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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 73 records · Page 4
All sourcesNASA NTRSDOE OSTI
NASA NTRS1992

The Language Research Center's Computerized Test System for environmental enrichment and psychological assessment

In the spring of 1987, we undertook to provide environmental enrichment to nonhuman primate subjects in ways that would complement and even contribute to the bio-behaviorial science that justified the monkeys' captivity. Of course, the psychological well-being of captive primates--and indeed all research species-- has been an area of intense research activity since the 1985 amendment of the Animal Welfare Act. This mandate for researchers to ensure the psychological, as well as physical, fitness of experimental animals catalyzed the humane and scientific interests of the research community. The contemporary literature is replete with proposed means both of assaying and of providing enrichment and well-being. Notwithstanding, consensus on either assessment or intervention has yet to be reached. The paradigm we employed was modelled after successful efforts with chimpanzees. An automated test system was constructed in which subjects responded to computer tasks by manipulating a joystick. The tasks, interactive game-like versions of many of the classic testing paradigms of cognitive and comparative psychology, permitted the controlled presentation of stimuli and demands without the required presence of a human experimenter. Despite significant barriers to the success, rhesus monkeys (Macaca mulatta) and a variety of other primate species (including, of course, humans) have mastered the skills necessary for testing in this paradigm. Previous experiments have illustrated the utility of the test system for addressing questions of learning, memory, attention, perception, and motivation. Additional data have been reported to support the contention that the Language Research Center's Computerized Test System (LRC-CTS) serves its other raison d'etre--providing environmental enrichment and assessing psychological well-being. This paper is designed to augment previous descriptions of the technology and the paradigm for scientists and caretakers interested in environmental enrichment and performance assessment with primates.

Non-NASA Center↗
NASA NTRS1997

AMOS: Generic Planetary Mission Ops

The spacecraft control community is focusing increasing attention on various forms of architectures. Studies on software architectures and related technologies have been commissioned by DOD programs. The purpose of planning a series of annual workshops is to bring together participants working in the Spacecraft Ground System (SGS) domain. The overall intent of these workshops is to expedite the transition to common consensus-based open software architectures for SGSs.

workshops SGS technologies↗
NASA NTRS1995

Structural characterization and regulatory element analysis of the heart isoform of cytochrome c oxidase VIa

In order to investigate the mechanism(s) governing the striated muscle-specific expression of cytochrome c oxidase VIaH we have characterized the murine gene and analyzed its transcriptional regulatory elements in skeletal myogenic cell lines. The gene is single copy, spans 689 base pairs (bp), and is comprised of three exons. The 5'-ends of transcripts from the gene are heterogeneous, but the most abundant transcript includes a 5'-untranslated region of 30 nucleotides. When fused to the luciferase reporter gene, the 3.5-kilobase 5'-flanking region of the gene directed the expression of the heterologous protein selectively in differentiated Sol8 cells and transgenic mice, recapitulating the pattern of expression of the endogenous gene. Deletion analysis identified a 300-bp fragment sufficient to direct the myotube-specific expression of luciferase in Sol8 cells. The region lacks an apparent TATA element, and sequence motifs predicted to bind NRF-1, NRF-2, ox-box, or PPAR factors known to regulate other nuclear genes encoding mitochondrial proteins are not evident. Mutational analysis, however, identified two cis-elements necessary for the high level expression of the reporter protein: a MEF2 consensus element at -90 to -81 bp and an E-box element at -147 to -142 bp. Additional E-box motifs at closely located positions were mutated without loss of transcriptional activity. The dependence of transcriptional activation of cytochrome c oxidase VIaH on cis-elements similar to those found in contractile protein genes suggests that the striated muscle-specific expression is coregulated by mechanisms that control the lineage-specific expression of several contractile and cytosolic proteins.

Non-NASA Center↗
NASA NTRSDate not supplied

Sampling the ENSO response to tropical volcanic eruptions in the GISS-E2-1 model: physical & biogeochemical ocean effects

