Search NASA⌕ Search

SEARCH · Search NASA

Results for “Estrogen”

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.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2019

Oil Dispersant Corexit 9500 Is Weakly Estrogenic, but Does Not Skew the Sex Ratio in Alligator Mississippiensis

During the Deepwater Horizon oil spill, vast quantities of the chemical dispersant Corexit 9500 were applied in remediation efforts. In addition to the acute toxicity and obesogenicity of Corexit, it is important to further evaluate Corexit with long-term sublethal endocrine endpoints. The American alligator (Alligator mississippiensis) exhibits temperature-dependent sex determination, in which egg incubation temperatures during a thermosensitive period (TSP) in embryonic development determine sex of the embryos. Estrogen signals also play critical roles in this process. For example, a single exposure to exogenous estrogen during the TSP overrides the effects of temperature and leads to skewed sex ratios. At a dose of 100 ppm, Corexit significantly induced transcriptional activity of both alligator nuclear estrogen receptors 1 and 2 in vitro using the reporter gene assays. To investigate the estrogenic effects on gonadal development in ovo, alligator eggs were exposed to Corexit at environmentally relevant concentrations (0.25, 2.5, and 25 ppm) prior to the TSP. Significant delays in the hatching and growth were observed in 0.25 and 25 ppm Corexit exposed groups. At one week of age, no significant effects on sex ratios or testicular mRNA abundance were observed as a result of exposure to Corexit at the tested exposure levels, suggesting Corexit does not have strong estrogenic activity in ovo. Further investigations are required using individual components of Corexit to better understand their estrogenic effects on the development and reproductive health of alligators and other coastal aquatic wildlife.

Nicole Mcnabb↗
NASA NTRS1997

Effects of growth hormone and low dose estrogen on bone growth and turnover in long bones of hypophysectomized rats

Pituitary hormones are recognized as critical to longitudinal growth, but their role in the radial growth of bone and in maintaining cancellous bone balance are less clear. This investigation examines the histomorphometric effects of hypophysectomy (Hx) and ovariectomy (OVX) and the subsequent replacement of growth hormone (GH) and estrogen (E), in order to determine the effects and possible interactions between these two hormones on cortical and cancellous bone growth and turnover. The replacement of estrogen is of interest since Hx results in both pituitary and gonadal hormone insufficiencies, with the latter being caused by the Hx-associated reduction in follicle stimulating hormone (FSH). All hypophysectomized animals received daily supplements of hydrocortisone (500 microg/kg) and L-thyroxine (10 microg/kg), whereas intact animals received daily saline injections. One week following surgery, hypophysectomized animals received either daily injections of low-dose 17 beta-estradiol (4.8 microg/kg s.c.), 3 X/d recombinant human GH (2 U/kg s.c.), both, or saline for a period of two weeks. Flurochromes were administered at weekly intervals to label bone matrix undergoing mineralization. Whereas Hx resulted in reductions in body weight, uterine weight, and tibial length, OVX significantly increased body weight and tibial length, while reducing uterine weight. The combination of OVX and Hx resulted in values similar to Hx alone. Treatment with GH normalized body weight and bone length, while not affecting uterine weight in hypophysectomized animals. Estrogen increased uterine weight, while not impacting longitudinal bone growth and reduced body weight. Hypophysectomy diminished tibial cortical bone area through reductions in both mineral appositional rate (MAR) and bone formation rate (BFR). While E had no effect, GH increased both MAR and BFR, though not to sham-operated (control) levels. Hypophysectomy reduced proximal tibial trabecular number and cancellous bone area, and increased trabecular separation. Both GH and E reduced cancellous osteopenia, although employing different mechanisms. GH reduced the decrease in trabecular thickness, whereas E reduced the decrease in trabecular number and the increase in trabecular separation. Hypophysectomy reduced both Tb.MAR and Tb.BFR while treatment with GH enhanced them. This investigation has shown that Hx and GH have a dramatic impact on selected static and dynamic indices of rat cortical and cancellous histomorphometry. Furthermore, the mechanisms of action of GH and E differ, and suggest that some of the skeletal changes associated with Hx are caused by deficiencies in estrogen as well as deficiencies in growth hormone.

