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Sawa Horie, Akiko Yamaki, Shigeru Takami
Although several lines of evidence have suggested that sex steroids influence olfaction, little is known about the cellular basis of steroid-metabolizing enzymes in the olfactory system. Thus, we aimed to examine gene expression and immunolocalization of four sex steroid-metabolizing enzymes in the olfactory mucosa (OM) of albino rats; steroid side chain-cleaving enzyme (P450scc), 17β -hydroxysteroid dehydrogenase type 1 (17β -HSD-1), 17β -HSD type 2 (17β -HSD-2), and aromatase. P450scc is known to catalyze conversion from cholesterol to pregnenolone...
October 13, 2016: Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology
Marjaana Viljanto, James Scarth, Pamela Hincks, Lynn Hillyer, Adam Cawley, Craig Suann, Glenys Noble, Christopher J Walker, Andrew T Kicman, Mark C Parkin
Detection of testosterone and/or its pro-drugs in the gelding is currently regulated by the application of an international threshold for urinary testosterone of 20 ng/mL. The use of steroid ratios may provide a useful supplementary approach to aid in differentiating between the administration of these steroids and unusual physiological conditions that may result in atypically high testosterone concentrations. In the current study, an ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed to quantify testosterone (T) and epitestosterone (E)...
October 7, 2016: Drug Testing and Analysis
Lisandra L Martin, Clemens Kubeil, Alexandr N Simonov, Vladimir L Kuznetsov, C Jo Corbin, Richard J Auchus, Alan J Conley, Alan M Bond, Raymond J Rodgers
Within the superfamily of cytochrome P450 enzymes (P450s), there is a small class which is functionally employed for steroid biosynthesis. The enzymes in this class appear to have a small active site to accommodate the steroid substrates specifically and snuggly, prior to the redox transformation or hydroxylation to form a product. Cytochrome P450c17 is one of these and is also a multi-functional P450, with two activities, the first 17α-hydroxylation of pregnenolone is followed by a subsequent 17,20-lyase transformation to dehydroepiandrosterone (DHEA) as the dominant pathways to cortisol precursors or androgens in humans, respectively...
October 3, 2016: Molecular and Cellular Endocrinology
Jeremy J Allen, Susan L Herrick, Joanne E Fortune
In cattle, primordial follicles form before birth. Fetal ovarian capacity to produce progesterone and estradiol is high before follicle formation begins and decreases around the time follicles first appear (around 90 days of gestation). However, mechanisms that regulate steroid production during this time remain unclear. We hypothesized that LH stimulates progesterone and androgen production and that FSH stimulates aromatization of androgens to estradiol. To test this, we cultured pieces from fetal bovine ovaries for 10 days without or with exogenous hormones and then measured the accumulation of steroids in the culture medium by RIA...
October 3, 2016: Journal of Molecular Endocrinology
Manoj Prasad, Anna N Walker, Jasmeet Kaur, James L Thomas, Shirley A Powell, Amit V Pandey, Randy M Whittal, William E Burak, Guy Petruzzelli, Himangshu S Bose
The acute response to stress consists of a series of physiological programs to promote survival by generating glucocorticoids and activating stress-response genes that increase the synthesis of many chaperone proteins specific to individual organelles. In the endoplasmic reticulum (ER), short-term stress triggers activation of the unfolded protein response (UPR) module that either leads to neutralization of the initial stress or adaption to it; chronic stress favors cell death. UPR induces expression of the transcription factor, C/EBP homology protein (CHOP), and its deletion protects against the lethal consequences of prolonged UPR...
October 3, 2016: Molecular and Cellular Biology
Kathrine Eggers Pedersen, Robert J Letcher, Christian Sonne, Rune Dietz, Bjarne Styrishave
Per- and polyfluoroalkyl substances (PFASs) are emerging in the Arctic and accumulate in brain tissues of East Greenland (EG) polar bears. In vitro studies have shown that PFASs might possess endocrine disrupting abilities and therefore the present study was conducted to investigate potential PFAS induced alterations in brain steroid concentrations. The concentrations of eleven steroid hormones were determined in eight brain regions from ten EG polar bears. Pregnenolone (PRE), the dominant progestagen, was found in mean concentrations of 5-47ng/g (ww) depending on brain region...
September 27, 2016: Environment International
Cuiping Pang, Yuting Cao, Xiangdong Zhu
Nowadays, there are a few steroid drugs or intermediates that have been obtained via the transformation of microorganisms, and many strains of transformed steroids have not been found yet. Therefore, it is very significant to screen for the strains that have the abilities to transform steroids to produce valuable products. This study has focused on the screen and identification of strains, the structural identification of converted products, and the optimization of transformation conditions, as well as the establishment of transformation systems...
