Aromatase Enzyme Research Articles

Identification of chalcone derivatives as putative non-steroidal aromatase inhibitors potentially useful against breast cancer by molecular docking and ADME prediction

Aromatase is an influential target to overcome estrogen receptor positive breast cancer, as the enzyme is responsible for conversion of androstenedione to estrone, a promising drug target for therapeutic management of breast cancer. Chalcones are prominent biosynthetic compounds and parent candidate for the synthesis of heterocycles with diversified biological activities. The prime objective of the present study is to evaluate the binding interaction of 2-hydroxyphenyl- prop-2-en-1-one (1A-1X), 2-hydroxy-4-methoxyphenyl- prop-2-en-1-one (3A-3X), 2,4-dihydroxyphenyl- prop-2-en-1-one (9A-9X) and 1-hydroxynaphthalen-2-yl-prop-2-en-1-one (5A-5X) derivatives with aromatase enzyme by molecular docking study and also check their ADME properties by maestro suit. The designed chalcones derivatives have been docked against our target protein with PDB id 3S7S retrieved from the protein data bank, whereas exemestane has been taken as the positive control. As docking data revealed that docking score of 1K, 1U, 1B 3K 3N, 5K, 5U, 9S, 9K, 9N and 9F compounds found less than exemestane and all of these compounds with appropriate ADME properties have proven their excellent absorption as well as solubility characteristics. The present findings provided valuable information about binding interactions of chalcones derivatives to the active site of aromatase. These compounds may serve as potential lead compound for developing new aromatase inhibitors in breast cancer treatment.

Target prediction and validation of microRNAs expressed from FSHR and aromatase genes in human ovarian granulosa cells

MicroRNAs (miRNAs) are known post-transcriptional regulators of various biological processes including ovarian follicle development. We have previously identified miRNAs from human pre-ovulatory ovarian granulosa cells that are expressed from the intronic regions of two key genes in normal follicular development: FSH receptor (FSHR) and CYP19A1, the latter encoding the aromatase enzyme. The present study aims to identify the target genes regulated by these miRNAs: hsa-miR-548ba and hsa-miR-7973, respectively. The miRNAs of interest were transfected into KGN cell line and the gene expression changes were analyzed by Affymetrix microarray. Potential miRNA-regulated genes were further filtered by bioinformatic target prediction algorithms and validated for direct miRNA:mRNA binding by luciferase reporter assay. LIFR, PTEN, NEO1 and SP110 were confirmed as targets for hsa-miR-548ba. Hsa-miR-7973 target genes ADAM19, PXDN and FMNL3 also passed all verification steps. Additionally, the expression pattern of the miRNAs was studied in human primary cumulus granulosa cell culture in relation to the expression of their host genes and FSH stimulation. Based on our findings we propose the involvement of hsa-miR-548ba in the regulation of follicle growth and activation via LIFR and PTEN. Hsa-miR-7973 may be implicated in the modulation of extracellular matrix and cell-cell interactions by regulating the expression of its identified targets.

Towards an Understanding of the Mode of Action of Human Aromatase Activity for Azoles through Quantum Chemical Descriptors-Based Regression and Structure Activity Relationship Modeling Analysis

Aromatase is an enzyme member of the cytochrome P450 superfamily coded by the CYP19A1 gene. Its main action is the conversion of androgens into estrogens, transforming androstenedione into estrone and testosterone into estradiol. This enzyme is present in several tissues and it has a key role in the maintenance of the balance of androgens and estrogens, and therefore in the regulation of the endocrine system. With regard to chemical safety and human health, azoles, which are used as agrochemicals and pharmaceuticals, are potential endocrine disruptors due to their agonist or antagonist interactions with the human aromatase enzyme. This theoretical study investigated the active agonist and antagonist properties of “chemical classes of azoles” to determine the relationships of azole interaction with CYP19A1, using stereochemical and electronic properties of the molecules through classification and multilinear regression (MLR) modeling. The antagonist activities for the same substituent on diazoles and triazoles vary with its chemical composition and its position and both heterocyclic systems require aromatic substituents. The triazoles require the spherical shape and diazoles have to be in proper proportion of the branching index and the number of ring systems for the inhibition. Considering the electronic aspects, triazole antagonist activity depends on the electrophilicity index that originates from interelectronic exchange interaction (ωHF) and the LUMO energy (), and the diazole antagonist activity originates from the penultimate orbital () of diazoles. The regression models for agonist activity show that it is opposed by the static charges but favored by the delocalized charges on the diazoles and thiazoles. This study proposes that the electron penetration of azoles toward heme group decides the binding behavior and stereochemistry requirement for antagonist activity against CYP19A1 enzyme.