NASA Discipline Regulatory Physiology↗
NASA NTRS1997

Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain

Estrogen deficiency induced bone loss is associated with increased bone turnover in rats and humans. The respective roles of increased bone turnover and altered balance between bone formation and bone resorption in mediating estrogen deficiency-induced cancellous bone loss was investigated in ovariectomized rats. Ovariectomy resulted in increased bone turnover in the distal femur. However, cancellous bone was preferentially lost in the metaphysis, a site that normally experiences low strain energy. No bone loss was observed in the epiphysis, a site experiencing higher strain energy. The role of mechanical strain in maintaining bone balance was investigated by altering the strain history. Mechanical strain was increased and decreased in long bones of ovariectomized rats by treadmill exercise and functional unloading, respectively. Functional unloading was achieved during orbital spaceflight and following unilateral sciatic neurotomy. Increasing mechanical loading reduced bone loss in the metaphysis. In contrast, decreasing loading accentuated bone loss in the metaphysis and resulted in bone loss in the epiphysis. Finally, administration of estrogen to ovariectomized rats reduced bone loss in the unloaded and prevented loss in the loaded limb following unilateral sciatic neurotomy in part by reducing indices of bone turnover. These results suggest that estrogen regulates the rate of bone turnover, but the overall balance between bone formation and bone resorption is influenced by prevailing levels of mechanical strain.

STS-62 Shuttle Project↗
NASA NTRS1980

Hypergravity and estrogen effects on avian anterior pituitary growth hormone and prolactin levels

Developing female chicks with fractured right radii were maintained for 14 d at either earth gravity (1 g) or a hypergravity state (2 g). The birds at 1 g were divided into groups which received daily injections of (1) saline, (2) 200 micrograms estrone, and (3) 400 micrograms estrone for 14 d. The 2-g birds were divided into three similarly treated groups. All 2-g birds showed significantly lower body weights than did 1-g birds. Anterior pituitary (AP) glands were excised and analyzed for growth hormone and prolactin content by analytical electrophoresis. The 1-g chicks receiving either dose of daily estrogen showed increased AP growth hormone levels, whereas hypergravity alone did not affect growth hormone content. Chicks exposed to daily estrogen and hypergravity displayed reduced growth hormone levels. AP prolactin levels were slightly increased by the lower daily estrogen dose in 1-g birds, but markedly reduced in birds exposed only to hypergravity. Doubly-treated chicks displayed normal prolactin levels. Reduced growth in 2-g birds might be due, in part, to reduced AP levels of prolactin and/or growth hormone.

Fiorindo, R. P.↗
NASA NTRS1988

Changes in plasma volume during bed rest - Effects of menstrual cycle and estrogen administration

The effect of increased blood estrogen concentration, caused either during normal menstrual cycles or by exogenous administration of premarin, on the bed-rest (BR) induced decrease in plasma volume (PV) was investigated. In women who underwent duplicate 11-day BR without estrogen supplementation, the PV was found to decrease significantly, during the first 5 days of BR, to a lower level at which it remained for the rest of the BR period. In women who began BR in the periovulatory stage of the menstrual cycle, the loss of PV was delayed, while women who began BR during other stages of the cycle exhibited the usual trend of the PV decrease during the BR. In women who underwent a single 12-day BR period while taking premarin (1.25 mg/day), PV was found to decrease during the first 4-5 days of BR, but then returned toward the pre-BR level during the remainder of the BR, indicating that estrogens have a role in stabilizing body fluid volume.

Fortney, S. M.↗
NASA NTRS2004

Decreased Estrogen May Contribute to Osteopenia in Unloaded Bones

Progressive loss of weight-bearing bone in astronauts is one of the most serious impediments to long-duration spaceflight. Estrogen deficiency in women is an established factor in bone loss. Reduced sex hormone levels have been reported in male astronauts, but no data is available regarding spaceflight effects on female sex hormones. The objective of our study was to determine the role of estrogen in disuse osteopenia. The NASA developed hindlimb suspension (HLS) model was used to simulate the unloading disuse of weight-bearing bones experienced in space. Female Sprague-Dawley rats (age 77d; n = 20/group) were HLS or kept ambulatory (AMB) for 38 d and endocrine and bone indices determined. HLS of rats resulted in lower (p less than 0.01) bone mass (9%0), bone mineral content (BMC 13%) and mechanical strength (28%) compared to AMB animals. Plasma estradiol (E2) was lower (p = 0.03) in HLS (10.1 +/- 1.4 pg/ml) compared to AMB rats (16.7 +/- 2.6 pg/ml). E2 was positively correlated to BMC r(sup 2) = 0.67 and mechanical strength r(sup 2) = 0.61. These results suggest that reduced E2 plays a role in disuse osteopenia induced by HLS. Plasma or pituitary lutenizing hormone (LH) and follicle stimulating hormone (FSH) levels were not different in HLS versus AMB rats. However, pituitary LH was correlated to E2 (r(sup 2) = 0.57), suggesting changes in E2 were exerted at the level of the hypothalamus-pituitary axis. Understanding the role of estrogen in disuse osteopenia is necessary to the development of efficacious therapies for female astronauts, bed rest patients and the increasing number of individuals in our sedentary population suffering bone loss.

