RESUMEN

The study aimed to investigate the repercussions of androgen modulation on the adrenal cortex of male gerbils, focusing on the morphophysiology, proliferation, and cell death, as well as the expression of hormone receptors and steroidogenic enzymes. Mongolian gerbils (Meriones unguiculatus) were divided into three experimental groups: Control (C), Testosterone (T), animals received injections of testosterone cypionate and Castrated (Ct), animals underwent orchiectomy. The results showed that castration increased the zona fasciculata and promoted cell hypertrophy in all zones. Testosterone supplementation increased cell proliferation and cell death. Androgen modulation promoted an increase in AR, Erα, and ERß. Castration promoted an increase in the CYP19, while decreasing 17ßHSD enzymes. Testosterone supplementation, on the other hand, reduced CYP17 and increased CYP19 and 3ßHSD enzymes. By analyzing the effects of androgen supplementation and deprivation, it can be concluded that testosterone is responsible for tissue remodeling in the cortex, regulating the rate of cell proliferation and death, as well as cell hypertrophy. Testosterone also modulate steroid hormone receptors and steroidogenic enzymes, consequently affecting the regulation, hormone synthesis and homeostasis of this endocrine gland.

Asunto(s)

Corteza Suprarrenal , Andrógenos , Proliferación Celular , Gerbillinae , Testosterona , Animales , Masculino , Testosterona/farmacología , Testosterona/metabolismo , Corteza Suprarrenal/efectos de los fármacos , Corteza Suprarrenal/metabolismo , Andrógenos/farmacología , Andrógenos/metabolismo , Proliferación Celular/efectos de los fármacos , Receptores Androgénicos/metabolismo , Orquiectomía , Esteroide 17-alfa-Hidroxilasa/metabolismo , Aromatasa/metabolismo , Muerte Celular/efectos de los fármacos

RESUMEN

For many years, it has been speculated that elevated testosterone levels may be critically involved in the genesis and proliferation of prostate cancer. METHODS: The effect of testosterone on the metabolic activity of hormone-independent [PC-3] and hormone-dependent [LNCAP] cancer cells was investigated in vitro. Additionally, the impact of testosterone nanoemulsion [nanocare®] on cell viability was accessed by flow cytometry. RESULTS: Despite the dependency of the normal prostate and of most prostatic cancers upon androgens, the obtained results indicate that, contrary to prevailing opinion, the supplementation of testosterone with higher doses in nanoemulsion was able to lower the metabolic activity and viability of prostate cancer cells. CONCLUSIONS: We conclude that the growth of hormone-independent and hormone-dependent prostate cancer cells was reduced by the exposure of a nanoemulsion of bioidentical testostosterone in vitro. To the best of our knowledge, this is the first time that the potential effect of a testosterone nanoemulsion on the metabolic activity of prostate cancer cells has been shown. Such tests suggest that the growth of hormone-independent and hormone-dependent prostate cancer cells was reduced by the administration of bioidentical testostosterone, and this might be an interesting strategy for prostate cancer treatment in diagnosed patients.

Asunto(s)

Supervivencia Celular , Emulsiones , Neoplasias de la Próstata , Testosterona , Humanos , Masculino , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/tratamiento farmacológico , Testosterona/farmacología , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Nanopartículas/química , Proliferación Celular/efectos de los fármacos , Células PC-3 , Andrógenos/farmacología

RESUMEN

Prior studies from others, performed in a different breed, reported that doe rabbits developing between two male siblings (2 M) during gestation display characteristics indicative of masculinization: larger anogenital distance (AGD), larger submandibular glands, and higher chinning frequency than females with zero (0 M) or one (1 M) contiguous brothers. Similar effects are provoked by injecting androgens to the pregnant doe suggesting that prenatal androgen exposure masculinizes female embryos. To further understand the scope of such masculinization we compared 0 M, 1 M, and 2 M females regarding behavioral, neuroendocrine, and somatic parameters, related or not to reproduction. IUP did not impact: body weight, sexual receptivity, mating-induced LH secretion, maternal nest-building, litter size, or milk output. At puberty: a) chinning frequency was: 0 M and males>1 M and 2 M; b) ambulation in open field was lowest in 1 M females and males. IUP effects on AGD were significant only on postnatal day 1: 0 M, 1 M, and males>2 M, in contrast to earlier study. Willingness to nurse at delivery was less frequent in 2 M than in 1 M and 0 M does and correlated with nursing occurrence across lactation. Does that did not nurse at parturition delivered fewer kits/min than those that nursed then, regardless of IUP. The duration of nursing bouts across lactation was significantly longer in the1 M and 2 M does that showed this behavior on postpartum days 1-20. Our findings indicate that IUP is associated with alterations in specific aspects of postpartum maternal behavior.