September 30, 2016: Journal of Basic Microbiology
Youqiong Wang, Lipeng Tang, Wei Yin, Jiesi Chen, Tiandong Leng, Xiaoke Zheng, Wenbo Zhu, Haipeng Zhang, Pengxin Qiu, Xiaoxiao Yang, Guangmei Yan, Haiyan Hu
Sensitive and specific biomarkers are required for the diagnosis and treatment of depression because the existing diagnostic criteria are subjective and could produce false positives or negatives. Some endogenous neuroactive steroids that have shown either antidepressant effects or concentration changes in individuals with depression could provide potential biomarkers. In this study, a simple and specific method was developed to simultaneously determine seven endogenous neuroactive steroids in biological samples: cortisone, cortisol, dehydroepiandrosterone, estradiol, progesterone, pregnenolone, and testosterone...
2016: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
Shin-Hye Kim, Ju-Yeon Moon, Hironobu Sasano, Man Ho Choi, Mi-Jung Park
CONTEXT: Pediatric obesity has been related to hyperandrogenism and premature adrenarche in previous studies. However, little is known regarding the association between body fat mass and steroidogenic enzyme activities in children. OBJECTIVE: To examine whether body fat mass is associated with serum steroid profiles in girls. DESIGN, PARTICIPANTS, AND SETTING: We enrolled 242 girls (125 prepubertal, 117 pubertal; aged 7-13 years). Early morning blood samples were drawn at a university hospital to measure serum steroid profiles using gas chromatography-mass spectrometry, and steroidogenic enzyme activities were assessed from the ratios of steroid metabolites...
September 20, 2016: Journal of Clinical Endocrinology and Metabolism
Juilee Rege, Shigehiro Karashima, Antonio M Lerario, Joshua M Smith, Richard J Auchus, Josephine Z Kasa-Vubu, Hironobu Sasano, Yasuhiro Nakamura, Perrin C White, William E Rainey
CONTEXT: Adrenal production of dehydroepiandrosterone sulfate (DHEA-S) increases throughout childhood owing to expansion of the zona reticularis (ZR). ZR features cells with a steroidogenic phenotype distinct from that of the adjacent zona fasciculata (ZF), with higher expression of cytochrome b5 type A (CYB5A) and steroid sulfotransferase type 2A1 (SULT2A1) but decreased 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2). In addition to DHEA-S, three adrenal Δ5-steroid sulfates could provide additional tools to define adrenal maturation...
September 13, 2016: Journal of Clinical Endocrinology and Metabolism
Richard J Servatius, Christine E Marx, Swamini Sinha, Pelin Avcu, Jason D Kilts, Jennifer C Naylor, Kevin C H Pang
Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON)...
2016: Frontiers in Neuroscience
Shaheena Parween, Florence Roucher Boulez, Christa E Flück, Anne Lienhardt-Roussie, Delphine Mallet, Yves Morel, Amit V Pandey
CONTEXT: P450 oxidoreductase (POR) is required for the activities of steroid metabolizing cytochrome P450 enzymes in the endoplasmic reticulum. P450 oxidoreductase deficiency (PORD) is a form of congenital adrenal hyperplasia. Objective and Aim: Enzymatic and structural analysis of a novel L374H POR mutation from a patient with 46, XX disorder of sexual development. Design, setting, patient and intervention: 46,XX girl with non-consanguineous Turkish parents. Virilized external genitalia at birth; uterus and ovaries present, no sign of Antley-Bixler syndrome...
September 7, 2016: Journal of Clinical Endocrinology and Metabolism
Abdelmoneim Khashana, Timo Saarela, Mika Ramet, Mikko Hallman
OBJECTIVE: Therapy-resistant hypotension complicates diseases in neonates. Our objective was to investigate whether lack of therapeutic response to plasma expanders and inotropes associates with serum levels of cortisol and its precursors. METHODS: We investigated 96 infants with hypotension and critical neonatal disease for cortisol metabolism and are divided into responders and non-responders to plasma expanders and inotropes. Serum concentrations of steroids were analysed soon after the onset of volume expansion and inotrope treatment for shock...
August 31, 2016: Journal of Maternal-fetal & Neonatal Medicine
Hisashi Masuyama, Keiichiro Nakamura, Etsuko Nobumoto, Yuji Hiramatsu
Epithelial ovarian cancer remains the most devastating gynecologic cancer with drug resistance and rapid recurrence. Pregnane X receptor (PXR) is a nuclear receptor that affects drug metabolism/efflux and drug-drug interaction through control of multiple drug resistance 1 (MDR1), which implies a major role in multidrug resistance, and other genes. We examined whether the inhibition of PXR-mediated pathway using siRNA interference and an antagonist for PXR could influence the paclitaxel and cisplatin cytotoxicity in ovarian cancer cells...
