efectos de los fármacosRESUMEN
The present study aimed to evaluate whether primed anoestrus mares are suitable recipients for embryos produced by intracytoplasmic sperm injection (ICSI). Anoestrus was confirmed in four mares and daily doses of oestradiol benzoate (6 mg in total) over 5 days were administered; after 3 days of rest, oral altrenogest was administered at 0.088 mg/kg and embryos (1 to 5 embryos per mare; 15 in total) were transferred 3.5 days after progesterone onset. Uterine lavage was conducted 48 h after transfer. The results revealed an 80% embryo recovery rate, and among the retrieved embryos, 67% showed evident intrauterine development. Hence, ICSI-derived embryos can be successfully transferred to primed anoestrus mares, but more studies are required to ensure further embryo development and foaling.
Asunto(s)
Anestro , Transferencia de Embrión , Estradiol , Inyecciones de Esperma Intracitoplasmáticas , Acetato de Trembolona , Animales , Caballos/embriología , Femenino , Estradiol/farmacología , Estradiol/análogos & derivados , Estradiol/administración & dosificación , Transferencia de Embrión/veterinaria , Inyecciones de Esperma Intracitoplasmáticas/veterinaria , Anestro/efectos de los fármacos , Acetato de Trembolona/análogos & derivados , Acetato de Trembolona/farmacología , Acetato de Trembolona/administración & dosificación , Embarazo , Desarrollo Embrionario/efectos de los fármacos , Progesterona/farmacologíaRESUMEN
Mechanisms in the brain controlling secretion of gonadotropin hormones in pigs, particularly luteinizing hormone (LH), are poorly understood. Kisspeptin is a potent LH stimulant that is essential for fertility in many species, including pigs. Neurokinin B (NKB) acting through neurokinin 3 receptor (NK3R) is involved in kisspeptin-stimulated LH release, but organization of NKB and NK3R within the porcine hypothalamus is unknown. Hypothalamic tissue from ovariectomized (OVX) gilts was used to determine the distribution of immunoreactive kisspeptin, NKB, and NK3R cells in the arcuate nucleus (ARC). Almost all kisspeptin neurons coexpressed NKB in the porcine ARC. Immunostaining for NK3R was distributed throughout the preoptic area (POA) and in several hypothalamic areas including the periventricular and retrochiasmatic areas but was not detected within the ARC. There was no colocalization of NK3R with gonadotropin-releasing hormone (GnRH), but NK3R-positive fibers in the POA were in close apposition to GnRH neurons. Treating OVX gilts with the progestin altrenogest decreased LH pulse frequency and reduced mean circulating concentrations of LH compared with OVX control gilts (P < 0.01), but the number of kisspeptin and NKB cells in the ARC did not differ between treatments. The neuroanatomical arrangement of kisspeptin, NKB, and NK3R within the porcine hypothalamus confirms they are positioned to stimulate GnRH and LH secretion in gilts, though differences with other species exist. Altrenogest suppression of LH secretion in the OVX gilt does not appear to involve decreased peptide expression of kisspeptin or NKB.
Asunto(s)
Hipotálamo/metabolismo , Kisspeptinas/genética , Neuroquinina B/genética , Progestinas/farmacología , Receptores de Neuroquinina-3/genética , Sus scrofa/genética , Acetato de Trembolona/análogos & derivados , Animales , Femenino , Perfilación de la Expresión Génica/veterinaria , Hipotálamo/efectos de los fármacos , Kisspeptinas/metabolismo , Neuroquinina B/metabolismo , Receptores de Neuroquinina-3/metabolismo , Sus scrofa/metabolismo , Acetato de Trembolona/farmacologíaRESUMEN
BACKGROUND: The present study investigated whether the administration of the progestin altrenogest provides noninvasive, temporary, and reversible suppression of gonadal function in the goat as a potential alternative to chirurgical castration, which is related with irreversibility, risks of complications till death of the animal and welfare issues. Eight sexually mature Peacock goats were randomly divided into two groups. The experimental group was administered altrenogest (0.088 mg/kg) orally once daily for 7 weeks. The remaining four goats received an oral glucose solution and served as the control group. After completing the administration period, the reversibility of the medication was evaluated for another 7 weeks (observation phase). The treatment effects were assessed by clinical examination; ultrasound examination of the testes, including one-dimensional grayscale analysis, blood testosterone levels, analysis of semen parameters and libido. At the end of the observation period, the animals were castrated and the testicles were examined histologically. RESULTS: Altrenogest treatment had no significant effect on the physical development of the goats, the sonographic appearance of the testes, the gray values measured in the ultrasound images, or the blood testosterone levels. The effects of treatment on the testicular and semen parameters varied widely in the experimental animals; the testicle volume was significantly lower and the number of pathologically altered sperm in the ejaculate was significantly higher in treated animals. CONCLUSION: These findings indicate that daily altrenogest administration at a dose of 0.088 mg/kg does not reliably suppress gonadal function in the goat.
