ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2021
17α-Estradiol Modulates IGF1 and Hepatic Gene Expression in a Sex-Specific Manner.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- VCD-induced estropause fails to enhance responsiveness to 17α-estradiol in adult female mice.GeroScience · 2026Article
- 17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.Ageing research reviews · 2026Review
- Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17α-estradiol in middle-aged male mice.Communications medicine · 2025Article
- Canagliflozin treatment prevents follicular exhaustion and attenuates hallmarks of ovarian aging in genetically heterogenous mice.GeroScience · 2025Article
- Assessment of the Impact ofIranian journal of medical sciences · 2025Article
- Liver-specific actions of GH and IGF1 that protect against MASLD.Nature reviews. Endocrinology · 2025 · on this mapReview
- A pilot study evaluating dosing tolerability of 17α-estradiol in male common marmosets (Callithrix jacchus).GeroScience · 2025Article
- Systemic metabolic benefits of 17α-estradiol are not exclusively mediated by ERα in glutamatergic or GABAergic neurons.GeroScience · 2024Article
- 17α-Estradiol alleviates high-fat diet-induced inflammatory and metabolic dysfunction in skeletal muscle of male and female mice.American journal of physiology. Endocrinology and metabolism · 2024Article
- Responses to Many Anti-Aging Interventions Are Sexually Dimorphic.The world journal of men's health · 2024Review
- Assessing tolerability and physiological responses to 17α-estradiol administration in male rhesus macaques.GeroScience · 2023Article
- 17α-estradiol does not adversely affect sperm parameters or fertility in male mice: implications for reproduction-longevity trade-offs.GeroScience · 2023Article
- Metabolic benefits of 17α-estradiol in liver are partially mediated by ERβ in male mice.Scientific reports · 2023Article
- A Genetically Heterogeneous Rat Model with Divergent Mitochondrial Genomes.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Metabolic benefits of 17α-estradiol in liver are partially mediated by ERβ in male mice.bioRxiv : the preprint server for biology · 2023Article
- 17α-estradiol, a lifespan-extending compound, attenuates liver fibrosis by modulating collagen turnover rates in male mice.American journal of physiology. Endocrinology and metabolism · 2023Article
- Role of Estrogen Receptor α in Aging and Chronic Disease.Advances in geriatric medicine and research · 2023Article
- Mild calorie restriction, but not 17α-estradiol, extends ovarian reserve and fertility in female mice.Experimental gerontology · 2022Article
- In Vitro and In Vivo Wound Healing Activity ofAdvances in pharmacological and pharmaceutical sciences · 2022Article
- Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 4 countries.
Funding
Abstract
Aging is the greatest risk factor for most chronic diseases. The somatotropic axis is one of the most conserved biological pathways that regulates aging across species. 17α-Estradiol (17α-E2), a diastereomer of 17β-estradiol (17β-E2), was recently found to elicit health benefits, including improved insulin sensitivity and extend longevity exclusively in male mice. Given that 17β-E2 is known to modulate somatotropic signaling in females through actions in the pituitary and liver, we hypothesized that 17α-E2 may be modulating the somatotropic axis in males, thereby contributing to health benefits. Herein, we demonstrate that 17α-E2 increases hepatic insulin-like growth factor 1 (IGF1) production in male mice without inducing any changes in pulsatile growth hormone (GH) secretion. Using growth hormone receptor knockout (GHRKO) mice, we subsequently determined that the induction of hepatic IGF1 by 17α-E2 is dependent upon GH signaling in male mice, and that 17α-E2 elicits no effects on IGF1 production in female mice. We also determined that 17α-E2 failed to feminize the hepatic transcriptional profile in normal (N) male mice, as evidenced by a clear divergence between the sexes, regardless of treatment. Conversely, significant overlap in transcriptional profiles was observed between sexes in GHRKO mice, and this was unaffected by 17α-E2 treatment. Based on these findings, we propose that 17α-E2 acts as a pleiotropic pathway modulator in male mice by uncoupling IGF1 production from insulin sensitivity. In summary, 17α-E2 treatment upregulates IGF1 production in wild-type (and N) male mice in what appears to be a GH-dependent fashion, while no effects in female IGF1 production are observed following 17α-E2 treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.