scholarly journals Bisphenol A Modifies the Regulation Exerted by Testosterone on 5α-Reductase Isozymes in Ventral Prostate of Adult Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Pilar Sánchez ◽  
Beatriz Castro ◽  
Jesús M. Torres ◽  
Asunción Olmo ◽  
Raimundo G. del Moral ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Prostate Gland ◽  
Ventral Prostate ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Adult Rats ◽  
Short Term Exposure ◽  
Rat Prostate ◽  
And Function ◽  
Dose Dependent

The development, growth, and function of the prostate gland depend on androgen stimulation. The primary androgen in prostate is 5α-dihydrotestosterone (DHT) which is synthesized from circulating testosterone (T) through the action of 5α-reductase (5α-R). Although 5α-R occurs as five isozymes, only 5α-R1 and 5α-R2 are physiologically involved in steroidogenesis. The endocrine disruptor bisphenol A (BPA) alters sexual organs, including the prostate. Our previous findings indicated that BPA decreased the expression of 5α-R1 and 5α-R2 in rat prostate but also circulating T. Thus, it is unclear whether BPA exerts this effect on 5α-R isozymes by reducing circulating T or by any other mechanism. In this study, we examine the effects of short-term exposure to BPA at doses below 25 μg/Kg/d and above 300 μg/Kg/d of the TDI on mRNA levels of 5α-R1 and 5α-R2 in prostate of adult castrated rats supplemented with T to achieve constant circulating T levels. mRNA levels were measured by absolute quantitative RT-PCR, T levels by RIA, and DHT levels by ELISA. Our results indicated that in castrated rats treated with T BPA at the two doses studied significantly decreased the mRNA levels of both 5α-R isozymes in a dose-dependent manner without modifications in circulating T.

ICI 176,334: A NOVEL NON–STEROIDAL, PERIPHERALLY SELECTIVE ANTIANDROGEN

1987 ◽  
Vol 113 (3) ◽  
pp. R7-R9 ◽  
Author(s):  
B.J.A. Furr ◽  
B. Valcaccia ◽  
B. Curry ◽  
J.R. Woodburn ◽  
G. Chesterson ◽  
...  
Keyword(s):  
Testosterone Propionate ◽  
Prostate Gland ◽  
Ventral Prostate ◽  
Adult Rats ◽  
Androgen Action ◽  
Serum Lh ◽  
Accessory Sex Organs ◽  
Hypothalamic Pituitary Axis ◽  
Rat Prostate ◽  
Higher Doses

ABSTRACT Pure antiandrogens, like flutamide, antagonize androgen action both peripherally and centrally at the hypothalamic–pituitary axis, which leads to an increase in LH and testosterone secretion. A new non–steroidal antiandrogen ICI 176,334 ((2RS)4′-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3′-trifluoromethyl)propion-anilide) has now been discovered which causes regression of the accessory sex organs but does not increase serum concentrations of LH and androgens. ICI 176,334 binds to rat prostate androgen receptors with an affinity around fourfold that of hydroxyflutamide. When administered s.c. concurrently with testosterone propionate (200μg/kg) for 7 days to immature castrated rats, ICI 176,334 (10mg/kg) significantly (P<0.001) inhibited growth of the seminal vesicles and ventral prostate gland. Oral administration of ICI 176,334 at doses of 1, 5 and 25mg/kg for 14 days to adult rats caused a dose–related reduction in accessory sex organ weights but had no effect on the testes. None of these doses caused a significant increase in serum LH and testosterone. Flutamide was around fourfold less potent and significantly increased serum LH and testosterone at the higher doses. ICI 176,334 was well tolerated. ICI 176,334 should, therefore, prove useful for the treatment of androgen–responsive benign and malignant diseases.