Asunto(s)
Anticonceptivos Masculinos/farmacología , Cabras , Testículo/efectos de los fármacos , Acetato de Trembolona/análogos & derivados , Administración Oral , Animales , Anticonceptivos Masculinos/administración & dosificación , Masculino , Análisis de Semen/veterinaria , Conducta Sexual Animal/efectos de los fármacos , Testículo/diagnóstico por imagen , Testosterona/sangre , Acetato de Trembolona/administración & dosificación , Acetato de Trembolona/farmacologíaRESUMEN
A synthetic progestin altrenogest (ALT) is used to synchronize the estrus cycle of swine for fixed-time artificial insemination (AI) and has been shown to improve follicular development and reproductive performances in post-weaning sows. However, the effects of ALT treatment on reproductive tracts, including the ovaries, oviducts and uterus have not been yet clarified. In this study, we examined the expression of genes involved in endometrial responses in ALT-treated sows. ALT did not significantly alter luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol profiles in blood compared to untreated control. Quantitative RT-polymerase chain reaction (qRT-PCR) analysis showed that the expression of genes encoding galectin-3 (LGALS3) and fibroblast growth factor 9 (FGF9) was upregulated in the reproductive tracts of ALT-treated sows, including the ovaries, oviducts and uteri. Moreover, ALT treatment induced the expression of FGF9 and galectin-3 proteins, and promoted their localization to the luminal epithelium of the oviducts and uterus. Our findings suggest that the enhancement of reproductive performance shown by ALT-treated sows is associated with the upregulation of galectin-3 and FGF9, which are essential for endometrial receptivity, successful implantation, and pregnancy.
Asunto(s)
Factor 9 de Crecimiento de Fibroblastos , Galectina 3 , Porcinos/genética , Acetato de Trembolona , Animales , Femenino , Factor 9 de Crecimiento de Fibroblastos/metabolismo , Hormona Folículo Estimulante , Galectina 3/metabolismo , Inseminación Artificial/veterinaria , Ovario/efectos de los fármacos , Ovario/metabolismo , Oviductos/efectos de los fármacos , Oviductos/metabolismo , Embarazo , Acetato de Trembolona/análogos & derivados , Acetato de Trembolona/farmacología , Útero/efectos de los fármacos , Útero/metabolismoRESUMEN
For successful batch farrowing, porcine oestrus and ovulation must be synchronized using fixed-time artificial insemination (FTAI). However, exogenous gonadotropins, which are currently used in FTAI, negatively affect gilt ovulation. Here, we aimed to improve sexually mature gilt superovulation efficiency using passive immunization against inhibin during FTAI. Altrenogest-treated gilts were challenged with 10 ml anti-inhibin serum (AIS group, n = 6), 1,000 IU pregnant mare serum gonadotropin (PMSG group, n = 6), or 10 ml goat serum (control group, n = 6). Gilts in the AIS and PMSG groups were inseminated according to the FTAI protocol, and gilts in the control group were inseminated during natural oestrus. When PMSG was replaced by AIS during FTAI of gilts, ovulation rate and embryos recovered were significantly greater in the AIS group as compared to the other two groups (p < .05). Especially the average number of 6-8-cell embryos in the AIS group was significantly higher than that in the PMSG group (p < .01). Moreover, the blastocyst number in the AIS group was significantly higher than that in the PMSG group and the control group (p < .05). But there was no significant difference in the blastocyst number between the PMSG group and the control group (p > .05). Besides, plasma levels of estradiol-ß (E2) and progesterone (P4) were significantly greater in the AIS group as compared to the other two groups on Day 23 and D 27, respectively (p < .01). In summary, we devised an improved high-yield FTAI protocol for sexually mature gilts using AIS; this protocol had a greater superovulation efficiency than the FTAI using PMSG.