Despite observational evidence that an El-Niño is likely to follow tropical volcanic eruptions (Predybaylo et al, 2017), modelling studies have so far reached no consensus on either the sign or physical mechanism of El Niño response to volcanism (Khodri et al, 2017) . A previous modelling study found that following the Pinatubo eruption, the tropical Pacific developed El Niño-like conditions that triggered a decrease in the upwelling of DIC and increased carbon uptake (Eddebbar et al., 2019). However, the carbon cycle response to volcanisms as it depends on ENSO phase remains unclear. Here we perform thirty ensemble control simulations using the GISS-E2-1-G model to sample the pre-industrial control ENSO cycle and thirty more to superimpose a Pinatubo-like volcanic eruption. We find that the model tends to favor the development of a weak El-Niño following the volcanic eruption only in the case of a volcano that erupts at the start of a neutral ENSO phase. In response to the weak El-Niño, some anomalies have the same sign as those that develop from a strong El-Niño, such as weaker winds, shallower mixed layer depths, less direct but more diffuse radiation at the surface of the ocean, less nitrate, and lower primary productivity. However, other anomalies show the opposite sign as those from a strong El-Niño, such as more precipitation, less surface DIC, and less surface ocean pCO 2 . In contrast to the neutral phase, the volcanic response during positive ENSO and negative ENSO phases are swamped by the model’s internal variability.

ENSO↗
NASA NTRS2013

Flight Crew Workload, Acceptability, and Performance When Using Data Comm in a High-Density Terminal Area Simulation

This document describes a collaborative FAA/NASA experiment using 22 commercial airline pilots to determine the effect of using Data Comm to issue messages during busy, terminal area operations. Four conditions were defined that span current day to future flight deck equipage: Voice communication only, Data Comm only, Data Comm with Moving Map Display, and Data Comm with Moving Map displaying taxi route. Each condition was used in an arrival and a departure scenario at Boston Logan Airport. Of particular interest was the flight crew response to D-TAXI, the use of Data Comm by Air Traffic Control (ATC) to send taxi instructions. Quantitative data was collected on subject reaction time, flight technical error, operational errors, and eye tracking information. Questionnaires collected subjective feedback on workload, situation awareness, and acceptability to the flight crew for using Data Comm in a busy terminal area. Results showed that 95% of the Data Comm messages were responded to by the flight crew within one minute and 97% of the messages within two minutes. However, post experiment debrief comments revealed almost unanimous consensus that two minutes was a reasonable expectation for crew response. Flight crews reported that Expected D-TAXI messages were useful, and employment of these messages acceptable at all altitude bands evaluated during arrival scenarios. Results also indicate that the use of Data Comm for all evaluated message types in the terminal area was acceptable during surface operations, and during arrivals at any altitude above the Final Approach Fix, in terms of response time, workload, situation awareness, and flight technical performance. The flight crew reported the use of Data Comm as implemented in this experiment as unacceptable in two instances: in clearances to cross an active runway, and D-TAXI messages between the Final Approach Fix and 80 knots during landing roll. Critical cockpit tasks and the urgency of out-the window scan made the additional head down time to respond to Data Comm messages undesirable during these events. However, most crews also stated that Data Comm messages without an accompanying audio chime and no expectation of an immediate response could be acceptable even during these events.

Norman, R. Michael↗
NASA NTRS2018

Alignment and Bonding of Silicon Mirrors for High-Resolution Astronomical X-Ray Optics [10699-141]

Future large x-ray astronomy missions require large area and high resolution. The present consensus is to integrate thin, lightweight, segmented mirrors to form a compact but large telescope with high resolution (better than 1 sec). Key technologies: 1) Accurate mirror substrates: polishing high quality mono-crystalline silicon. 2) Stress-free reflective coating: stress-based distortion cancellation. 3) Precise alignment and integration: kinematic mounting and distortion-free bonding. Four-point alignment for quasi-cylindrically symmetric mirrors (segments) - 4-Point alignment: Pitch and yaw angles, image center (X, Y) are controlled by heights of the 4 mount points; Alignment Precision: better than 1 sec; Bonding error: approx. 0.1 micrometers (approx. 1 sec); Current single mirror pair x-ray tested: 3 sec (Half-Power Diameter). Integration into (meta) shell: Shell structure has rotationally defined axis; Interlocking mirrors means lightweight, mechanically strong telescope.

Chan, Kai-Wing↗
NASA NTRS2022

Process-Oriented Analysis of Dominant Sources of Uncertainty in the Land Carbon Sink

The observed global net land carbon sink is captured by current land models. All models agree that atmospheric CO 2 and nitrogen deposition driven gains in carbon stocks are partially offset by climate and land-use and land-cover change (LULCC) losses. However, there is a lack of consensus in the partitioning of the sink between vegetation and soil, where models do not even agree on the direction of change in carbon stocks over the past 60 years. This uncertainty is driven by plant productivity, allocation, and turnover response to atmospheric CO 2 (and to a smaller extent to LULCC), and the response of soil to LULCC (and to a lesser extent climate). Overall, differences in turnover explain ~70% of model spread in both vegetation and soil carbon changes. Further analysis of internal plant and soil (individual pools) cycling is needed to reduce uncertainty in the controlling processes behind the global land carbon sink.