Asunto(s)

Reproducción , Maduración Sexual , Embarazo , Animales , Conejos , Femenino , Masculino , Parto , Lactancia , Andrógenos/farmacología , Peso Corporal

RESUMEN

OBJECTIVE: To analyze the effects of androgen therapy on the thyroarytenoid (TA) muscle, expression of androgen receptors (ARs) and hyaluronic acid (HA) concentration in the vocal folds (VFs) of adult female rats. METHODS: Twenty-one adult female Wistar rats were divided into experimental and control groups. The experimental group received weekly intramuscular injections of nandrolone decanoate for 9 weeks. Following euthanasia and dissection of the VFs, histomorphometric analysis of the TA muscle, immunohistochemical evaluation of ARs, and measurement of HA concentration using the ELISA-like fluorimetric method were performed. RESULTS: The experimental group exhibited a significantly larger mean fiber cross-sectional area in the TA muscle compared to the control group (434.3 ± 68.6 µm2 versus 305.7 ± 110.1 µm2; p = 0.029), indicating muscle hypertrophy. There was no significant difference in the number of muscle fibers. The experimental group showed higher expression of ARs in the lamina propria (62.0% ± 30.3% versus 22.0% ± 22.8%; p = 0.046) and in the TA muscle (45.0% ± 22.6% versus 18.3% ± 9.8%; p = 0.024). There was no significant difference in the concentration of HA. CONCLUSION: Exposure of adult female rats to androgen therapy resulted in hypertrophy of the TA muscle and increased expression of ARs in the VFs. The TA muscle seems to be the primary target of testosterone action in the VF, and the up-regulation of ARs might contribute to the persistent deepening of the voice. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2316-2321, 2024.

Asunto(s)

Músculos Laríngeos , Pliegues Vocales , Ratas , Femenino , Animales , Pliegues Vocales/fisiología , Testosterona/farmacología , Andrógenos/farmacología , Ratas Wistar , Membrana Mucosa , Hipertrofia

RESUMEN

The South American weakly electric fish, Gymnotus omarorum, displays territorial aggression year-round in both sexes. To examine the role of rapid androgen modulation in non-breeding aggression, we administered acetate cyproterone (CPA), a potent inhibitor of androgen receptors, to both male and females, just before staged agonistic interactions. Wild-caught fish were injected with CPA and, 30 min later, paired in intrasexual dyads. We then recorded the agonistic behavior which encompasses both locomotor displays and emission of social electric signals. We found that CPA had no discernible impact on the levels of aggression or the motivation to engage in aggressive behavior for either sex. However, CPA specifically decreased the expression of social electric signals in both males and female dyads. The effect was status-dependent as it only affected subordinate electrocommunication behavior, the emission of brief interruptions in their electric signaling ("offs"). This study is the first demonstration of a direct and rapid androgen effect mediated via androgen receptors on non-breeding aggression. Elucidating the mechanisms involved in non-breeding aggression in this teleost model allows us to better understand potentially conserved or convergent neuroendocrine mechanisms underlying aggression in vertebrates.