In silico molecular docking and in vitro antioxidant activity studies of novel α-aminophosphonates bearing 6-amino-1,3-dimethyl uracil

In the present study, a new series of α-Aminophosphonates bearing 6-amino-1,3-dimethyluracil was synthesized in good to excellent yields (78–95%) by one-pot, three-component reaction of 6-amino-1,3-dimethyluracil, aromatic aldehydes and diethylphosphite via Kabachnik–Fields reaction by using an eco-friendly Eaton’s reagent. All the compounds were screened for in vitro antioxidant studies by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) methods. Among the synthesized bioactive molecules, 4a, 4d, 4g, and 4h exhibited promising antioxidant activity compared with the standard drug Ascorbic acid. Furthermore, in order to support the biological results of the compounds, molecular docking studies were performed against Aromatase enzyme for four compounds which revealed that the compounds 4a, 4d, 4g, and 4h have significant binding modes, with docking scores of −8.6, −8.4, −8.1 and −8.1 respectively and the compound 4b specifically has equal dock score of −8.0 when compared with the standard drug Exemestane.

Sexually dimorphic gene expression and neurite sensitivity to estradiol in fetal arcuate Kiss1 cells.

Kiss1 neurons of the arcuate (ARC) nucleus form an interconnected network of cells that communicate via neurokinin B (encoded by Tac2) and its receptor (encoded by Tacr3) and play key roles in the control of the reproductive axis through sex hormone-regulated synthesis and release of kisspeptin peptides (Kp, encoded by Kiss1). The aim of this study was to determine whether the Kiss1 cell population of the ARC already displays sexually dimorphic features at embryonic age E16.5 in mice. At this time of development, Kiss1-GFP- and Kp-immunoreactive cell bodies were restricted to the ARC and not found in the pre-optic area (POA). The Kiss1-GFP cell population was identical in size between sexes but had significantly lower Kiss1, Tac2, and Tacr3 mRNA levels and lower Kp-ir fiber density in the POA in male compared to female fetuses. Receptors for androgen (Ar) and estrogen (Esr1, Esr2, Gpr30) and the Cyp19a1 gene (encoding the estradiol-producing enzyme aromatase) transcripts were also detected in fetal ARC Kiss1-GFP cells with significant sex differences for Ar (higher in males) and Esr1 (higher in females). Functional studies on primary cultures of sorted fetal Kiss1-GFP cells revealed a significant negative effect of estradiol treatment on neurite outgrowth on the fourth day of culture in the female group specifically. We conclude that the ARC Kiss1 cell population is already sexually differentiated at E16.5 and that its morphogenetic development may be particularly vulnerable to estradiol exposure at this early developmental time.

All-Atom Simulations Disclose How Cytochrome Reductase Reshapes the Substrate Access/Egress Routes of Its Partner CYP450s.

Cytochromes P450 enzymes (CYP450s) promote the oxidative metabolism of a variety of substrates via the electrons supplied by the cytochrome P450 reductase (CPR) and upon formation of a CPR/CYP450 adduct. In spite of the pivotal regulatory importance of this process, the impact of CPR binding on the functional properties of its partner CYP450 remains elusive. By performing multiple microsecond-long all-atom molecular dynamics simulations of a 520 000-atom model of a CPR/CYP450 adduct embedded in a membrane mimic, we disclose the molecular terms for their interactions, considering the aromatase (HA) enzyme as a proxy of the CYP450 family. Our study strikingly unveils that CPR binding alters HA's functional motions, bolstering a change in the shape and type of the channels traveled by substrates/products during their access/egress to/from the enzyme's active site. Our outcomes unprecedentedly contribute to extricate the many entangled facets of the CYP450 metabolon, redrafting its intricate panorama from an atomic-level perspective.