Attribution↗
NASA NTRSDate not supplied

NSCOR for Evaluating Risk Factors and Biomarkers for Adaptation and Resilience to Spaceflight: Emotional Valence and Social Processes in ICC/ICE Environments

Space exploration class missions, such as a mission to Mars, will require optimization of human performance, adaptability, and resilience. This NASA Specialized Center of Research (NSCOR) utilizes the NIMH Research Domain Criteria (RDoC) framework to identify biological and behavioral markers of individual social adaptation and emotional resilience (as well as vulnerability) to spaceflight-relevant stressors such as living in extended isolation. The overarching goal of this NSCOR is to obtain novel information to help identify biomarkers of individuals who are resilient and/or adaptable to the stressors of isolated, confined, and controlled (ICC) and isolated, confined, and extreme (ICE) environments.A total of N=90 healthy adult astronaut surrogates are being studied in three spaceflight-analog environments: (1) n=40 healthy adults in the Isolation and Confinement Analog Research Unit (ICARUS), an ICC at the University of Pennsylvania, during 7-day missions, for a target total of 280 subject days; (2) n=32 healthy adult astronaut surrogates studied in NASA’s Human Exploration Research Analog (HERA), an ICC at Johnson Space Center during 45-day missions, for a target total of 2,112 subject days; and (3) n=18 healthy adults in the Alfred-Wegener-Institute’s Neumayer Station III, an ICE in Antarctica, during 14-month missions, for a target total of 7,560 subject days. Dr. Nindl’s Laboratory at the University of Pittsburgh is analyzing a priori selected protein biomarkers in blood, saliva, and urine. Complementary rodent models of exposure to early life stressors, confinement, and isolation are being evaluated at Dr. Hensch’s Laboratory to further validate the neurobehavioral and biological findings from the human studies.Given the inconsistency and varied definition of resilience/adaptation in the scientific literature, the NSCOR team developed a composite resilience/adaptation measure that reflects the most relevant outcomes to resilience/adaptation across psychosocial and neurobehavioral functions, as well as neurocognitive and spaceflight-relevant operational performance. To achieve this, group consensus was attained from subject matter experts to produce a rank-order of importance for each input variable. The final resilience/adaptation score included 36 variables that were collected across spaceflight analogs. As of 10/1/2021, the NSCOR project acquired data on n=27 subjects at ICARUS, n=16 at HERA, and n=18 at Neumayer. The COVID-19 pandemic delayed data acquisition at ICARUS and HERA.Among subjects studied to date, 99% of neural and neurobehavioral data (e.g., neuroimaging for structure and function, behavioral measures) as well as blood, saliva, and urine for biochemical assays have been acquired. For rodent models, Dr. Hensch’s laboratory has established biochemical and behavioral parameters reflecting confinement stress in social networks of mice for comparison to stress responses in the human spaceflight analog environments.Group social behaviors were measured with a Social Network Analysis (SNA) approach to define objective parameters associated with sociability and its plasticity by sex. This analytic approach may help identify a network of individuals who are more effective teammates or more likely to generate new social relationships. Data acquisition, biomarker assessment, and data quality control will continue through September 2022.

D F Dinges↗
NASA NTRS2002

The nature of the autonomic dysfunction in multiple system atrophy

The concept that multiple system atrophy (MSA, Shy-Drager syndrome) is a disorder of the autonomic nervous system is several decades old. While there has been renewed interest in the movement disorder associated with MSA, two recent consensus statements confirm the centrality of the autonomic disorder to the diagnosis. Here, we reexamine the autonomic pathophysiology in MSA. Whereas MSA is often thought of as "autonomic failure", new evidence indicates substantial persistence of functioning sympathetic and parasympathetic nerves even in clinically advanced disease. These findings help explain some of the previously poorly understood features of MSA. Recognition that MSA entails persistent, constitutive autonomic tone requires a significant revision of our concepts of its diagnosis and therapy. We will review recent evidence bearing on autonomic tone in MSA and discuss their therapeutic implications, particularly in terms of the possible development of a bionic baroreflex for better control of blood pressure.