Asunto(s)

Pez Eléctrico , Gymnotiformes , Animales , Femenino , Masculino , Agresión , Receptores Androgénicos , Conducta Agonística , Andrógenos/farmacología

RESUMEN

The present study aimed to produce a monosex population of all male Nile tilapia (Oreochromis spp.) using 17α-methyl testosterone and common carp testes (as a source of natural androgen). Trial was conducted into two consecutive phases, the first was fry (4-5 days old)administration with negative control (without hormone) and positive control (with hormone) feed viz., MT1:60mg/kg, MT2:70mg/kg (17α-MT), carp testis CT1:70% and CT2:80% for 30 days to reverse the sex of male fish and the second phase was nursing the fingerlings for two months on control diet (32% Crude protein).Results revealed a significant growth rate (P<0.05) in the control group where final weight (4.8±0.34ab) and weight gained was recorded as 0.66±0.03ac. In proximate chemical composition of body meat, CT2 treatment showed maximum retention of crude protein, crude fat, and ash whereas dry matter showed maximum retention in MT2 and CT1 treatments. Morphological and histological examination revealed significant difference (p<0.05) in phenotypic males of Nile tilapia fed with the highest percent in MT-treated diet (MT2) of 95±0.58a while MT1, CT2 and CT1 had males of 85±6.0b, 70±5.0b and 65±6.5b, respectively. It was concluded that synthetic androgen (17αMT) was more effective for masculinization but natural androgen scan be an alternative method to produce male tilapia population in an environment-friendly manner as they are inexpensive, eco-friendly, and radially available. These results suggested that synthetic and natural androgen supplementation in the diet plays a significant role in improving growth performance and body composition.

Asunto(s)

Cíclidos , Tilapia , Animales , Masculino , Andrógenos/farmacología , Alimentación Animal/análisis , Dieta/veterinaria , Suplementos Dietéticos , Congéneres de la Testosterona

RESUMEN

BACKGROUND: Effective cancer treatment still challenges medicine since the strategies employed so far are not sufficiently safe and capable of specifically eliminating tumor cells. Prostate cancer (PCa) is a highly incident malignant neoplasm, and the outcome of patients, especially those with advanced castration-resistant PCa (CRPC), depends directly on the efficacy of the therapeutic agents, such as docetaxel (DOC). OBJECTIVES: This study investigated the synergistic potentiation of 4-nerolidylcatechol (4-NC) with DOC in inhibiting androgen-independent PCa cells. METHODS: The cytotoxic effect of 4-NC was evaluated against non-tumorigenic (RWPE-01) and PCa cell lines (LNCaP and PC-3), and the antiproliferative potential of 4-NC was assessed by flow cytometry and colony formation. The Chou-Talalay method was applied to detect the synergistic effect of 4-NC and DOC, and the mechanism of anticancer activities of this combination was investigated by analyzing players in epithelial-mesenchymal transition (EMT). RESULTS: 4-NC significantly reduced the viability of PC-3 cells in a dose-dependent manner, decreasing colony formation and proliferation. The combination of 4-NC and DOC was synergistic in the androgen-independent cells and allowed the reduction of DOC concentration, with increased cytotoxicity and induction of apoptosis when compared to compounds alone. Furthermore, when 4- NC was co-administered with DOC, higher expression levels of proteins associated with the epithelial phenotype were observed, controlling EMT in PC-3 cells. CONCLUSION: Collectively, these data demonstrated, for the first time, that the combination of 4-NC with reduced doses of DOC could be especially valuable in the suppression of oncogenic mechanisms of androgen-independent PCa cells.

Asunto(s)

Andrógenos , Neoplasias de la Próstata , Humanos , Masculino , Docetaxel/farmacología , Andrógenos/farmacología , Andrógenos/uso terapéutico , Taxoides/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Línea Celular Tumoral , Proliferación Celular

RESUMEN

BACKGROUND: The aim of this study was to evaluate modifications in proteoglycan morphology and composition in the prostatic stroma of 18-month-old gerbils after surgical castration, in association or not with an androgenic blockade. METHODS: The animals (n = 5) were sorted into groups subjected or not to antiandrogen treatment (flutamide 10 mg/kg/day) administered for the total postsurgery period and euthanized at 7- or 30-day postcastration; the control group consisted of intact animals. Tissue analysis included immunohistochemical assessment (perlecan and chondroitin sulfate) and proteoglycan morphology was analyzed by transmission electron microscopy. RESULTS: Chondroitin sulfate frequency was increased 7 days postcastration with an androgenic blockade. The presence of these carbohydrates was rare after 30 days of androgenic blockade treatment. There was a significant increase in the amount of perlecan in the prostate stroma from groups subjected to castration plus flutamide for 7 or 30 days. Ultrastructural analysis showed that the incidence of areas occupied by proteoglycans and basement membrane was altered by treatment. In addition, androgenic blockade results in changes in the amount, thickness, and morphology of these structures. At 30 days postcastration, with or without flutamide treatment, larger proteoglycans were common. CONCLUSIONS: In this study, in particular, the decrease in chondroitin sulfate after the longer period might be understood as a prostatic response to androgenic deprivation, while the high frequency and permanence of perlecan led to the assumption that its modulation could be androgen-independent. Length and form alterations in proteoglycans as well as associations among them and with the basement membrane were dynamic events in the prostate microenvironment.

