Sex specific response of cultured human bone cells to ERα and ERβ specific agonists by modulation of cell proliferation and creatine kinase specific activity

Sömjen, Dalia; Katzburg, Sara; Sharon, Orli; Knoll, Esther; Hendel, David; Stern, Naftali

doi:10.1016/j.jsbmb.2011.03.006

Cited by 8 publications

(7 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also observed a correlation of serum oestrogen concentration with both the TFV and FTC reduction and the renal glomerular functional increase. We found that oestradiol does not affect the kinases that phosphorylate TFV in plasma and colon tissue, but this might have been the result of off‐setting decreases in plasma parent drug PK and increases in kinase effects (predicted by in vitro data) .…”

Section: Discussionmentioning

confidence: 74%

“…The activation of tenofovir (TFV) and emtricitabine (FTC) requires intracellular phosphorylation by different nucleotide kinases in different tissues. In cell culture, oestrogen increases the activity of creatine kinase, which phosphorylates TFV‐MP in colon cells . Cisgender female genital tract CD4 + cells shows decreased TFV‐diphosphate (TFV‐DP) concentrations in the presence of progesterone and oestradiol .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transgender women on oral HIV pre‐exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men

et al. 2019

View full text Add to dashboard Cite

Introduction Oral HIV Pre‐Exposure Prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate (TDF)/emtricitabine (FTC) is highly effective. Transgender women (TGW) have increased HIV risk, but have been underrepresented in trials. For TGW on oestrogens for gender‐affirming hormone treatment (GAHT), TDF/FTC‐oestrogen interactions may negatively affect HIV prevention or gender‐affirming goals. Our aim was to evaluate any pharmacokinetic drug‐drug interaction between GAHT and TDF/FTC. Methods We performed a pharmacokinetic study, in an urban outpatient setting in 2016 to 2018, of the effects of GAHT on TFV, FTC and the active forms TFV diphosphate (TFV‐DP) and FTC triphosphate (FTC‐TP) in eight TGW and eight cisgender men (CGM). At screening, participants were HIV negative. TGW were to maintain their GAHT regimens and have plasma oestradiol concentrations >100 pg/mL. Under direct observation, participants took oral TDF/FTC daily for seven days. At the last dose, blood was collected pre‐dose, one, two, four, six, eight and twenty‐four hours, and colon biopsies were collected at 24 hours to measure drug concentration. TGW versus CGM concentration comparisons used non‐parametric tests. Blood and colon tissue were also obtained to assess kinase expression. Results Plasma TFV and FTC C24 (trough) concentrations in TGW were lower by 32% (p = 0.010) and 32% (p = 0.038) respectively, when compared to CGM. Plasma TFV and FTC 24‐hr area under the concentration‐time curve in TGW trended toward and was significantly lower by 27% (p = 0.065) and 24% (p = 0.028) respectively. Peak plasma TFV and FTC concentrations, as well as all other pharmacokinetic measures, were not statistically significant when comparing TGW to CGM. Oestradiol concentrations were not different comparing before and after TDF/FTC dosing. Plasma oestrogen concentration, renal function (estimated creatinine clearance and glomerular filtration rate), and TFV and FTC plasma concentrations (trough and area under the concentration‐time curve) were all correlated. Conclusions GAHT modestly reduces both TFV and FTC plasma concentrations. In TGW taking GAHT, it is unknown if this reduction will impact the HIV protective efficacy of a daily PrEP regimen. However, the combination of an on demand (2 + 1 + 1) PrEP regimen and GAHT may result in concentrations too low for reliable prevention of HIV infection.

show abstract

Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Transgender women on oral HIV pre‐exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Because ERα activation with PPT has previously been reported to up-regulate ERβ expression in osteoblastic cells (36), we quantified ERβ expression as a positive control of PPT action and found it to be elevated at this time point (Fig. 4 C ).…”