NASA Discipline Regulatory Physiology↗
NASA NTRS1997

Clinical utility of T-wave alternans

Electrical alternans represents a variation in the morphology of electrocardiographic complexes on an every-other-beat basis in an ABABAB... pattern. Apparent electrical alternans associated with pericardial effusion results from rotation of the heart in the pericardial sac, and not true alternation in electrical conduction patterns. In contrast, true electrical alternans results from an alternation in electrical conduction patterns in the heart itself. Repolarization alternans is true electrical alternans associated with the ST segment and T wave of the electrocardiogram (ECG). Here we will focus on T-wave alternans (TWA) and its association with susceptibility to ventricular tachyarrhythmias. Electrical alternans was reported in the literature as early as 1909. Historically, electrical alternans has been regarded as a fairly rare electrocardiographic abnormality. Case reports of electrical alternans have been associated with a variety of disease states, including acute ischemia, Prinzmetal's angina, a variety of electrolyte abnormalities, and the long QT syndrome. Interestingly, patients born with the prolonged QT syndrome have a very high incidence of sudden cardiac death at an early age. Schwartz and Malliani showed that patients with the prolonged QT syndrome who do not demonstrate alternans at rest, may evidence alternans during stress such as emotional excitement. Thus, over the years electrical alternans has been associated anecdotally with conditions associated with an increased risk of ventricular arrhythmias. In 1948, Kalter reviewed the world literature on electrical alternans and found a total of 41 reported cases. In addition, he reviewed clinical ectrocardiograms from 6059 patients and found five new cases (incidence of less than 1 in 1000 patients). Interestingly, he found a very high mortality, 62%, associated with this condition. Despite the clinical associations reported in the literature, the consensus view of electrical alternans until recent years has been that alternans is an electrocardiographic curiosity rarely encountered in clinical practice which, when identified, does not have specific clinical significance.

Review, Tutorial↗
NASA NTRS1987

On the global mean structure of the thermosphere

A self-consistent model of the global mean structure of the thermosphere is used to examine the ionospheric and thermospheric processes that control the structure of the thermosphere for solar minimum and maximum conditions during geomagnetic quiet periods. The model includes the physical and chemical processes believed to be dominant in the thermosphere and ionosphere. The total solar energy input available in the extreme ultraviolet and in the Schumann-Runge continuum portion of the solar spectrum is 14.1 x 10 to the 11th W and 21.5 x 10 to the 11th W for solar minumum and maximum, respectively. The calculated exospheric temperature is too small if maintained only by radiative processes, and an auroral heat source is necessary to bring the calculated global mean structure into agreement with the MSIS-83 empirical model for both solar minimum and maximum conditions. These results support the consensus that there is high-latitude heat source present at all times.

Roble, R. G.↗
NASA NTRS1998

Space Solar Power Technical Interchange Meeting 2: SSP TIM 2

The 2nd Space Solar Power Technical Interchange Meeting (SSP TIM 2) was conducted September 21st through 24th with the first part consisting of a Plenary session. The summary results of this Plenary session are contained in part one of this report. The attendees were then organized into Working Breakout Sessions and Integrated Product Team (IPT) Sessions for the purpose of conducting in-depth discussions in specific topic areas and developing a consensus as to appropriate study plans and actions to be taken. The Second part covers the Plenary Summary Session, which contains the summary results of the Working Breakout Sessions and IPT Sessions. The appendix contains the list of attendees. The ob'jective was to provide an update for the study teams and develop plans for subsequent study activities. This SSP TIM 2 was initiated and the results reported electronically over the Internet. The International Space Station (ISS) could provide the following opportunities for conducting research and technology (R&T) which are applicable to SSP: (1) Automation and Robotics, (2) Advanced Power Generation, (3) Advanced Power Management & Distribution (PMAD), (4) Communications Systems and Networks, (5) Energy Storage, (6) In Space Propulsion (ISP), (7) Structural Dynamics and Control, and Assembly and (8) Wireless Power Transmission.

Sanders, Jim↗
NASA NTRS2009

Observations of Crew Dynamics During Mars Analog Simulations

Crewmembers on Mars missions will face new and unique challenges compared to those in close communications proximity to Mission Control centers. Crews on Mars will likely become more autonomous and responsible for their day-to-day planning. These explorers will need to make frequent real time decisions without the assistance of large ground support teams. Ground-centric control will no longer be an option due to the communications delays. As a result of the new decision making model, crew dynamics and leadership styles of future astronauts may become significantly different from the demands of today. As a volunteer for the Mars Society on two Mars analog missions, this presenter will discuss observations made during isolated, surface exploration simulations. The need for careful crew selections, not just based on individual skill sets, but on overall team interactions becomes apparent very quickly when the crew is planning their own days and deciding their own priorities. Even more important is the selection of a Mission Commander who can lead a team of highly skilled individuals with strong and varied opinions in a way that promotes crew consensus, maintains fairness, and prevents unnecessary crew fatigue.