THE BINDING OF [1,2-3H]TESTOSTERONE WITHIN NUCLEI OF THE RAT PROSTATE

1969 ◽  
Vol 44 (3) ◽  
pp. 323-333 ◽  
Author(s):  
W. I. P. MAINWARING
Keyword(s):  
Molecular Weight ◽  
Equilibrium Dialysis ◽  
Prostate Gland ◽  
Ventral Prostate ◽  
Rat Tissues ◽  
Receptor Complex ◽  
Rat Prostate ◽  
Binding Component

SUMMARY The specificity of the binding of [1,2-3H]testosterone to nuclei of various rat tissues in vivo has been studied. A significant amount of radioactivity was retained in the nuclei of androgen-dependent tissues only, particularly the ventral prostate gland. The bound radioactivity was only partially recovered as [1,2-3H]testosterone; the remainder was identified as [3H]5α-dihydrotestosterone. Efforts were made to characterize the binding component, or 'receptor', in prostatic nuclei. On digestion of nuclei labelled in vivo with [1,2-3H]testosterone, with enzymes of narrow substrate specificity, only trypsin released tritium, suggesting that the receptor is a protein. On the basis of subfractionation studies of labelled nuclei, the receptor is an acidic protein. The androgen—receptor complex could be effectively extracted from the prostatic nuclei in 1 m-NaCl and from the results of fractionations on a calibrated agarose column, the complex has a molecular weight 100,000–120,000. The specificity of the binding of steroids to such 1 m-NaCl extracts in vitro was investigated by the equilibrium dialysis procedure. Under these conditions, the specificity of the binding of [1,2-3H]testosterone demonstrated in vivo could not be simulated. The receptor is probably part of the chromatin complex but its precise intranuclear localization cannot be determined by biochemical procedures alone.

Royal Jelly Reduces Melanin Synthesis Through Down-Regulation of Tyrosinase Expression

2011 ◽  
Vol 39 (06) ◽  
pp. 1253-1260 ◽  
Author(s):  
Sang Mi Han ◽  
Joo Hong Yeo ◽  
Yoon Hee Cho ◽  
Sok Cheon Pak
Keyword(s):  
Royal Jelly ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Melanin Synthesis ◽  
Mrna Transcription ◽  
Down Regulation ◽  
Melanin Biosynthesis ◽  
Skin Whitening ◽  
Key Enzyme ◽  
Dose Dependent

For cosmetic reasons, the demand for effective and safe skin-whitening agents is high. Since the key enzyme in the melanin synthetic pathway is tyrosinase, many depigmenting agents in the treatment of hyperpigmentation act as tyrosinase inhibitors. In this study, we have investigated the hypo-pigmentary mechanism of royal jelly in a mouse melanocyte cell line, B16F1. Treatment of B16F1 cells with royal jelly markedly inhibited melanin biosynthesis in a dose-dependent manner. Decreased melanin content occurred through the decrease of tyrosinase activity. The mRNA levels of tyrosinase were also reduced by royal jelly. These results suggest that royal jelly reduces melanin synthesis by down-regulation of tyrosinase mRNA transcription and serves as a new candidate in the design of new skin-whitening or therapeutic agents.

scholarly journals Endogenous H2S is required for hypoxic sensing by carotid body glomus cells

2012 ◽  
Vol 303 (9) ◽  
pp. C916-C923 ◽  
Author(s):  
Vladislav V. Makarenko ◽  
Jayasri Nanduri ◽  
Gayatri Raghuraman ◽  
Aaron P. Fox ◽  
Moataz M. Gadalla ◽  
...  
Keyword(s):  
Carotid Body ◽  
Time Course ◽  
Channel Blocker ◽  
Primary Site ◽  
Dependent Manner ◽  
Free Medium ◽  
Adult Rats ◽  
Glomus Cells ◽  
Dose Dependent ◽  
Carotid Body Glomus Cells