Asunto(s)
Inhibinas/antagonistas & inhibidores , Inseminación Artificial/veterinaria , Inducción de la Ovulación/veterinaria , Animales , Estradiol/sangre , Femenino , Cabras , Inseminación Artificial/métodos , Masculino , Inducción de la Ovulación/métodos , Progesterona/sangre , Superovulación/efectos de los fármacos , Sus scrofa/fisiología , Acetato de Trembolona/análogos & derivados , Acetato de Trembolona/farmacologíaRESUMEN
OBJECTIVE: To assess outcomes and behavior changes associated with bilateral laparoscopic ovariectomies. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Fifty-one equids. METHODS: Medical records were evaluated from equid bilateral laparoscopic ovariectomies from January 2012 to October 2018 with a potential of 6 months follow-up. Follow-up information obtained by telephone interviews included behavior before and after surgery. Likelihood ratio chi-square tests and odds ratios (OR) with 95% CI were calculated where applicable, with statistical significance at p < .05. RESULTS: Bilateral ovariectomy was performed in 51 cases, with elective (no pathologic ovaries) ovariectomies performed in 41/51 cases. Occasional estrus-like behavior was observed postoperatively in 14/51 (27%) mares, but the behavior was mild and manageable in all cases. There was no age effect on outcome in all bilateral (p = .56) or elective only (p = .36) cases. In 37/41 (90%) elective cases, improvement was observed in the reason for presentation. Some response to altrenogest administration for behavior modification was observed preoperatively in 12/18 (67%) elective cases. Response to altrenogest was not associated with (p = .31) or able to predict a beneficial response to surgery (OR = 5.5; 95% CI = 0.38-78.57; p = .21). CONCLUSION: Response to altrenogest in elective cases may not predict behavioral outcome with ovariectomy. Occasional estrus-like behavior in mares postoperatively was not problematic for any owners. Bilateral ovariectomy is a viable treatment option for owners seeking to alleviate undesirable behavior in mares. CLINICAL SIGNIFICANCE: This study should aid veterinarians and horse owners in case selection for bilateral ovariectomy.
Asunto(s)
Caballos/cirugía , Ovariectomía/veterinaria , Animales , Conducta Animal , Femenino , Laparoscopía/veterinaria , Enfermedades del Ovario/cirugía , Enfermedades del Ovario/veterinaria , Ovariectomía/métodos , Periodo Posoperatorio , Progestinas/administración & dosificación , Progestinas/farmacología , Estudios Retrospectivos , Resultado del Tratamiento , Acetato de Trembolona/administración & dosificación , Acetato de Trembolona/análogos & derivados , Acetato de Trembolona/farmacologíaRESUMEN
Altrenogest with gonadotropins is commonly used to synchronize the estrous cycle, but it can also lead to follicular cyst formation, especially in prepubertal gilts. Here, we aimed to investigate how maturity and altrenogest treatment affect the development, endocrine milieu, and molecular control of ovarian follicles. Crossbred prepubertal and mature gilts were challenged or not (control) with altrenogest, and ovaries were collected in the morning on the first day of behavioral estrus. In prepubertal gilts, altrenogest decreased the percentage of primordial and atretic small follicles, but increased large antral follicles when compared with controls. In mature gilts, altrenogest reduced the percentage of primary follicles and elevated the total number of antral follicles. Maturity affected the estradiol level in the follicular fluid of preovulatory follicles, luteinizing hormone (LH)-stimulated cyclic adenosine monophosphate (cAMP) generation, and LH receptor messenger RNA (mRNA) expression in granulosa. Moreover, cytochrome P45017A1 (CYP17A1) mRNA levels in the theca layer were affected and correlated with follicular androstendione and estradiol concentration. Altrenogest negatively affected follicular fluid progesterone concentration and decreased levels of prostaglandin (PG) E2 in prepubertal gilts and PGF2alpha metabolite in mature gilts. LH-stimulated cAMP release in granulosa cells of mature gilts as well as human chorionic gonadotropin- and forskolin-induced cAMP were also affected. In addition, altrenogest downregulated CYP17A1 mRNA in the prepubertal theca layer and PGF2alpha synthase expression in the granulosa and theca layer of mature gilts. To the best of our knowledge, this is the first study to report multiple effects of maturity and altrenogest on the endocrine milieu and molecular regulations governing ovarian follicle development in gilts.