Asunto(s)

Flutamida , Próstata , Masculino , Animales , Flutamida/farmacología , Gerbillinae , Andrógenos/farmacología , Sulfatos de Condroitina/farmacología , Orquiectomía

RESUMEN

Androgens are steroids that modulate various processes in the body, ranging from reproduction, metabolism, and even immune response. The main androgens are testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA). These steroids modulate the development and function of immune response cells. Androgens are generally attributed to immunosuppressive effects; however, this is not always the case. Variations in the concentrations of these hormones induce differences in the innate, humoral, and cell-mediated immune response, which is concentration dependent. The androgens at the highest concentration in the organism that bind to the androgen receptor (AR) are DHEA and testosterone. Therefore, in this work, we review the effects of DHEA and testosterone on the immune response. The main findings of this review are that DHEA and testosterone induce similar but also opposite effects on the immune response. Both steroids promote the activation of regulatory T cells, which suppresses the Th17-type response. However, while testosterone suppresses the inflammatory response, DHEA promotes it, and this modulation is important for understanding the involvement of androgens in infectious (bacterial, viral and parasitic) and autoimmune diseases, as well as in the sexual dimorphism that occurs in these diseases.

Asunto(s)

Deshidroepiandrosterona , Testosterona , Testosterona/farmacología , Testosterona/metabolismo , Deshidroepiandrosterona/farmacología , Andrógenos/farmacología , Dihidrotestosterona/farmacología , Dihidrotestosterona/metabolismo , Inmunidad Adaptativa

RESUMEN

Fetal or neonatal androgen exposure has a programming effect on ovarian function inducing a polycystic ovarian syndrome-like condition. Its effects on uterine structure and function are poorly studied. The aim of this work was to characterize the temporal course of changes in the rat uterine structure induced by neonatal exposure to aromatizable or not aromatizable androgens. Rats were daily treated with testosterone, dihydrotestosterone or vehicle during follicle assembly period (postnatal days 1 to 5). Uterine histoarchitecture, hormonal milieu, endometrial stromal collagen and capillary density were analyzed at prepubertal, pubertal and adult ages. Our data shows that neonatal androgen exposure induces early and long-lasting deleterious effects on uterine development, including altered adenogenesis and superficial epithelial alterations and suggest a role for altered serum estradiol levels in the maintenance and worsening of the situation. Our results suggest that alterations of the neonatal androgenic environment on the uterus could be responsible for alterations in the processes of implantation and maintenance of the embryo in women with polycystic ovary syndrome.

Asunto(s)

Andrógenos , Síndrome del Ovario Poliquístico , Humanos , Femenino , Ratas , Animales , Andrógenos/farmacología , Dihidrotestosterona/farmacología , Testosterona/farmacología , Síndrome del Ovario Poliquístico/inducido químicamente , Útero , Virilismo