Benzoxazole derivatives as new generation of anti-breast cancer agents.

New 2-substituted benzoxazole derivatives were synthesized and screened for their in vitro anti-proliferative activities against MCF-7 and MDA-MB-231 cell lines. Compounds 4b, 4d and 11c eliciting the highest activity against MCF-7 cells were further assayed for their cytotoxic activities against A431 and HCC827 cancer cells in addition to their in vitro inhibition of wild and mutated epidermal growth factor receptor (EGFR) enzymes. Compound 11c was the most active against A431 cells and it displayed a potent inhibition of EGFRWT while compounds 4b and 4d elicited higher potencies than erlotinib against mutated EGFRL858R. Compounds 4a, 6c and 8a showed the most potent cytotoxic activity against MDA-MB-231 cancer cells where compounds 4a and 6c were slightly less potent aromatase (ARO) inhibitors than letrozole. MCF-7 cells treated with compounds 4b, 4d, 11c and MDA-MB-231 cells treated with compounds 4a, 6c and 8a showed remarkable over-expression of caspase-9 protein level and elicited pre G1 apoptosis and cell cycle arrest at G2/M phase in addition to high annexin V binding affinity indicating significant apoptosis. Chemo-informatic and docking properties were also predicted. Docking results revealed that docked compounds displayed binding modes with EGFR and ARO enzymes comparable to that of the reference ligands. The benzoxazole derivatives 11c and 6c possessing amide and dithiocarbamate moieties respectively were found to be potent apoptosis-inducing anti-breast cancer agents with acceptable physicochemical properties. They exert their activity via inhibition of EGFR and ARO enzymes respectively.

Anastrozole-Induced Dermatitis: Report of a Woman with an Anastrozole-Associated Dermatosis and a Review of Aromatase Inhibitor-Related Cutaneous Adverse Events.

Anastrozole is an aromatase inhibitor. Anastrozole competitively inhibits the aromatase enzyme, which synthesizes estrogen. It is used for estrogen receptor-positive breast cancers. A woman with breast cancer and anastrozole-induced dermatitis is described; the cutaneous side effects associated with aromatase inhibitors are also reviewed. Skin-related adverse events associated with aromatase inhibitor use are uncommon and may be delayed in appearance; the time of onset ranges from less than 5 days to 6 months (median 2 months). They present as either vasculitis, erythema nodosum, subacute cutaneous lupus erythematosus, or other dermatoses. Some patients demonstrate cutaneous lesions at either the original site of the breast malignancy or in areas that were previously treated with surgery or radiotherapy. The skin reactions are usually treated with discontinuation of the aromatase inhibitor; topical corticosteroids or oral corticosteroids or both are also used for some patients. Our patient’s drug reaction occurred 2 months after starting the anastrozole and improved after a course of oral and topical corticosteroids. She was able to be switched to an alternate aromatase inhibitor without a recurrence of her adverse skin reaction.

Synthesis and biological assessment of a ruthenium(II) cyclopentadienyl complex in breast cancer cells and on the development of zebrafish embryos

Ruthenium-based complexes currently attract great attention as they hold promise to replace platinum-based drugs as a first line cancer treatment. Whereas ruthenium arene complexes are some of the most studied species for their potential anticancer properties, other types of ruthenium complexes have been overlooked for this purpose. Here, we report the synthesis and characterization of Ru(II) cyclopentadienyl (Cp), Ru(II) cyclooctadienyl (COD) and Ru(III) complexes bearing anastrozole or letrozole ligands, third-generation aromatase inhibitors currently used for the treatment of estrogen receptor positive (ER +) breast cancer. Among these complexes, Ru(II)Cp 2 was the only one that displayed a high stability in DMSO and in cell culture media and consequently, the only complex for which the in vitro and in vivo biological activities were investigated. Unlike anastrozole alone, complex 2 was considerably cytotoxic in vitro (IC50 values < 1 μM) in human ER + breast cancer (T47D and MCF7), triple negative breast cancer (TNBC) (MBA-MB-231), and in adrenocortical carcinoma (H295R) cells. Theoretical (docking simulation) and experimental (aromatase catalytic activity) studies suggested that an interaction between 2 and the aromatase enzyme was not likely to occur and that the bulkiness of the PPh3 ligands could be an important factor preventing the complex to reach the active site of the enzyme. Exposure of zebrafish embryos to complex 2 at concentrations around its in vitro cytotoxicity IC50 value (0.1–1 μM) did not lead to noticeable signs of toxicity over 96 h, making it a suitable candidate for further in vivo investigations. This study confirms the potential of Ru(II)Cp complexes for breast cancer therapy, more specifically against TNBCs that are usually not responsive to currently used chemotherapeutic agents.