Asunto(s)
Folículo Ovárico/efectos de los fármacos , Progestinas/farmacología , Acetato de Trembolona/análogos & derivados , Animales , Gonadotropina Coriónica/farmacología , AMP Cíclico/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Dinoprostona/metabolismo , Estradiol/metabolismo , Femenino , Hormona Folículo Estimulante/farmacología , Líquido Folicular/metabolismo , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Hormona Luteinizante/farmacología , Folículo Ovárico/crecimiento & desarrollo , Folículo Ovárico/metabolismo , Progesterona/metabolismo , Receptores de HL/genética , Receptores de HL/metabolismo , Porcinos , Acetato de Trembolona/farmacologíaRESUMEN
This is the first time fecal prostaglandin F2α metabolite (PGFM) analysis and altrenogest were used to determine and maintain a pregnancy in a zoo-housed black-footed cat (BFC; Felis nigripes). The established pair had not produced offspring during the year since their arrival at Birmingham Zoo. Fecal samples were collected daily and analyzed by enzyme immunoassay for progestagen, estrogen metabolite, and PGFM concentrations. After a 4-mo separation, the pair was reintroduced, and breeding was reinitiated. Two pregnancies were suggested by sustained, elevated progestagen concentrations (mean >3 × baseline) but were confirmed by elevated PGFM concentrations (mean 4-25 × baseline) beginning about 1 mo after presumed or observed breeding. The first pregnancy was lost after â¼51 days, and altrenogest was administered (0.088 mg/kg/day) in order to help sustain the second pregnancy, which went to term, but the kitten did not survive. Ultrasonographic and radiographic evaluations of pregnancy were utilized during the second pregnancy to provide information on litter size.
Asunto(s)
Felis/fisiología , Preñez , Progestinas/farmacología , Acetato de Trembolona/análogos & derivados , Animales , Conservación de los Recursos Naturales , Femenino , Embarazo , Acetato de Trembolona/farmacologíaRESUMEN
Cheetah are induced ovulators, experiencing short, variable oestrogen waves year-round. Exogenous gonadotrophin administration induces ovulation, but success is variable and often improves if ovaries are quiescent. After affirming the presence of short-term oestrogenic waves, we examined the effect of the timing of administration of exogenous equine and human chorionic gonadotrophins (eCG-hCG) within the oestrogen concentration pattern on subsequent follicle development and oocyte and corpus luteum quality. We also investigated ovarian suppression using an oral progestin (Altrenogest, 7 days) and assessed whether Altrenogest moderated adrenal activity by reducing glucocorticoid metabolites. All cheetahs exhibited short (every ~7-10 days), sporadic, year-round increases in faecal oestradiol punctuated by unpredictable periods (4-10 weeks) of baseline oestradiol (anoestrous). Gonadotrophin (eCG-hCG) efficacy was not affected by oestradiol 'wave' pattern if administered ≥3 days after an oestrogen peak. Such cheetahs produced normative faecal progestagen patterns and higher numbers (P<0.06) of mature oocytes than females given gonadotrophins ≤2 days after an oestradiol peak. Altrenogest supplementation expanded the interval between oestradiol peaks to 12.9 days compared with 7.3 days without progestin pretreatment. Altrenogest-fed females excreted less (P<0.05) glucocorticoid metabolites than non-supplemented counterparts. Results show that Altrenogest is effective for suppressing follicular activity, may contribute to reduced glucocorticoid production and may result in more effective ovulation induction via gonadotrophin therapy.
Asunto(s)
Estradiol/sangre , Ovario/efectos de los fármacos , Inducción de la Ovulación/veterinaria , Ovulación/efectos de los fármacos , Progestinas/farmacología , Acetato de Trembolona/análogos & derivados , Acinonyx , Animales , Femenino , Oocitos/efectos de los fármacos , Oocitos/metabolismo , Ovario/metabolismo , Inducción de la Ovulación/métodos , Acetato de Trembolona/farmacologíaRESUMEN
The androgen-induced alterations in adult rodent skeletal muscle fibre cross-sectional area (fCSA), satellite cell content and myostatin (Mstn) were examined in 10-month-old Fisher 344 rats (n = 41) assigned to Sham surgery, orchiectomy (ORX), ORX + testosterone (TEST; 7.0 mg week-1 ) or ORX + trenbolone (TREN; 1.0 mg week-1 ). After 29 days, animals were euthanised and the levator ani/bulbocavernosus (LABC) muscle complex was harvested for analyses. LABC muscle fCSA was 102% and 94% higher in ORX + TEST and ORX + TREN compared to ORX (p < .001). ORX + TEST and ORX + TREN increased satellite cell numbers by 181% and 178% compared to ORX, respectively (p < .01), with no differences between conditions for myonuclear number per muscle fibre (p = .948). Mstn protein was increased 159% and 169% in the ORX + TEST and ORX + TREN compared to ORX (p < .01). pan-SMAD2/3 protein was ~30-50% greater in ORX compared to SHAM (p = .006), ORX + TEST (p = .037) and ORX + TREN (p = .043), although there were no between-treatment effects regarding phosphorylated SMAD2/3. Mstn, ActrIIb and Mighty mRNAs were lower in ORX, ORX + TEST and ORX + TREN compared to SHAM (p < .05). Testosterone and trenbolone administration increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Several genes and signalling proteins related to myostatin signalling were differentially regulated by ORX or androgen therapy.