Section: Resultsmentioning

confidence: 99%

“…However, the outcomes of ERβ signaling depend on the cellular context in which it operates; whereas ERβ largely inhibits transcriptomic changes caused by estrogen treatment when ERα is present, it promotes expression of a subset of genes when ERα is deleted (35). In osteoblastic cells, ERα activation increases ERβ expression (36) and has been shown to directly bind the ERβ promoter in other cell types (37). In contrast, ERβ can repress ERα expression (38), and mice lacking ERβ have increased ERα in their bones (39).…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor α Mediates Proliferation of Osteoblastic Cells Stimulated by Estrogen and Mechanical Strain, but Their Acute Down-regulation of the Wnt Antagonist Sost Is Mediated by Estrogen Receptor β

Galea

Meakin

Sugiyama

et al. 2013

Journal of Biological Chemistry

114

124

View full text Add to dashboard Cite

Background: Strain and estrogens down-regulate Sost/sclerostin and stimulate osteoblastic proliferation.Results: ERα inhibition prevents proliferation. ERβ inhibition prevents Sost down-regulation by strain or estradiol. Sclerostin prevents proliferation following strain and not estradiol.Conclusion: ERα promotes proliferation, and ERβ mediates Sost down-regulation following estradiol ligand stimulation and ligand independently following strain.Significance: Selective ER modulators could promote osteogenesis through differential regulation of Sost and proliferation.

show abstract

“…For instance, creatine kinase activity, which regulates the use and consumption of energy, increases and decreases in sync with the rat estrous cycle (Sömjen et al, 1991). Moreover, brain-type creatine kinase has been shown to be upregulated sex-specifically by estrogens in female rats and by testosterone in male rats (Malnick et al ., 1983; Sömjen et al ., 1989; 1997; 2011). Our previous forced swim data indicated that creatine supplementation produced antidepressant-like effects in females particularly during the proestrus and estrus phases of the estrous cycle, when levels of ovarian hormones are high (Allen et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats

Allen

DeBold

Rios

et al. 2015

Pharmacology Biochemistry and Behavior

View full text Add to dashboard Cite

Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism shown to improve depressive symptoms in humans and animals, especially in females. To better understand the pharmacological effects of creatine, we examined its influence on depression-related hippocampal gene expression and behaviors in the presence and absence of sex steroids. Sham-operated and gonadectomized male and female rats were fed chow alone or chow blended with either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open field, and wire suspension tests, or seven weeks total. Before supplementation, males were chronically implanted with an empty or a testosterone-filled (T) capsule (10-mm surface release), and females were administered progesterone (P, 250 μg), estradiol benzoate (EB, 2.5 μg), EB+P, or sesame oil vehicle weekly. Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B, doublecortin, calretinin, and calbindin, were downregulated in sham males given 4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in sham females given 4% creatine. In contrast, combined 4% creatine + T in castrates prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly, combined 4% creatine + EB+P in ovariectomized females attenuated downregulation of BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like behaviors were observed in EB+P-treated ovariectomized females fed creatine, with similar trends in T-treated castrates fed creatine. Altogether, these data show that chronic, high-dose creatine has opposing effects on neuroplasticity-related genes and depressive behavior in intact and gonadectomized male and female rats. The dose and schedule of creatine used negatively impacted hippocampal neuronal integrity in otherwise healthy brains, possibly through negative compensatory changes in energy metabolism, whereas combined creatine and sex steroids acted in a neuroprotective manner in gonadectomized rats, potentially by reducing metabolic complications associated with castration or ovariectomy.

show abstract

Sex specific response of cultured human bone cells to ERα and ERβ specific agonists by modulation of cell proliferation and creatine kinase specific activity

Cited by 8 publications

References 24 publications

Transgender women on oral HIV pre‐exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men

Transgender women on oral HIV pre‐exposure prophylaxis have significantly lower tenofovir and emtricitabine concentrations when also taking oestrogen when compared to cisgender men

Estrogen Receptor α Mediates Proliferation of Osteoblastic Cells Stimulated by Estrogen and Mechanical Strain, but Their Acute Down-regulation of the Wnt Antagonist Sost Is Mediated by Estrogen Receptor β

Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats

Contact Info

Product

Resources

About