Potential Natural Aromatase Blockers on Enhance the Frequency and Sound Quality of Male Canaries

The quality sound of singing birds strongly depends on testosterone. Unfortunately, most of the testosterone will be converted to estradiol by the aromatase enzyme. The study aimed to examine the potential of natural aromatase blockers for increasing the frequency and quality of canary chirps. Five adult male canaries, with bodyweight 25-30 g were used in the study. After being adapted for a week, birds were fed a mixture of aromatase blockers and canary seed for 20 days at a dose of 0.3 mg /30 g body weight. Quantities of a song using Hagemon touch methods were calculated by frequency of chirping for 10 minutes, whereas the quality of the song was counted by the periods of once chirping for 10 minutes. Recording begins when the bird is given standard feeding and repeated after treatment for 20 days. The results showed that the frequency of chirping before given a mixture of ingredients was 15.3 /10 min, after being treated with aromatase blockers the frequency increased up to 78.9 /10 min. The length of the tweet before treatment was &lt;1s while after treatment up to 17s. It can be concluded that aromatase blockers can increase the frequency and quality of male Canary's song.

Acidic Exopolysaccharide Produced from Marine Bacillus amyloliquefaciens 3MS 2017 for the Protection and Treatment of Breast Cancer.

Purpose:This study was planned to investigate the anti-breast-cancer property of acidic exopolysaccharide produced from marine Bacillus amyloliquefaciens 3MS 2017 (BAEPS) in an animal model, which previously showed in-vitro anti-breast-cancer activity, by studying its potential participation in various targeted mechanisms.Methods:Mammary carcinoma in female Sprague-Dawley rats, both in prophylactic and in curative designs, was chemically induced using 7,12-dimethylebenz-(a)-anthracene (DMBA). B. amyloliquefaciens 3MS 2017 anti-breast-cancer property was evaluated by studying its effects on cancer-growth-rate-limiting enzymes (aromatase and Na+/K+ ATPase), sexual hormones (estrogen and progesterone), antioxidant and inflammatory biomarkers (cyclooxygenase-1; COX-1 and cyclooxygenase-2; COX-2). The incidence of breast cancer by DMBA was dependent on the level of carcinoembryonic antigen (CEA) and aromatase.Results:7,12-Dimethylebenz-(a)-anthracene female rats were characterized by a significant increase in cancer-related biomarkers with an increase of oxidative stress biomarkers, in comparison with the negative control. Potent BAEPS anticancer activity on DMBA rats was exhibited either as a prophylactic or as a curative agent, which appeared via restoring the aromatase and Na+/K+ ATPase subunits levels and CEA close to the normal level. Besides, BAEPS modulated a sexual hormone, in comparison with the cancer control group (P ⩽ .05). B. amyloliquefaciens 3MS 2017 selectively inhibited COX-2 in parallel with promising antioxidant properties. The curative characters of BAEPS were more promising than the prophylactic.Conclusion:The anti-breast-cancer characters accompanied with a good safety margin may be attributed to its inhibitory effect on cancer-growth-rate-limiting enzymes, estrogen production, COX-2 level and lipid peroxidation, concurrent with enhancing COX-1 level, progesterone production, and antioxidant status.

CYP19A1 Gene Expression in Patients with Polycystic Ovarian Syndrome.