H2S generated by the enzyme cystathionine-γ-lyase (CSE) has been implicated in O2 sensing by the carotid body. The objectives of the present study were to determine whether glomus cells, the primary site of hypoxic sensing in the carotid body, generate H2S in an O2-sensitive manner and whether endogenous H2S is required for O2 sensing by glomus cells. Experiments were performed on glomus cells harvested from anesthetized adult rats as well as age and sex-matched CSE+/+ and CSE−/− mice. Physiological levels of hypoxia (Po2 ∼30 mmHg) increased H2S levels in glomus cells, and dl-propargylglycine (PAG), a CSE inhibitor, prevented this response in a dose-dependent manner. Catecholamine (CA) secretion from glomus cells was monitored by carbon-fiber amperometry. Hypoxia increased CA secretion from rat and mouse glomus cells, and this response was markedly attenuated by PAG and in cells from CSE−/− mice. CA secretion evoked by 40 mM KCl, however, was unaffected by PAG or CSE deletion. Exogenous application of a H2S donor (50 μM NaHS) increased cytosolic Ca2+ concentration ([Ca2+]i) in glomus cells, with a time course and magnitude that are similar to that produced by hypoxia. [Ca2+]i responses to NaHS and hypoxia were markedly attenuated in the presence of Ca2+-free medium or cadmium chloride, a pan voltage-gated Ca2+ channel blocker, or nifedipine, an L-type Ca2+ channel inhibitor, suggesting that both hypoxia and H2S share common Ca2+-activating mechanisms. These results demonstrate that H2S generated by CSE is a physiologic mediator of the glomus cell's response to hypoxia.

Abstract 492: Arachidonic Acid Induces Activation of Platelet PF4 and Par-1 mRNA, Which Is Attenuated by Aspirin

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Liang Hu ◽  
Michael A Nardi ◽  
Michael Merolla ◽  
Yajaira Suarez ◽  
Jeffrey Berger
Keyword(s):  
Arachidonic Acid ◽  
Platelet Activation ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Thiazole Orange ◽  
Platelet Activity ◽  
Protein Levels ◽  
Reticulated Platelets ◽  
Mrna And Protein Expression ◽  
Dose Dependent

Arachidonic acid (AA) is converted to thromboxane A2 via the cyclooxygenase pathway; however its exact mechanism of platelet activation is uncertain. Inhibition of this pathway via aspirin highlights the importance of this pathway in decreasing thrombotic events. In the present study, we investigate the effect of AA on platelet activity indicators (leukocyte- and monocyte-platelet aggregation [LPA, MPA] and reticulated platelets [RP]), as well as the expression (mRNA and protein) of platelet markers PF4 and Par-1, previously well established platelet transcripts with quantitative determinations. To this end, whole blood was incubated with AA (150mM) for 30 min at room temperature in the absence or presence of aspirin (1mM) prior to addition of antibodies for platelet activity indicators, and isolating platelets for mRNA and protein expression. LPA and MPA were significantly increased after AA stimulation in a dose dependent manner, and were inhibited by aspirin treatment. AA significantly increased PF4 and Par-1 protein level as determined by flow cytometry and western blot assays. Pretreatment with aspirin also attenuated this increase in protein levels. Surprisingly, AA stimulation significantly increased thiazole orange staining (a measure of nucleic acids), another marker of increased platelet activity. Importantly, these results suggest that AA-mediated platelet activation produced an overall increase in platelet total RNA content. To confirm these findings, we analyzed the mRNA expression of PF4 and Par-1 by quantitative real time PCR from platelets treated with AA. Interestingly, AA significantly up-regulated the platelet mRNA transcripts of PF4 and Par-1 by 40% to 60%, and pretreatment with aspirin completely attenuated this effect supporting the specificity of the AA effect on platelet RNA. Altogether, these data suggest that platelet mRNA is affected by AA stimulation, which is attenuated by pretreatment with aspirin. However, the mechanisms responsible for the increased mRNA levels and expression of PF4 and Par-1 (processing of pre-RNA to mRNA) require further investigation. Importantly, our findings provide novel insight regarding platelet activation and a better understanding of mediators in the processes of thrombosis and hemostasis.