RESUMEN

Prostate Cancer (PCa) is the second leading cause of cancer-related deaths among men worldwide. The treatment of advanced cases is based on chemotherapy, which lacks specificity and efficacy, due to severe side effects and resistance to the traditional drugs. Copper complexes have shown antitumoral efficacy and low toxicity, being considered a promising class of metal-based drugs for the treatment of malignant neoplasms. Thus, the present study aimed to evaluate the cellular effects of a copper(II) complex with 4-fluorophenoxyacetic acid hydrazide and 1,10-phenanthroline (1) on PCa cell lines, as well as the mutagenic/recombinogenic and anticarcinogenic potential of 1 in Drosophila melanogaster. PNT-2 (non-tumorigenic), LNCaP (hormone-responsive PCa) and PC-3 (androgen-independent PCa) cells were cultured, and cytotoxicity was assessed using the MTT assay. The expression levels of the proliferation markers Ki-67 and Cyclin D1 were analyzed by flow cytometry. Furthermore, the Somatic Mutation and Recombination Test (SMART) and the Epithelial Tumor Test (ETT) were performed. Complex 1 was selective to LNCaP cells, significantly reducing Ki-67 and Cyclin D1 expression levels. Sub-toxic concentrations of complex 1 were defined by the toxicity test in D. melanogaster, and no mutagenic/recombinogenic/carcinogenic effects were observed. Anticarcinogenic potential was observed in D. melanogaster, suggesting modulating activity of the complex 1 against Doxorubicin, a drug used as control by its carcinogenic properties. Therefore, complex 1 is a possible starting point for the development of new antitumor agents for the treatment of PCa.

Asunto(s)

Antineoplásicos , Neoplasias de la Próstata , Humanos , Masculino , Animales , Drosophila melanogaster , Cobre/farmacología , Ciclina D1 , Hidrazinas/farmacología , Andrógenos/farmacología , Antígeno Ki-67 , Neoplasias de la Próstata/patología , Mutágenos/farmacología , Carcinogénesis , Antineoplásicos/farmacología , Doxorrubicina/farmacología , Línea Celular Tumoral , Proteínas de Unión al ADN/farmacología

RESUMEN

Canine prostate cancer (PC) is an aggressive disease, and dogs can be considered comparative models for human PC. In recent years, canine PC has been shown to resemble human castrate-resistant prostate cancer. The influx and efflux of testosterone in prostatic luminal cells are regulated by P-glycoprotein (P-gp). Therefore, human PC generally lacks P-gp expression and maintains the expression of androgen receptors (ARs). However, this co-expression has not previously been investigated in dogs. Therefore, this study aimed to evaluate AR and P-gp co-expression to elucidate these protein patterns in canine prostate samples. We identified AR/P-gp double immunofluorescence co-expression of both proteins in normal luminal cells. However, in canine PC, cells lack AR expression and exhibit increased P-gp expression. These results were confirmed by gene expression analyses. Overall, our results strongly suggest that normal canine prostate testosterone influx may be regulated by P-gp expression, and that during progression to PC, prostatic cells lack AR expression and P-gp overexpress. P-gp expression in canine PC may be related to a phenotype of multiple drug resistance.

Asunto(s)

Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Andrógenos/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Animales , Perros , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Receptores Androgénicos/genética

RESUMEN

White adipose tissue (WAT) browning has gained interest due to its impact in obesity. Here, we evaluated the effect of androgens on the Ucp1-dependent thermogenic process from inguinal (IAT) and retroperitoneal (RPAT) WAT. Surgically androgens depleted rats (ODX) showed basal thermogenic activation (room temperature) in both WAT depots, which expressed higher levels of Ucp1, Prdm16 and Pgc1a. WAT pads from ODX cold-exposed rats (ODX-C) expressed increased levels of Ucp1 and Pgc1a and showed high UCP1 protein content. In primary beige adipocyte cultures, testosterone decreased the mitochondrial marker Cox8b and mitochondrial content. Finally, testosterone and dihydrotestosterone (DHT) decreased the expression of Ucp1, Pcg1a and Prdm16 in forskolin-stimulated beige adipocytes, an effect that was prevented by the antiandrogen flutamide. In conclusion, androgen deficient rats developed WAT depots with enhanced basal and cold-stimulated thermogenic activity. Additionally, in vitro androgen treatments inhibited the thermogenic program, effect which was mediated by the androgen receptor pathway.