Context:Polycystic ovarian syndrome (PCOS) is a common endocrine system disorder among the women of reproductive age, yet the etiology of PCOS remains unclear. Infertility in females with PCOS can be caused by anovulation, high luteinizing hormone levels, and hyperandrogenism.Aims:This research analyzed the role of the aromatase gene (CYP19A1) in PCOS pathogenesis.Settings and Design:This study used an observational, cross-sectional design.Subjects and Methods:A total of 110 research participants (55 PCOS patients and 55 non-PCOS patients) were included in the study.Statistical Analysis Used:A real-time quantitative polymerase chain reaction was used to analyze the mRNA expression for aromatase in granulosa cells.Results:The relative expression of aromatase mRNA is lower in women with PCOS compared to those without PCOS (P < 0.05). Relative expression of CYP19A1 (aromatase) mRNA in PCOS group was 0.38 ± 0.25, whereas in non-PCOS group was 1.00 ± 0.00. The decline in aromatase activity contributes to an increase in testosterone level. This condition has a role in hyperandrogenism which is a typical characteristic of PCOS women. Granulosa cells in polycystic ovary undergo disturbance in the development and cannot respond to follicle-stimulating hormone (FSH) stimulation. Lack of stimulation of FSH causes induction inadequacy to aromatase enzyme activity in the aromatization process. The decline in FSH activity is caused by various factors that are associated with typical characteristics of PCOS.Conclusions:There is a decrease in the relative expression rate of granulosa cells’ aromatase mRNA in women with PCOS compared to the non-PCOS.

Elevated and diagnostic androgens of polycystic ovary syndrome.

IntroductionA genetic variation at the level of aromatase enzyme and/or androgen receptors was suggested in polycystic ovary syndrome (PCOS).Aim of the studyTo determine the androgens elevated and diagnostic for PCOS.Material and methodsA total of 120 PCOS women were compared to non-PCOS controls in this study. The studied women were evaluated thoroughly, including: day 2-3 hormonal profile and any hormonal change confirmed by two laboratory results eight weeks apart. Collected data were analysed to determine the androgens elevated and diagnostic for PCOS.ResultsThe luteinising hormone (LH) and LH/follicle stimulating hormone (FSH) ratio were significantly high in the studied PCOS group compared to controls (p = 0.02 and 0.01, respectively). In addition, total and free testosterone and androstenedione were significantly high in the studied PCOS group compared to controls (p = 0.001, 0.003, and 0.02, respectively).The studied PCOS group had higher relative risk (RR) and odds ratio (OR) of elevated total testosterone (2.4 and 5.7, respectively), elevated free testosterone (2.9 and 4.9, respectively), and elevated androstenedione (3.0 and 4.8, respectively), compared to controls.ConclusionsTestosterone (both total and free testosterone) and androstenedione were the main elevated androgens and were diagnostic for excess ovarian androgens in the studied PCOS women, whereas dehydroepiandrosterone (DHEA) was not elevated and/or diagnostic for excess ovarian androgens in the studied PCOS women.

Neurochemical characterization of the hypothalamus of the early fetal and newborn alpaca Vicugna pacos.

In this study we performed a neurochemical characterization of the hypothalamus in the developing alpaca (Vicugna pacos) with the aim of revealing the distributions of immunoreactive (-ir) cells containing parvalbumin (PV), calbindin (CB), calretinin (CR), the somatostatin (SOM), the enzyme aromatase P450 (P450Arom), the estrogen receptor α (ER-α), and estrogen receptor β (ER-β) in embryonal stages, early fetal age, and in the newborn. This analysis has been carried out on embryos at 20, 30, 45 days, fetuses at 90 days, and newborn alpaca. Our immunohistochemical results revealed no cells-ir throughout the embryonic hypothalami of 20, 30, and 45 days. On the fetal stage of 90 days, SOM-ir cells were observed in the lateral hypothalamus and the ventromedial nuclei of the tuberal region. We checked for the presence of P450Arom-ir cells in the periventricular area and dorsomedial hypothalamic nucleus of the tuberal region. In these fetal stages, no PV-ir, CB-ir, CR-ir or ERs-ir cells were identified. In the newborn, the PV-ir, CB-ir, CR-ir, and SOM-ir cells were detected in both the anterior and tuberal hypothalamic area. The P450Arom-ir cells the ER-α-ir and ER-β-ir cells were found in the anterior hypothalamus. Our results offer a contribution in the future purpose to obtain a time-expression pattern of the considered markers in alpaca during gestation and represents a foundation for future investigations on the alpaca brain to define the cross talk between PV, CB, CR, P450Arom, SOM, and ERs in the hypothalamus, the strategic region for the control of the reproductive behavior.