September 2016: International Journal of Oncology
Francis K Yoshimoto, I-Ji Jung, Sandeep Goyal, Eric Gonzalez, F Peter Guengerich
The enzyme cytochrome P450 11A1 cleaves the C20-C22 carbon-carbon bond of cholesterol to form pregnenolone, the first 21-carbon precursor of all steroid hormones. Various reaction mechanisms are possible for the carbon-carbon bond cleavage step of P450 11A1, and most current proposals involve the oxoferryl active species, Compound I (FeO(3+)). Compound I can either (i) abstract an O-H hydrogen atom or (ii) be attacked by a nucleophilic hydroxy group of its substrate, 20R,22R-dihydroxycholesterol. The mechanism of this carbon-carbon bond cleavage step was tested using (18)O-labeled molecular oxygen and purified P450 11A1...
September 21, 2016: Journal of the American Chemical Society
Erin L Legacki, C J Corbin, B A Ball, M Wynn, S Loux, S D Stanley, A J Conley
Mammalian pregnancies need progestogenic support and birth requires progestin withdrawal. The absence of progesterone in pregnant mares, and the progestogenic bioactivity of 5α-dihydroprogesterone (DHP), led us to reexamine progestin withdrawal at foaling. Systemic pregnane concentrations (DHP, allopregnanolone, pregnenolone, 5α-pregnane-3β, 20α-diol (3β,20αDHP), 20α-hydroxy-5α-dihydroprogesterone (20αDHP)) and progesterone) were monitored in mares for 10days before foaling (n=7) by liquid chromatography-mass spectrometry...
October 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Pia Elustondo, Laura A Martin, Barbara Karten
All animal subcellular membranes require cholesterol, which influences membrane fluidity and permeability, fission and fusion processes, and membrane protein function. The distribution of cholesterol among subcellular membranes is highly heterogeneous and the cholesterol content of each membrane must be carefully regulated. Compared to other subcellular membranes, mitochondrial membranes are cholesterol-poor, particularly the inner mitochondrial membrane (IMM). As a result, steroidogenesis can be controlled through the delivery of cholesterol to the IMM, where it is converted to pregnenolone...
August 23, 2016: Biochimica et Biophysica Acta
Timothy J Wilding, Melany N Lopez, James E Huettner
UNLABELLED: NMDA receptors are ligand-gated ion channels that underlie transmission at excitatory synapses and play an important role in regulating synaptic strength and stability. Functional NMDA receptors require two copies of the GluN1 subunit coassembled with GluN2 (and/or GluN3) subunits into a heteromeric tetramer. A diverse array of allosteric modulators can upregulate or downregulate NMDA receptor activity. These modulators include both synthetic compounds and endogenous modulators, such as cis-unsaturated fatty acids, 24(S)-hydroxycholesterol, and various neurosteroids...
August 24, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Ana Belen Lopez-Rodriguez, Estefania Acaz-Fonseca, Roberto Spezzano, Silvia Giatti, Donatella Caruso, Maria-Paz Viveros, Roberto C Melcangi, Luis M Garcia-Segura
The incidence of traumatic brain injuries (TBIs) in humans has rapidly increased in the last ten years. The most common causes are falls and car accidents. Approximately 80 000-90 000 persons per year will suffer some permanent disability as a result of the lesion, and one of the most common symptoms is the decline of hormone levels, also known as post-TBI hormonal deficiency syndrome. This issue has become more and more important, and many studies have focused on shedding some light on it. The hormonal decline affects not only gonadal steroid hormones but also neuroactive steroids, which play an important role in TBI recovery by neuroprotective and neurotrophic actions...
October 2016: Endocrinology
Alberto Sánchez-Guijo, Jens Neunzig, Adrian Gerber, Vinzenz Oji, Michaela F Hartmann, Hans-Christian Schuppe, Heiko Traupe, Rita Bernhardt, Stefan A Wudy
The impact of steroid sulfatase (STS) activity in the circulating levels of both sulfated and unconjugated steroids is only partially known. In addition, the sulfated steroid pathway, a parallel pathway to the one for unconjugated steroids, which uses the same enzymes, has never been characterized in detail before. Patients with steroid sulfatase deficiency (STSD) are unable to enzymatically convert sulfated steroids into their unconjugated forms, and are a good model to elucidate how STS affects steroid biosynthesis and to study the metabolism of sulfated steroids...
December 5, 2016: Molecular and Cellular Endocrinology
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