Asunto(s)

Adipocitos Beige , Andrógenos , Adipocitos Beige/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Andrógenos/metabolismo , Andrógenos/farmacología , Animales , Frío , Ratas , Termogénesis/fisiología , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo

RESUMEN

Agonistic behavior governs the settlement of conflicts among conspecifics for limiting resources. Sex steroids play a critical role in the regulation of agonistic behavior which in turn may produce modulations in hormone titres. In this study we analyzed the association of androgens and estrogens with agonistic behavior in the annual fish Austrolebias reicherti. This native species inhabits temporary ponds that dry out completely during summer, having one of the shortest lifespans among vertebrates. They are highly sexually dimorphic and have a single breeding season during which they reproduce continuously. Here we measured plasma levels of 11-ketotestosterone (11KT) and 17ß-estradiol (E2) in adult males after the resolution of a social conflict and assessed the role of the aromatase conversion of testosterone (T) to E2 in male aggression. Winners had higher levels of 11KT than losers yet; winner 11KT levels did not differ from those of males not exposed to a social challenge. E2 levels did not show differences among winners, losers or control males. However, fights under the aromatase inhibitor Fadrozole were overall less aggressive than control fights. Our results suggest an androgen response to losing a conflict and that the conversion of T to E2 is involved in the regulation of aggressive behavior. Annual fish extreme life history may give new insights on hormone-behavior interactions.

Asunto(s)

Andrógenos , Ciprinodontiformes , Conducta Agonística , Andrógenos/farmacología , Animales , Estrógenos/farmacología , Estrógenos/fisiología , Hormonas Esteroides Gonadales , Masculino

RESUMEN

Cancer treatment frequently carries side effects, therefore, the search for new selective and effective molecules is indispensable. Hymenaea courbaril L. has been used in traditional medicine in South America to treat several diseases, including prostate cancer. Leaves' extracts from different polarities were evaluated using the 3-(4,5-methyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) cell viability assay to determine the cytotoxicity in prostate p53-null cells, followed by bio-guided fractionations to obtain the most cytotoxic fraction considering the selectivity index. The most cytotoxic fraction was analyzed by GC/MS to identify the active compounds. The majority compound, caryophyllene oxide, induced early and late apoptosis, depolarized the mitochondrial membrane, leading to several morphological changes and shifts in apoptotic proteins, and caspases were evidenced. Depolarization of the mitochondrial membrane releases the pro-apoptotic protein Bax from Bcl-xL. The apoptosis process is caspase-7 activation-dependent. Caryophyllene oxide is a safe anti-proliferative agent against PC-3 cells, inducing apoptosis with low toxicity towards normal cells.

Asunto(s)

Sesquiterpenos Policíclicos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Andrógenos/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Fabaceae/metabolismo , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Hymenaea/enzimología , Hymenaea/metabolismo , Masculino , Células PC-3 , Extractos Vegetales/farmacología , Hojas de la Planta/metabolismo , Sesquiterpenos Policíclicos/metabolismo , Próstata/efectos de los fármacos , Neoplasias de la Próstata/metabolismo

RESUMEN

Abstract To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.

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Resumo Investigar a concentração ideal de andrógenos em cultura de folículos pilosos de carneiro Hetiano e detectar os efeitos da concentração de andrógenos na proliferação e apoptose de células foliculares, por meio de imunofluorescência e de determinação quantitativa, em tempo real, da fluorescência dos níveis de expressão gênica de proteína associada à queratina. Folículos pilosos foram isolados por microdissecção, e folículos de lã e pedaços de pele foram cultivados em várias concentrações de di-hidrotestosterona (DHT) em meio de cultura. Em seguida, medições diárias de crescimento longitudinal dos folículos capilares foram obtidas usando um micrômetro microscópico. Folículos de lã cultivados de Hetianos foram corados pelo método SACPIC para revelar a estrutura do folículo piloso, enquanto fatias de pele de carneiro foram usadas para observar a proliferação celular por imunocoloração e apoptose celular por meio do método TUNEL. Em âmbito da biologia molecular, a expressão gênica da proteína associada à queratina (Kap) foi estudada usando folículos capilares cultivados por vários dias, in vitro. Os efeitos das concentrações de andrógenos no crescimento e desenvolvimento dos folículos de lã de Hetianos foram estudados experimentalmente. Ensaios de proliferação de EdU revelaram que o andrógeno promoveu a proliferação celular dentro das papilas dérmicas do folículo piloso. A detecção de apoptose por TUNEL demonstrou que o tratamento com andrógeno poderia atrasar a apoptose celular. Os resultados da reação em cadeia da polimerase transcrição reversa quantitativa (qPCR) demonstraram que os padrões de expressão gênica da proteína de enxofre Kap1.1, KIF1.2, Kap2.12 e Kap4.2 foram significativamente maiores no grupo de ovinos Hetianos de montanha. Uma concentração de androgênio de 100 nM pode promover o crescimento de células foliculares de lã de Hetianos in vitro, resultando na superexpressão de alguns genes da família Kap.