Testicular characterization and spermatogenesis of the hematophagous bat Diphylla ecaudata.

Diphylla ecaudata is a hematophagous bat endemic of South America, with food preference for bird blood. Given the lack of information about the reproductive activity of this species, this study aimed to describe the testicular morphology and histomorphometry of D. ecaudata in order to understand its reproductive biology, specially spermatogenesis. The animals were collected in Lajes city, Rio Grande do Norte, Brazil. Following euthanasia, the testes were histologically processed for morphological, morphometric, ultrastructural and immunohistochemical analyses. Their average body weight was 24.64g, with a gonadosomatic index of 0.49%, tubulesomatic index of 0.47%, and a total of 32.20m of seminiferous tubules per gram of testis. The pre-meiotic, meiotic, and post-meiotic phases accounted for 56.20%, 9.30%, and 34.50% of the seminiferous epithelium cycle, respectively. The ultrastructure of spermiogenesis was similar to that described in other mammals and the perforatorium was not observed in the sperm. Androgen receptors were detected in Sertoli cell nuclei and Leydig cell cytoplasm, while aromatase enzyme was detected only in Sertoli cell nuclei. FGF2 and BCL-2 activities were detected in the cytoplasm of zygotene and pachytene primary spermatocytes, as well as round and elongated spermatids. D. ecaudata showed testicular pattern similar to other mammals and characteristics common to other bat species. This species stood out for its high efficiency of Sertoli cells, which presented high capacity to support germ cells, besides the highest sperm production rates among those already recorded. This study is the first step towards the knowledge of D. ecaudata reproduction and the first description of its spermatogenesis.

Facile synthesis of two azete-steroid derivatives and theoretical evaluation of its interaction with the aromatase enzyme

Several aromatase inhibitors have used for the treatment of breast cancer; however, some of these drugs may produce some side effects such as endometrial cancer and bone loss. The aim of this study was to synthesize two new azete-steroid derivatives (compounds 9 or 10) to evaluate its theoretical interaction with an aromatase enzyme (2wd3) using anastrozole and exemestane as controls in a docking model. The preparation of 9 and 10 was carried out using a series of reactions which involves amination, etherification, nitration, and addition. Chemical structure of the compounds was confirmed using elemental analysis and NMR spectrum. The results showed that compounds 9 or 10 could bind to a different type of aminoacid residues involved in of 2wd3 protein surface compared anastrozole and exemestane; this phenomenon may exert changes in the biological activity of aromatase enzyme. All data suggest that compounds 9 or 10 could be an alternative for the treatment of breast cancer.

Steroidal alkaloids efficient aromatase inhibitors with potential for the treatment of postmenopausal breast cancer.

Plant-derived natural products are of great interest due to their diversity in modern drug discovery. Sarcococca saligna has been used for the treatment of different diseases. The present study was aimed at isolating phytochemical constituents including Alkaloid-C (a), Dictyophlebine (b), Sarcovagine-D (c) and Saracodine (d) Holaphylline (e) from Sarcococca saligna to investigate the anticancer effect of these compounds. These compounds were evaluated for inhibition of aromatase enzyme of breast cancer in assistance by molecular docking simulations to understand molecular interaction between the enzyme and ligands. The IC50 values of compound 1 and 5 were found 138.27±0.01µl and 12.91±0.01µl, respectively, and both were found active due to their bulky structures in comparison to the active site of aromatase enzyme. The standard drug exemestane showed potent activity in comparison with the test compounds, having IC50 values of 0.052±0.01µl. Both compounds showed favorable electrostatic interactions with the active site of aromatase enzyme but the shape and steric bulk of the compounds was the limiting factor in their inhibitory effects. New lead compounds could be generated after extensive modifications guided by computational and experimental tools as a possible anticancer agents by targeting aromatase enzyme.