Tou, Janet↗
NASA NTRS2002

Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats

We hypothesized that estradiol treatment would improve vascular dysfunction commonly associated with obesity, hyperlipidemia, and insulin resistance. A sham operation or 17beta-estradiol pellet implantation was performed in male lean and obese Zucker rats. Maximal vasoconstriction (VC) to phenylephrine (PE) and potassium chloride was exaggerated in control obese rats compared with lean rats, but estradiol significantly attenuated VC in the obese rats. Estradiol reduced the PE EC50 in all groups. This effect was cyclooxygenase independent, because preincubation with indomethacin reduced VC response to PE similarly in a subset of control and estrogen-treated lean rats. Endothelium-independent vasodilation (VD) to sodium nitroprusside was similar among groups, but endothelium-dependent VD to ACh was significantly impaired in obese compared with lean rats. Estradiol improved VD in lean and obese rats by decreasing EC50 but impaired function by decreasing maximal VD. The shift in EC50 corresponded to an upregulation in nitric oxide synthase III protein expression in the aorta of the estrogen-treated obese rats. In summary, estrogen treatment improves vascular function in male insulin-resistant, obese rats, partially via an upregulation of nitric oxide synthase III protein expression. These effects are counteracted by adverse factors, such as hyperlipidemia and, potentially, a release of an endothelium-derived contractile agent.

Non-NASA Center↗
DOE OSTI2023

Structural Determinants of the Binding and Activation of Estrogen Receptor α by Phenolic Thieno[2,3- d ]pyrimidines

Synthetic, structural, and computational approaches were used to solve the puzzle as to how a phenolic nonsteroidal estrogen 1 with only a single H-bond to its receptor was more potent than an isomer 2 which formed an intricate network of H-bonds. Synthesis of a series of substituted phenols revealed that pK a was not a determinant of estrogenic activity. First-principles calculation also failed to explain the difference in activity of 1 and 2. Molecular dynamics revealed that 1 formed a more stable receptor complex compared to 2, which may explain its increased activity despite forming fewer apparent H-bonds with the protein.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Towards replacement of animal tests with in vitro assays: a gene expression biomarker predicts in vitro and in vivo estrogen receptor activity

High-throughput transcriptomics (HTTr) has the potential to support efforts to reduce or replace some animal tests. In past studies, we described a computational approach utilizing a gene expression biomarker consisting of 46 genes to predict estrogen receptor (ER) activity after chemical exposure in ER-positive human breast cancer cells including the MCF-7 cell line. We hypothesized that the biomarker model could identify ER activities of chemicals examined by Endocrine Disruptor Screening Program (EDSP) Tier 1 screening assays in which transcript profiles of the same chemicals were examined in MCF-7 cells. For the 62 chemicals examined including 5 chemicals examined in this study using RNA-Seq, the ER biomarker model accuracy was 1) 97% for in vitro reference chemicals, 2) 76–85% for guideline uterotrophic assays, and 3) 87–88% for guideline and nonguideline uterotrophic assays. For the same chemicals, these accuracies were similar or slightly better than those of the ToxCast ER model based on 18 in vitro assays. The performance of the ER biomarker model indicates that HTTr interpreted using the ER biomarker correctly identifies active and inactive ER reference chemicals. Finally, as part of the HTTr screening program the approach could rapidly identify chemicals with potential ER bioactivities for additional screening and testing.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Natural colloids facilitated transport of steroidal estrogens in saturated porous media: Mechanism and processes