Asunto(s)
Anabolizantes/farmacología , Andrógenos/farmacología , Músculo Esquelético/efectos de los fármacos , Miostatina/metabolismo , Células Satélite del Músculo Esquelético/efectos de los fármacos , Testosterona/farmacología , Acetato de Trembolona/farmacología , Receptores de Activinas Tipo II/metabolismo , Anabolizantes/administración & dosificación , Andrógenos/administración & dosificación , Animales , Recuento de Células , Diferenciación Celular/efectos de los fármacos , Aumento de la Célula/efectos de los fármacos , Masculino , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/metabolismo , Orquiectomía/efectos adversos , Ratas , Ratas Endogámicas F344 , Células Satélite del Músculo Esquelético/citología , Proteína Smad2/metabolismo , Proteína smad3/metabolismo , Testículo/cirugía , Testosterona/administración & dosificación , Acetato de Trembolona/administración & dosificaciónRESUMEN
The study aimed to assess whether altrenogest treatment, fed before weaning (from -8 to -2 days), could improve fertility of sows showing reproductive seasonality. Ninety sows (50 in winter-spring [WS] and 40 in summer-autumn [SA]) were randomly selected and assigned to control (C; 27 in WS and 20 in SA) or altrenogest treatment (A; 23 in WS and 20 in SA) groups. The diameter and number of ovarian follicles were transrectally scanned at the onset of oestrus. Oestrus was evaluated twice daily from weaning to day 8 post-weaning. Sows in oestrus were post-cervically inseminated at 0 and 24 hr after the onset of oestrus with liquid stored semen (1.5 × 109 sperm/doses), and farrowing rates (FR) and total piglets born (LS) were recorded. More (p < .01) sows showed no signs of oestrus within 8 days after weaning in SA (30%) than in WS (2%), without differences between A and C groups. The diameter (cm) of the follicles at the onset of oestrus was larger in A than in C sows (0.76 ± 0.01 vs 0.73 ± 0.01; p < .01), irrespective of the season. No differences in the number of follicles were found. FR did not differ between seasons and groups, being always above 85%. LS was larger (p < .01) in A (14.00 ± 0.46) than C (12.27 ± 0.44) sows, irrespective of the season. In conclusion, a short-term altrenogest treatment at the end of lactation improves the total number of piglets born from weaned sows, probably by promoting a better and more homogeneous follicular development at the start of oestrus.
Asunto(s)
Tamaño de la Camada , Folículo Ovárico/efectos de los fármacos , Progestinas/farmacología , Sus scrofa , Acetato de Trembolona/análogos & derivados , Animales , Estro/efectos de los fármacos , Femenino , Inseminación Artificial/veterinaria , Lactancia/fisiología , Masculino , Folículo Ovárico/fisiología , Embarazo , Progestinas/administración & dosificación , Acetato de Trembolona/farmacologíaRESUMEN
SUMMARY: In males, visceral obesity and androgen deficiency often present together and result in harmful effects on bone. Our findings show that both factors are independently associated with adverse effects on femoral bone structure and strength, and trenbolone protects rats from diet-induced visceral obesity and consequently normalises femoral bone structural strength. INTRODUCTION: In light of the rapidly increasing incidence of obesity and osteoporosis globally, and recent conjecture regarding the effects of visceral adiposity and testosterone deficiency on bone health, we investigated the effects of increased visceral adipose tissue (VAT) mass on femoral bone mineral density (BMD), structure and strength in normal weight rats with testosterone deficiency. METHODS: Male Wistar rats (n = 50) were fed either standard rat chow (CTRL, n = 10) or a high-fat/high-sugar diet (HF/HS, n = 40). Following 8 weeks of feeding, rats underwent sham surgery (CTRL, n = 10; HF/HS, n = 10) or orchiectomy (HF/HS + ORX, n = 30). Following a 4-week recovery period, mini-osmotic pumps containing either vehicle (CTRL, n = 10; HF/HS, n = 10; HF/HS + ORX, n = 10), 2.0 mg kg day(-1), testosterone (HF/HS + ORX + TEST, n = 10) or 2.0 mg kg day(-1) trenbolone (HF/HS + ORX + TREN, n = 10) were implanted for 8 weeks of treatment. Dual-energy X-ray absorptiometry and three-point bending tests were used to assess bone mass, structure and strength of femora. RESULTS: Diet-induced visceral obesity resulted in decreased bone mineral area (BMA) and content (BMC) and impaired femoral stiffness and strength. Orchiectomy further impaired BMA, BMC and BMD and reduced energy to failure in viscerally obese animals. Both TEST and TREN treatment restored BMA, BMC, BMD and energy to failure. Only TREN reduced visceral adiposity and improved femoral stiffness and strength. CONCLUSIONS: Findings support a role for both visceral adiposity and testosterone deficiency as independent risk factors for femoral osteoporosis, adverse bone geometry and impaired bone strength in male rats. Trenbolone may be a more effective candidate for androgen replacement therapy than testosterone in viscerally obese testosterone-deficient males.
Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Fémur/efectos de los fármacos , Obesidad Abdominal/complicaciones , Osteoporosis/prevención & control , Testosterona/deficiencia , Acetato de Trembolona/uso terapéutico , Absorciometría de Fotón/métodos , Anabolizantes/farmacología , Anabolizantes/uso terapéutico , Fenómenos Fisiológicos Nutricionales de los Animales/fisiología , Animales , Fenómenos Biomecánicos , Composición Corporal/fisiología , Densidad Ósea/efectos de los fármacos , Densidad Ósea/fisiología , Conservadores de la Densidad Ósea/farmacología , Dieta , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos/métodos , Fémur/fisiopatología , Masculino , Obesidad Abdominal/fisiopatología , Orquiectomía , Osteoporosis/etiología , Osteoporosis/fisiopatología , Distribución Aleatoria , Ratas Wistar , Factores de Riesgo , Testosterona/sangre , Acetato de Trembolona/farmacologíaRESUMEN
In this study, an alternative purification method for human paraoxonase 1 (hPON1) enzyme was developed using two-step procedures, namely, ammonium sulfate precipitation and Sepharose-4B-L-tyrosine-3-aminophenantrene hydrophobic interaction chromatography. SDS-polyacrylamide gel electrophoresis of the enzyme indicates a single band with an apparent M(W) of 43 kDa. The enzyme was purified 219-fold with a final specific activity of 4,408,400 U/mg and a yield of 10%. Furthermore, we examined the in vitro effects of some anabolic compounds, such as zeranol, 17 ß-estradiol, diethylstilbestrol, oxytocin, and trenbolone on the enzyme activity to understand the better inhibitory properties of these molecules. The five anabolic compounds dose dependently decreased the activity of hPON1 with inhibition constants in the millimolar-micromolar range. The results show that these compounds exhibit inhibitory effects on hPON1 at low concentrations with IC50 values ranging from 0.064 to 16.900 µM.
Asunto(s)
Anabolizantes/farmacología , Arildialquilfosfatasa/aislamiento & purificación , Arildialquilfosfatasa/metabolismo , Anabolizantes/administración & dosificación , Arildialquilfosfatasa/antagonistas & inhibidores , Cromatografía en Agarosa/métodos , Electroforesis en Gel de Poliacrilamida/métodos , Estradiol/farmacología , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Concentración 50 Inhibidora , Oxitocina/farmacología , Acetato de Trembolona/farmacología , Tirosina/química , Zeranol/farmacologíaRESUMEN
Chemical pollution is a pervasive and insidious agent of environmental change. One class of chemical pollutant threatening ecosystems globally is the endocrine disrupting chemicals (EDCs). The capacity of EDCs to disrupt development and reproduction is well established, but their effects on behaviour have received far less attention. Here, we investigate the impact of a widespread androgenic EDC on reproductive behaviour in the guppy, Poecilia reticulata. We found that short-term exposure of male guppies to an environmentally relevant concentration of 17ß-trenbolone-a common environmental pollutant associated with livestock production-influenced the amount of male courtship and forced copulatory behaviour (sneaking) performed toward females, as well as the receptivity of females toward exposed males. Exposure to 17ß-trenbolone was also associated with greater male mass. However, no effect of female exposure to 17ß-trenbolone was detected on female reproductive behaviour, indicating sex-specific vulnerability at this dosage. Our study is the first to show altered male reproductive behaviour following exposure to an environmentally realistic concentration of 17ß-trenbolone, demonstrating the possibility of widespread disruption of mating systems of aquatic organisms by common agricultural contaminants.