Cusack, Stacy L.↗
NASA NTRS1997

Reference Model for an Open Archival Information System

This document is a technical report for use in developing a consensus on what is required to operate a permanent, or indefinite long-term, archive of digital information. It may be useful as a starting point for a similar document addressing the indefinite long-term preservation of non-digital information. This report establishes a common framework of terms and concepts which comprise an Open Archival Information System (OAIS). It allows existing and future archives to be more meaningfully compared and contrasted. It provides a basis for further standardization of within an archival context and it should promote greater vendor awareness of, and support of , archival requirements. Through the process of normal evolution, it is expected that expansion, deletion, or modification to this document may occur. This report is therefore subject to CCSDS document management and change control procedures.

Source record↗
NASA NTRS2019

Micrometeoroid Events in LISA Pathfinder

The zodiacal dust complex, a population of dust and small particles that pervades the solar system, provides important insight into the formation and dynamics of planets, comets, asteroids, and other bodies. We present a new set of data obtained from direct measurements of momentum transfer to a spacecraft from individual particle impacts. This technique is made possible by the extreme precision of the instruments flown on the LISA Pathfinder spacecraft, a technology demonstrator for a future space-based gravitational wave observatory. Pathfinder employed a technique known as drag-free control that achieved rejection of external disturbances, including particle impacts, using a micropropulsion system. Using a simple model of the impacts and knowledge of the control system, we show that it is possible to detect impacts and measure properties such as the transferred momentum, direction of travel, and location of impact on the spacecraft. In this paper, we present the results of a systematic search for impacts during 4348 hr of Pathfinder data. We report a total of 54 candidates with transferred momenta ranging from 0.2 to 230 μNs. We furthermore make a comparison of these candidates with models of micrometeoroid populations in the inner solar system, including those resulting from Jupiter-family comets (JFCs), Oort Cloud comets, Halley-type comets, and asteroids. We find that our measured population is consistent with a population dominated by JFCs, with some evidence for a smaller contribution from Halley-type comets, in agreement with consensus models of the zodiacal dust complex in the momentum range sampled by LISA Pathfinder.

Thorpe, J. I.↗
NASA NTRS1991

Guideline requirements for serviceable spacecraft grasping/berthing/docking interfaces based on simulations and flight experience (survey paper)

As space vehicles and structures become larger and more complex, the development of systems to assist humans in assembling, operating, maintaining, and performing space rescue or retrieval of these vehicles and structures becomes increasingly important. With the diversity of international spacecraft, both manned and unmanned, planned to be in orbit in the future, a set of guidelines for berthing and docking subsystems is mandatory if servicing, resupply, and retrieval is to become practical on an international level. Successful interaction between these space systems and ground and/or space-based humans requires standardized and effective operational interface designs, particularly with respect to space grasping/berthing/docking interface mechanisms. This paper defines the spacecraft mechanical interfaces necessary to create a standard dynamic envelope for joining two free-flying spacecraft in a 'hard' berth or dock with each other in space. A review was made of past space flights and dynamics simulations dating back to 1962 to obtain necessary parameters and their values for successful manually controlled and autonomous spacecraft docking/berthing. The various spacecraft docking/berthing mechanisms and concepts are illustrated along with their dynamic capture and impact tolerances including maximum contact velocity along the approach axis and in the y-z plane; capture linear misalignment tolerances; and maximum capture roll, pitch, and yaw angles. From this data sets of recommended guidelines parameters were developed for autonomous and manual impact docking tolerances, non-impact grasping/berthing tolerances (end effectors), berthing contact conditions, and alignment tolerances after rigidizing. Also, detailed requirements were developed for mechanical design interface features, as well as latching, unlatching, and separation tolerances. This data was drafted in the form of a proposed ANSI Standard guideline, reviewed, and added to by members of the committee representing several spacecraft manufacturers, NASA, and the USAF, and a consensus was reached.