Asunto(s)

Animales , Lana , Queratinas/genética , Ovinos , Folículo Piloso , Andrógenos/farmacología

RESUMEN

To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.

Asunto(s)

Queratinas , Lana , Andrógenos/farmacología , Animales , Folículo Piloso , Queratinas/genética , Ovinos

RESUMEN

Synthetic androgens (male hormones) administered to fish nursery are being used in aquaculture to avoid sexual differentiation and unwanted spawning at the eggs or the first feeding fry stage of fish. Present trial was conducted with the aim to produce male common carp (Cyprinus carpio) by egg immersion technique. Through this little insight, the effect of different hormone concentrations (17α-methyltestosterone @ HC:150, 300, 450 and 600 µgl-1) with immersion times (IT: 24, 48 and 72 hrs) and their interaction effect (HC x IT) on the hatching percentage of Cyprinus carpio eggs, percent survival and percent of male's production was evaluated specifically. Results showed that egg hatching percentage decreased with increased IT likewise, survival of treated fry was affected by increasing the IT (P<0.001). The main interaction effect of HC x IT showed that the highest percent of male individuals (95%) was obtained at 450-600 µgl-1 HC for 72 hrs IT, followed by 88-92.50% at 150-300 µgl-1 HC for 72-hrsof IT, 87.50% at 48-hrs of IT for rest of the hormone treatments, and lowest 47.50% was recorded in control (P<0.05). Increased percent male of Cyprinus carpio was obtained with increasing HC across all ITs. It was observed that the immersion treatment at 600µgl-1 for 72 hours was more effective to change the sex ratio of pre hatch Cyprinus carpio. A comparative outlook made from this experimental trial that sex induction of Cyprinus carpio by eggs immersion using synthetic male steroid hormone is an alternative safe technique of fish sex reversal in contrast to oral administration of hormone in fish feed.

Asunto(s)

Carpas , Andrógenos/farmacología , Animales , Acuicultura , Inmersión , Masculino

RESUMEN

Hair follicle cyclical regeneration is regulated by epithelial-mesenchymal interactions. During androgenetic alopecia (AGA), hair follicle stem cells (HFSC) differentiation is impaired by deregulation of dermal papilla cells (DPC) secreted factors. We analyzed androgen influence on BMPs expression in DPC and their effect on HFSC differentiation to hair lineage. Androgens downregulated BMP2 and BMP4 in DPC spheroids. Addition of BMP2 restored alkaline phosphatase activity, marker of hair-inductivity in DPC, and DPC-induced HFSC differentiation, both inhibited by androgens. Concomitantly, in differentiating HFSC, an upregulation of BMPRIa and BMPRII receptors and nuclear ß-catenin accumulation, indicative of Wnt/ß-catenin pathway activation, were detected. Our results present BMP2 as an androgen-downregulated paracrine factor that contributes to DPC inductivity and favors DPC-induced HFSC differentiation to hair lineage, possibly through a crosstalk with Wnt/ß-catenin pathway. A comprehensive understanding of androgen-deregulated DPC factors and their effects on differentiating HFSC would help to improve treatments for AGA.