Steroid estrogens (SEs) are widely distributed in terrestrial environment, whilst the transport of SEs in groundwater is not well understood. Specifically, the effects of ubiquitous natural colloids on the SEs transport are unclear. Here, the influence of inorganic colloids (i.e. silica and illite) and organic colloids, i.e. Humic acid (HA), on the transport of estrone (E1) and estradiol (E2) in saturated porous media were studied in laboratory scale column experiments. Characterization on the colloids and the column packing material was conducted to provide bases for the interpretation of column test findings. Results showed that the transport of SEs was facilitated by the nature colloids that were migrating through the saturated porous media. About 38.5% of E1 and 24.6% of E2 were retained in the column when colloids were absent in the system. Further, when transporting with silica colloids, illite colloids, and HA colloids, the transport of E1 was enhanced by 15.64%, 11.17%, and 25.60%, respectively; whilst the transport of E2 was improved by 19.56%, 23.06%, and 36.40%, respectively. The colloids’ SEs transport enhancement depended not only on the mobility of the colloids but also on their geochemical characteristics. The tested organic colloids showed 1.5-2.5 times greater ability on promoting the transport of SEs than the inorganic ones. The proposed mechanisms of nature colloids facilitated transport of SEs include competing for adsorption sites on the sand surfaces by the colloids resulting mobilization of adsorbed SEs from solid matrix, and transport of colloids as carriers for SEs.

54 ENVIRONMENTAL SCIENCES↗
NASA NTRS1984

Androgen-estrogen synergy in rat levator ani muscle Glucose-6-phosphate dehydrogenase

The effects of castration and hormone administration on the activity of glucose-6-phosphate dehydrogenase in the rat levator ani muscle were studied. Castration caused a decrease in enzyme activity and in wet weight of the levator ani muscle. Chronic administration of testosterone propionate increased glucose-6-phosphate dehydrogenase activity in the levator ani muscle of castrated rats; the magnitude of the recovery of enzyme activity was related to the length of time of exposure to testosterone propionate after castration as well as to the length of time the animals were castrated. The longer the period of castration before exposure to testosterone propionate, the greater the effect. This result may be related to previously reported castration-mediated increases in androgen receptor binding in muscle. Dihydrotestosterone was less effective than testosterone propionate in enhancing glucose-6-phosphate dehydrogenase activity in the levator ani muscle from castrated rats; estradiol-17-beta alone was ineffective. Combined treatment with estradiol-17-beta and dihydrotestosterone, however, was as effective as testosterone alone. Thus, androgens and estrogens may exert synergistic effects on levator ani muscle.

Max, S. R.↗
DOE OSTI2024

G-protein coupled estrogen receptor 1, amyloid-β, and tau tangles in older adults

Accumulation of amyloid-β (Aβ) and tau tangles are hallmarks of Alzheimer’s disease. Aβ is extracellular while tau tangles are typically intracellular, and it is unknown how these two proteinopathies are connected. Here, we use data of 1206 elders and test that RNA expression levels of GPER1, a transmembrane protein, modify the association of Aβ with tau tangles. GPER1 RNA expression is related to more tau tangles (p = 0.001). Moreover, GPER1 expression modifies the association of immunohistochemistry-derived Aβ load with tau tangles (p = 0.044). Similarly, GPER1 expression modifies the association between Aβ proteoforms and tau tangles: total Aβ protein (p = 0.030) and Aβ38 peptide (p = 0.002). Using single nuclei RNA-seq indicates that GPER1 RNA expression in astrocytes modifies the relation of Aβ load with tau tangles (p = 0.002), but not GPER1 in excitatory neurons or endothelial cells. We conclude that GPER1 may be a link between Aβ and tau tangles driven mainly by astrocytic GPER1 expression.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

A Functional Survey of the Regulatory Landscape of Estrogen Receptor–Positive Breast Cancer Evolution

Abstract Only a handful of somatic alterations have been linked to endocrine therapy resistance in hormone-dependent breast cancer, potentially explaining ∼40% of relapses. If other mechanisms underlie the evolution of hormone-dependent breast cancer under adjuvant therapy is currently unknown. In this work, we employ functional genomics to dissect the contribution of cis-regulatory elements (CRE) to cancer evolution by focusing on 12 megabases of noncoding DNA, including clonal enhancers, gene promoters, and boundaries of topologically associating domains. Parallel epigenetic perturbation (CRISPRi) in vitro reveals context-dependent roles for many of these CREs, with a specific impact on dormancy entrance and endocrine therapy resistance. Profiling of CRE somatic alterations in a unique, longitudinal cohort of patients treated with endocrine therapies identifies a limited set of noncoding changes potentially involved in therapy resistance. Overall, our data uncover how endocrine therapies trigger the emergence of transient features which could ultimately be exploited to hinder the adaptive process. Significance: This study shows that cells adapting to endocrine therapies undergo changes in the usage or regulatory regions. Dormant cells are less vulnerable to regulatory perturbation but gain transient dependencies which can be exploited to decrease the formation of dormant persisters.

Oncology↗