Physiological concentrations of insulin and T3 stimulate 3T3-L1 adipocyte acyl-CoA synthetase gene transcription

1996 ◽  
Vol 270 (5) ◽  
pp. E873-E881 ◽  
Author(s):  
M. S. Kansara ◽  
A. K. Mehra ◽  
J. Von Hagen ◽  
E. Kabotyansky ◽  
P. J. Smith
Keyword(s):  
Gene Transcription ◽  
Fold Increase ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Long Chain Fatty Acids ◽  
Reciprocal Regulation ◽  
Stearoyl Coa Desaturase ◽  
Dose Dependent ◽  
Long Chain ◽  
Stimulation Of

Acyl-CoAsynthetase (ACS) is a key gene for cellular utilization of long-chain fatty acids. We characterized its regulation by physiological concentrations of insulin that acutely regulate metabolism. Our results demonstrate that subnanomolar insulin rapidly and maximally stimulates ACS gene transcription in the absence of protein synthesis; 0.5 nM insulin produced a 2.3 +/- 0.1-fold increase in ACS mRNA levels and induced ACS gene transcription 2.4 +/- 0.3-fold. The insulin sensitivity of ACS was compared with lipoprotein lipase (LPL) and stearoyl-CoA desaturase-1 (SCD-1), which were both less sensitive to insulin. Physiological triiodothyronine (10 nm) also induced ACS mRNA 2.4 +/- 0.1-fold and gene transcription 2.8 +/- 0.3-fold and coordinately induced LPL and SCD-1 mRNA and gene transcription. Because insulin and adenosine 3',5'-cyclic monophosphate often regulate genes involved in lipid and carbohydrate metabolism in a reciprocal manner, we evaluated effects of 1-methyl-3-isobutylxanthine (MIX).ACS mRNA levels were strongly downregulated by MIX in a dose-dependent manner, and ACS gene transcription inhibited in a coordinate manner with LPL and SCD-1. These data demonstrate a uniquely sensitive pattern of stimulation of ACS gene transcription by insulin with reciprocal regulation by MIX, and they suggest a significant role for ACS as a tightly regulated “gatekeeper” gene participating in the control of adipocyte metabolism.

Differential modulation of innate immune response by epinephrine and estradiol

2017 ◽  
Vol 30 (3) ◽  
Author(s):  
Sona Margaryan ◽  
Armenuhi Hyusyan ◽  
Anush Martirosyan ◽  
Shushan Sargsian ◽  
Gayane Manukyan
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Inflammatory Responses ◽  
Innate Immune ◽  
Dependent Manner ◽  
Induced Expression ◽  
Short Term Exposure ◽  
Tnf Α ◽  
Vitro Effect ◽  
Dose Dependent

AbstractBackgroundAlthough it is widely accepted that catecholamines and estrogens influence immunity and have consequences for health, their effect on innate immunity (e.g. monocytes and neutrophils) is still not fully investigated.Materials and methodsOur study aimed to analyze the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, monocyte chemoattractant protein (MCP)-1 and IL-8 by whole blood cells following short-term exposure to epinephrine (Epi) and 17β-estradiol (E2) in the presence or absence of lipopolysaccharide (LPS). We also evaluated the in vitro effect of these hormones on expression of β2 integrin (CD11b/CD18) and L-selectin (CD62L) by circulating neutrophils and monocytes in the blood of healthy subjects.ResultsEpi has shown a potential to modulate the production of pro-inflammatory mediators. Its exposure resulted in significantly increased production of IL-8 in a dose-dependent manner. On the contrary, a dose-dependent suppression of LPS-induced production of IL-1β, IL-8, and MCP-1 by Epi was observed. In neutrophils, a modest rise in CD11b expression was observed after Epi exposure. Simultaneously, Epi suppressed LPS-induced expression of CD11b and CD18. In monocytes, Epi suppressed LPS-induced expression of C11b. E2 inhibited LPS-induced TNF-α production and caused a significant decrease in CD62L expression in both cell populations. No significant changes were observed after double exposure of cells with Epi and E2.ConclusionsThus, our results show that Epi and E2 differentially modulate the innate immune response and have a dual effect on cytokine modulation. The findings suggest that the observed immunoregulatory role of Epi and E2 may influence the outcome in endotoxin responses and can be critical in the regulation of inflammatory responses.

scholarly journals Suppression of the GnRH Pulse Generator by Neurokinin B Involves a κ-Opioid Receptor-Dependent Mechanism

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4894-4904 ◽  
Author(s):  
P. Grachev ◽  
X. F. Li ◽  
J. S. Kinsey-Jones ◽  
A. L. di Domenico ◽  
R. P. Millar ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Pulse Generator ◽  
Pulse Frequency ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Neurokinin B ◽  
Kndy Neurons ◽  
Lh Secretion ◽  
Dose Dependent