Asunto(s)

Andrógenos/farmacología , Proteína Morfogenética Ósea 2/genética , Diferenciación Celular , Dermis/citología , Regulación hacia Abajo/genética , Folículo Piloso/citología , Biomarcadores/metabolismo , Proteína Morfogenética Ósea 2/metabolismo , Proteína Morfogenética Ósea 4/metabolismo , Receptores de Proteínas Morfogenéticas Óseas/metabolismo , Diferenciación Celular/efectos de los fármacos , Línea Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Medios de Cultivo Condicionados/farmacología , Regulación hacia Abajo/efectos de los fármacos , Humanos , Ligandos , Transporte de Proteínas/efectos de los fármacos , Esferoides Celulares/citología , Esferoides Celulares/efectos de los fármacos , Células Madre/citología , Células Madre/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos , beta Catenina/metabolismo

RESUMEN

Synthetic androgens (male hormones) administered to fish nursery are being used in aquaculture to avoid sexual differentiation and unwanted spawning at the eggs or the first feeding fry stage of fish. Present trial was conducted with the aim to produce male common carp (Cyprinus carpio) by egg immersion technique. Through this little insight, the effect of different hormone concentrations (17α-methyltestosterone @ HC:150, 300, 450 and 600 µgl-1) with immersion times (IT: 24, 48 and 72 hrs) and their interaction effect (HC x IT) on the hatching percentage of Cyprinus carpio eggs, percent survival and percent of male's production was evaluated specifically. Results showed that egg hatching percentage decreased with increased IT likewise, survival of treated fry was affected by increasing the IT (P<0.001). The main interaction effect of HC x IT showed that the highest percent of male individuals (95%) was obtained at 450-600 µgl-1 HC for 72 hrs IT, followed by 88-92.50% at 150-300 µgl-1 HC for 72-hrsof IT, 87.50% at 48-hrs of IT for rest of the hormone treatments, and lowest 47.50% was recorded in control (P<0.05). Increased percent male of Cyprinus carpio was obtained with increasing HC across all ITs. It was observed that the immersion treatment at 600µgl-1 for 72 hours was more effective to change the sex ratio of pre hatch Cyprinus carpio. A comparative outlook made from this experimental trial that sex induction of Cyprinus carpio by eggs immersion using synthetic male steroid hormone is an alternative safe technique of fish sex reversal in contrast to oral administration of hormone in fish feed.

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Andrógenos sintéticos (hormônios masculinos) administrados ao viveiro de peixes estão sendo usados ​​na aquicultura para evitar a diferenciação sexual e a desova indesejada nos ovos ou no primeiro estágio de alimentação dos peixes. O presente estudo foi conduzido com o objetivo de produzir carpa comum masculina (Cyprinuscarpio) pela técnica de imersão em ovos. Com essa pequena percepção, o efeito de diferentes concentrações hormonais (17α-metiltestosterona @ HC: 150, 300, 450 e 600 µgl-1) com tempos de imersão (IT: 24, 48 e 72 horas) e seu efeito de interação (HC x IT) na porcentagem de eclosão dos ovos de Cyprinuscarpio, a porcentagem de sobrevivência e a porcentagem da produção masculina foram avaliadas especificamente. Os resultados mostraram que a porcentagem de incubação de ovos diminuiu com o aumento da TI da mesma forma, a sobrevivência dos alevinos tratados foi afetada pelo aumento da TI (P <0,001). O principal efeito de interação do HC x IT mostrou que o maior percentual de indivíduos do sexo masculino (95%) foi obtido com 450-600 µgl-1 HC por 72 horas de TI, seguido por 88-92,50% com 150-300 µgl-1 HC para 72 horas de TI, 87,50% às 48 horas de TI para o restante dos tratamentos hormonais, e 47,50% mais baixos foram registrados no controle (P <0,05). A porcentagem aumentada de macho de Cyprinuscarpio foi obtida com o aumento do HC em todas as TIs. Observou-se que o tratamento de imersão a 600µgl-1 por 72 horas foi mais efetivo na alteração da razão sexual do Cyprinuscarpio antes da eclosão. Uma perspectiva comparativa feita a partir deste ensaio experimental de que a indução sexual de Cyprinuscarpio por imersão de ovos usando hormônio esteróide masculino sintético é uma técnica alternativa segura de reversão do sexo em peixes, em contraste com a administração oral de hormônio na alimentação de peixes.

Asunto(s)

Animales , Masculino , Carpas/fisiología , Andrógenos/farmacología , Metiltestosterona/administración & dosificación , Razón de Masculinidad , Acuicultura , Inmersión