Thompson, Allen B.↗
NASA NTRS2020

ISMIP6 Antarctica: A Multi-Model Ensemble of the Antarctic Ice Sheet Evolution Over the 21st Century

Ice flow models of the Antarctic ice sheet are commonly used to simulate its future evolution in response to different climate scenarios and assess the mass loss that would contribute to future sea level rise. However, there is currently no consensus on estimates of the future mass balance of the ice sheet, primarily because of differences in the representation of physical processes, forcings employed and initial states of ice sheet models. This study presents results from ice flow model simulations from 13 international groups focusing on the evolution of the Antarctic ice sheet during the period 2015–2100 as part of the Ice Sheet Model Intercomparison for CMIP6 (ISMIP6). They are forced with outputs from a subset of models from the Coupled Model Intercomparison Project Phase 5 (CMIP5), representative of the spread in climate model results. Simulations of the Antarctic ice sheet contribution to sea level rise in response to increased warming during this period varies between -7:8 and 30.0 cm of sea level equivalent (SLE) under Representative Concentration Pathway (RCP) 8.5 scenario forcing. These numbers are relative to a control experiment with constant climate conditions and should therefore be added to the mass loss contribution under climate conditions similar to present-day conditions over the same period. The simulated evolution of the West Antarctic ice sheet varies widely among models, with an overall mass loss, up to 18.0 cm SLE, in response to changes in oceanic conditions. East Antarctica ass change varies between -6.1 and 8.3 cm SLE in the simulations, with a significant increase in surface mass balance outweighing the increased ice discharge under most RCP 8.5 scenario forcings. The inclusion of ice shelf collapse, here assumed to be caused by large amounts of liquid water ponding at the surface of ice shelves, yields an additional simulated mass loss of 28mm compared to simulations without ice shelf collapse. The largest sources of uncertainty come from the climate forcing, the ocean-induced melt rates, the calibration of these melt rates based on oceanic conditions taken outside of ice shelf cavities and the ice sheet dynamic response to these oceanic changes. Results under RCP 2.6 scenario based on two CMIP5 climate models show an additional mass loss of 0 and 3 cm of SLE on average compared to simulations done under present-day conditions for the two CMIP5 forcings used and display limited mass gain in East Antarctica.

Hélène Seroussi↗
NASA NTRS1997

17beta-estradiol potently suppresses cAMP-induced insulin-like growth factor-I gene activation in primary rat osteoblast cultures

Insulin-like growth factor-I (IGF-I) is a key factor in bone remodeling. In osteoblasts, IGF-I synthesis is enhanced by parathyroid hormone and prostaglandin E2 (PGE2) through cAMP-activated protein kinase. In rats, estrogen loss after ovariectomy leads to a rise in serum IGF-I and an increase in bone remodeling, both of which are reversed by estrogen treatment. To examine estrogen-dependent regulation of IGF-I expression at the molecular level, primary fetal rat osteoblasts were co-transfected with the estrogen receptor (hER, to ensure active ER expression), and luciferase reporter plasmids controlled by promoter 1 of the rat IGF-I gene (IGF-I P1), used exclusively in these cells. As reported, 1 microM PGE2 increased IGF-I P1 activity by 5-fold. 17beta-Estradiol alone had no effect, but dose-dependently suppressed the stimulatory effect of PGE2 by up to 90% (ED50 approximately 0.1 nM). This occurred within 3 h, persisted for at least 16 h, required ER, and appeared specific, since 17alpha-estradiol was 100-300-fold less effective. By contrast, 17beta-estradiol stimulated estrogen response element (ERE)-dependent reporter expression by up to 10-fold. 17beta-Estradiol also suppressed an IGF-I P1 construct retaining only minimal promoter sequence required for cAMP-dependent gene activation, but did not affect the 60-fold increase in cAMP induced by PGE2. There is no consensus ERE in rat IGF-I P1, suggesting novel downstream interactions in the cAMP pathway that normally enhances IGF-I expression in skeletal cells. To explore this, nuclear extract from osteoblasts expressing hER were examined by electrophoretic mobility shift assay using the atypical cAMP response element in IGF-I P1. Estrogen alone did not cause DNA-protein binding, while PGE2 induced a characteristic gel shift complex. Co-treatment with both hormones caused a gel shift greatly diminished in intensity, consistent with their combined effects on IGF-I promoter activity. Nonetheless, hER did not bind IGF-I cAMP response element or any adjacent sequences. These results provide new molecular evidence that estrogen may temper the biological effects of hormones acting through cAMP to regulate skeletal IGF-I expression and activity.

Non-NASA Center↗