Changes in seminal parameters and hormonal profile with use of aromatase inhibitor in management of aging broiler breeder roosters

An excessive amount of aromatase enzyme reduces reproductive performance in aging roosters. Testosterone metabolism by aromatase enzyme is one of the reasons for reduced testosterone and lower fertility of aging roosters. The purpose of this study was to determine the effects of Exemestane (EX), as a steroidal aromatase inhibitor, on the seminal parameters and reproductive hormones of aging roosters. A total of 20 roosters (45 wk of age) were housed in individual cages and received a standard basal diet and oral EX capsules for 60 D at the daily doses per rooster (mg/rooster) in the following experimental groups: 0mg (CTRL), 0.25mg (Ex-0.25), 0.5mg (Ex-0.5), and 1.5mg (Ex-1.5). Sperm samples were obtained on days 1, 20, 40, and 60 of experiment. Blood samples were taken on days 1 and 60. The results indicated that different EX dosages affected semen parameters (P < 0.05) other than semen volume, morphology, apoptosis, and acrosome integrity. Various semen characteristics were significant (P < 0.05) during different times of the experiment, with the exception of semen volume, total motility, membrane integrity, morphology, apoptosis, and acrosome integrity. Roosters that received 0.5mg of EX had higher percentages of sperm concentration, total motility, progressive motility, membrane integrity, viability, and mitochondrial activity (P < 0.05). There were lower concentrations of malondialdehyde in the CTRL (0mg) and Ex-0.25 groups (P < 0.05). Although there was no significant difference in hormones at day 0 of the experiment (P > 0.05), roosters in the Ex-0.5 had higher concentration of testosterone as well as lower of aromatase activity at day 60 (P < 0.05). It can be concluded that EX improved semen parameters and testosterone, which ultimately can increase fertility in the aging broiler breeder roosters.

Synthesis, biological evaluation, and docking study of indole aryl sulfonamides as aromatase inhibitors

In order to identify new aromatase enzyme inhibitors, thirty aryl sulfonamide derivatives containing an indole nucleus have been synthesized. The enzyme inhibition assay showed that four compounds inhibit aromatase in the sub-micromolar range. Loading concentrations of these four compounds were afterwards tested for cell viability and cytotoxicity on MCF7 human breast cancer cells, revealing a time- and dose-dependent decrease of active metabolizing cells over the time of the culture (0–72 h), starting from a concentration of 100 μM. Likewise LDH released raised up to 40% at early time of exposures (24 h). Finally, the docking study showed that the best active compounds efficiently bound in the active site of the aromatase; high values of HBD and low levels of HBA are the principal requirement evidenced by the QSAR model.

Intermittent Exercise Triggers Synthesis of CYP19 Aromatase as a Key Enzym for Estrogen Formation In Sprague Dawley Rat Bone Innovarectomy

Menopause is a permanent cessation of menstrual cycle due to reduced secretion of the hormone estrogen which can result in osteoporosis. Osteoporosis is characterized by the process of bone resorption faster than the process of bone formation, resulting in a decrease in bone mineral density and bone microarchitecture damage resulting in bones becoming brittle and easily fracturing. Physical exercise is a holistic intervention to prevent osteoporosis due to menopause. This study is a pure experimental study using a post-test only control group design research design. The subjects of the study were the 12-week-old Sprague Dawley rat. The number of groups is 5 with the number of rats per 6 animals. There was a significant difference between the ovarectomy group of rats and the ovarectomy group of mice and were given intermittent exercise treatment of CYP19 aromatase expression. Discussion: Muscle contractions that occur due to intermittent exercise treatment can produce large amounts of IL-6 and IL-6 mRNA which can stimulate estrogen production. Local estrogen production can reduce bone resorption and increase bone formation and bone density Intermittent exercise can trigger the process of the synthesis of the CYP19 aromatase enzyme in ovarectomy rat femur bones