Abstract Neurokinin B (NKB) and its receptor (NK3R) are coexpressed with kisspeptin, Dynorphin A (Dyn), and their receptors [G-protein-coupled receptor-54 (GPR54)] and κ-opioid receptor (KOR), respectively] within kisspeptin/NKB/Dyn (KNDy) neurons in the hypothalamic arcuate nucleus (ARC), the proposed site of the GnRH pulse generator. Much previous research has employed intracerebroventricular (icv) administration of KNDy agonists and antagonists to address the functions of KNDy neurons. We performed a series of in vivo neuropharmacological experiments aiming to determine the role of NKB/NK3R signaling in modulating the GnRH pulse generator and elucidate the interaction between KNDy neuropeptide signaling systems, targeting our interventions to ARC KNDy neurons. First, we investigated the effect of intra-ARC administration of the selective NK3R agonist, senktide, on pulsatile LH secretion using a frequent automated serial sampling method to obtain blood samples from freely moving ovariectomized 17β-estradiol-replaced rats. Our results show that senktide suppresses LH pulses in a dose-dependent manner. Intra-ARC administration of U50488, a selective KOR agonist, also caused a dose-dependent, albeit more modest, decrease in LH pulse frequency. Thus we tested the hypothesis that Dyn/KOR signaling localized to the ARC mediates the senktide-induced suppression of the LH pulse by profiling pulsatile LH secretion in response to senktide in rats pretreated with nor-binaltorphimine, a selective KOR antagonist. We show that nor-binaltorphimine blocks the senktide-induced suppression of pulsatile LH secretion but does not affect LH pulse frequency per se. In order to address the effects of acute activation of ARC NK3R, we quantified (using quantitative RT-PCR) changes in mRNA levels of KNDy-associated genes in hypothalamic micropunches following intra-ARC administration of senktide. Senktide down-regulated expression of genes encoding GnRH and GPR54 (GNRH1 and Kiss1r, respectively), but did not affect the expression of Kiss1 (which encodes kisspeptin). We conclude that NKB suppresses the GnRH pulse generator in a KOR-dependent fashion and regulates gene expression in GnRH neurons.

scholarly journals Damaging Effects of Bisphenol A on the Kidney and the Protection by Melatonin: Emerging Evidences from In Vivo and In Vitro Studies

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Anongporn Kobroob ◽  
Wachirasek Peerapanyasut ◽  
Nipon Chattipakorn ◽  
Orawan Wongmekiat
Keyword(s):  
Oxidative Stress ◽  
Bisphenol A ◽  
Mitochondrial Function ◽  
Dependent Manner ◽  
Redox Equilibrium ◽  
Membrane Potential Change ◽  
Kidney Mitochondria ◽  
Dose Dependent

This study investigates the effects of bisphenol A (BPA) contamination on the kidney and the possible protection by melatonin in experimental rats and isolated mitochondrial models. Rats exposed to BPA (50, 100, and 150 mg/kg, i.p.) for 5 weeks demonstrated renal damages as evident by increased serum urea and creatinine and decreased creatinine clearance, together with the presence of proteinuria and glomerular injuries in a dose-dependent manner. These changes were associated with increased lipid peroxidation and decreased antioxidant glutathione and superoxide dismutase. Mitochondrial dysfunction was also evident as indicated by increased reactive oxygen species production, decreased membrane potential change, and mitochondrial swelling. Coadministration of melatonin resulted in the reversal of all the changes caused by BPA. Studies using isolated mitochondria showed that BPA incubation produced dose-dependent impairment in mitochondrial function. Preincubation with melatonin was able to sustain mitochondrial function and architecture and decreases oxidative stress upon exposure to BPA. The findings indicated that BPA is capable of acting directly on the kidney mitochondria, causing mitochondrial oxidative stress, dysfunction, and subsequently, leading to whole organ damage. Emerging evidence further suggests the protective benefits of melatonin against BPA nephrotoxicity, which may be mediated, in part, by its ability to diminish oxidative stress and maintain redox equilibrium within the mitochondria.

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