Asunto(s)
Agricultura , Conducta Sexual Animal/efectos de los fármacos , Contaminantes Químicos del Agua/efectos adversos , Contaminación del Agua/efectos adversos , Andrógenos/análisis , Andrógenos/farmacología , Animales , Peso Corporal/efectos de los fármacos , Disruptores Endocrinos/efectos adversos , Femenino , Masculino , Pigmentación/efectos de los fármacos , Poecilia , Caracteres Sexuales , Acetato de Trembolona/análisis , Acetato de Trembolona/farmacologíaRESUMEN
This study investigated the endocrine background of follicle size changes during post-weaning altrenogest treatment. altrenogest-treated sows received a 20-mg dosage daily at 8.00 a.m. from Day -1 to Day 14 after weaning. On Day -1, only 3/13 altrenogest-treated sows showed LH pulses compared with 8/8 control sows (P=0.001). On Day 0, control sows showed a typical high frequency-low amplitude LH pattern, indicative for recruitment of oestrogenic follicles. In altrenogest-treated animals on Day 0, half of the sows showed high frequency-high amplitude pulses from 4-5h after weaning. In altrenogest-treated sows, average follicle size increased from 3.1±0.5 mm on Day 0 to 4.4±0.6mm on Day 5, then decreased to 3.7±0.5 mm on Day 7 and stabilised thereafter. FSH and oestradiol (E2) concentrations showed a distinct diurnal pattern; high at 7.00 a.m. and low at 3.00 p.m. E2 concentrations (7.00 a.m.) showed a 2.5-fold increase from Day -1 to Day 2, and subsequently a 2-fold decline to reach a plateau at Day 8. FSH concentrations reached maximum levels by Day 5 and slowly declined afterwards. In conclusion, once-daily administration of altrenogest starting one day before weaning delays the weaning-induced increase in LH pulses. Although FSH and follicle size increase until Day 5 after weaning, follicle E2 production already decreased from Day 2 after weaning. Post-weaning altrenogest treatment thus results in a follicular wave of follicles that lose oestrogenic competence at Day 2 after weaning, presumably related to the changed LH dynamics during altrenogest treatment.
Asunto(s)
Estradiol/metabolismo , Hormona Folículo Estimulante/metabolismo , Hormona Luteinizante/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Sus scrofa/metabolismo , Acetato de Trembolona/análogos & derivados , Factores de Edad , Animales , Femenino , Modelos Lineales , Tamaño de los Órganos/fisiología , Folículo Ovárico/citología , Acetato de Trembolona/administración & dosificación , Acetato de Trembolona/farmacologíaRESUMEN
Androgen receptors (ARs) mediate the physiological effects of androgens in vertebrates. In fishes, AR-mediated pathways can be modulated by aquatic contaminants, resulting in the masculinisation of female fish or diminished secondary sex characteristics in males. The Murray-Darling rainbowfish (Melanotaenia fluviatilis) is a small-bodied freshwater teleost used in Australia as a test species for environmental toxicology research. We determined concentration-response profiles for selected agonists and antagonists of rainbowfish ARα and ARß using transient transactivation assays. For both ARα and ARß, the order of potency of natural agonists was 11-ketotestosterone (11-KT)>5α-dihydrotestosterone>testosterone>androstenedione. Methyltestosterone was a highly potent agonist of both receptors relative to 11-KT. The relative potency of the veterinary growth-promoting androgen, 17ß-trenbolone, varied by more than a factor of 5 between ARα and ARß. The non-steroidal anti-androgen bicalutamide exhibited high inhibitory potency relative to the structurally related model anti-androgen, flutamide. The inhibitory potency of the agricultural fungicide, vinclozolin, was approximately 1.7-fold relative to flutamide for ARα, but over 20-fold in the case of ARß. Fluorescent protein tagging of ARs showed that the rainbowfish ARα subtype is constitutively localised to the nucleus, while ARß is cytoplasmic in the absence of ligand, an observation which agrees with the reported subcellular localisation of AR subtypes from other teleost species. Collectively, these data suggest that M. fluviatilis ARα and ARß respond differently to environmental AR modulators and that in vivo sensitivity to contaminants may depend on the tissue distribution of the AR subtypes at the time of exposure.
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Antagonistas de Andrógenos/farmacología , Peces/metabolismo , Receptores Androgénicos/química , Receptores Androgénicos/metabolismo , Andrógenos/metabolismo , Animales , Australia , Femenino , Masculino , Microscopía Fluorescente , Oxazoles/farmacología , Filogenia , Isoformas de Proteínas , Especificidad por Sustrato , Activación Transcripcional , Acetato de Trembolona/farmacología , VirilismoRESUMEN
A captive Indochinese sika deer (Cervus nippon pseudaxis) was castrated at the age of 5 yr. The resultant abnormal antler growth over the next few years became difficult to manage from both the veterinary and husbandry standpoints. Using a commercially available trenbolone acetate and estradiol implant marketed for domestic cattle heifers, normal mineralization of the abnormal antlers was achieved along with the expected normal casting. The deer was then maintained for 6 yr using an annual implant regimen.
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Cuernos de Venado/efectos de los fármacos , Ciervos/fisiología , Estradiol/farmacología , Acetato de Trembolona/farmacología , Animales , Cuernos de Venado/crecimiento & desarrollo , Combinación de Medicamentos , Implantes de Medicamentos , Estradiol/administración & dosificación , Masculino , Orquiectomía/veterinaria , Acetato de Trembolona/administración & dosificaciónRESUMEN
BACKGROUND: The earlier onset of puberty seen in young American girls has led researchers to question if a causal relation exists between dietary sources of estrogenic compounds and precocious puberty. OBJECTIVE: Using the prepubertal gilt (young female pig) as an animal model, our hypothesis is that feeding beef obtained from cattle receiving growth-promoting steroidal implants postweaning does not alter the onset of puberty or the peripubertal body composition of gilts compared with contemporaries fed nonimplanted "natural" beef or a common meat alternative, tofu. METHOD: The base diet was formulated using canola meal replacing soybean meal to reduce diet estrogenicity. Feed intake was monitored and controlled to ensure similar intake. Gilts were assigned to treatments based on dam and initial body weight (mean: 24.5 ± 3.20 kg) at 61 d of age. The negative control base diet was supplemented with daily feedings of a cooked patty from nonimplanted steers (natural), from steers that had been treated with growth promotants [100 mg trenbolone acetate and 14 mg estradiol (E2) benzoate; implanted], or cooked tofu patty. RESULTS: E2 equivalents (nanogram per kilogram, as fed as analyzed by E-Screen) of the tofu (a soy-based product) supplement were â¼570 times the natural and â¼170 times the implanted supplements. There were no observed differences across treatments in live weight gain (P = 0.90), longissimus muscle area developed at the 10th and 11th rib interface (P = 0.46), and subcutaneous fat deposition (P = 0.41) at the same location over time or in the number of days to reach estrus (P = 0.55). CONCLUSIONS: Consumption of beef from growth implanted or natural steers or tofu at levels similar to those typically consumed by humans did not impact growth or onset of estrus in these prepubertal gilts.
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Estradiol/farmacología , Estro/efectos de los fármacos , Carne/análisis , Maduración Sexual/efectos de los fármacos , Porcinos/fisiología , Acetato de Trembolona/farmacología , Alimentación Animal/análisis , Animales , Bovinos , Estradiol/química , Femenino , Análisis de los Alimentos , Masculino , Alimentos de Soja/análisis , Acetato de Trembolona/químicaRESUMEN
Trenbolone acetate, a synthetic androgen, has been used as a growth promoter in beef cattle in the US since 1987. While several teleost studies have investigated the masculinization effects of the metabolite 17ß-trenbolone, few have focused on the reproductive impacts of all three trenbolone acetate (TBA) metabolites including trendione. Adult female medaka (Oryzias latipes) were exposed to TBA metabolites (10, 100, and 1000ng/L) for 14days (n=3). Histological examination revealed that TBA metabolites (1000ng/L) significantly reduced the percentage of primary ovarian follicles and increased the percentage of vitellogenic follicles compared to control fish. 17α-Trenbolone significantly increased whereas trendione reduced whole body levels of estradiol-17ß. Testosterone was significantly reduced by trendione treatment and only the highest dose of 17ß-trenbolone and lowest dose of trendione altered 11-ketotestosterone. Additionally, TBA metabolites may be further broken down and/or metabolized or converted by the animal influencing both sex steroid levels and ovarian development.