De Novo Synthesized Estradiol: A Role in Modulating the Cerebellar Function.

Int J Mol Sci

Department of Experimental Medicine, Section of Physiology and Biochemistry, University of Perugia, 06129 Perugia, Italy.

Published: May 2020

The estrogen estradiol is a potent neuroactive steroid that may regulate brain structure and function. Although the effects of estradiol have been historically associated with gonadal secretion, the discovery that this steroid may be synthesized within the brain has expanded this traditional concept. Indeed, it is accepted that de novo synthesized estradiol in the nervous system (nE2) may modulate several aspects of neuronal physiology, including synaptic transmission and plasticity, thereby influencing a variety of behaviors. These modulations may be on a time scale of minutes via non-classical and often membrane-initiated mechanisms or hours and days by classical actions on gene transcription. Besides the high level, recent investigations in the cerebellum indicate that even a low aromatase expression can be related to the fast nE2 effect on brain functioning. These pieces of evidence point to the importance of an on-demand and localized nE2 synthesis to rapidly contribute to regulating the synaptic transmission. This review is geared at exploring a new scenario for the impact of estradiol on brain processes as it emerges from the nE2 action on cerebellar neurotransmission and cerebellum-dependent learning.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247543PMC
http://dx.doi.org/10.3390/ijms21093316DOI Listing

Publication Analysis

Top Keywords

novo synthesized
8
synthesized estradiol
8
synaptic transmission
8
estradiol
5
estradiol role
4
role modulating
4
modulating cerebellar
4
cerebellar function
4
function estrogen
4
estrogen estradiol
4

Similar Publications

mTORC1 regulates the pyrimidine salvage pathway by controlling UCK2 turnover via the CTLH-WDR26 E3 ligase.

Cell Rep

January 2025

Department of Pharmacology, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA; Chemical Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Tri-Institutional PhD Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address:

One critical aspect of cell proliferation is increased nucleotide synthesis, including pyrimidines. Pyrimidines are synthesized through de novo and salvage pathways. Prior studies established that the mammalian target of rapamycin complex 1 (mTORC1) promotes pyrimidine synthesis by activating the de novo pathway for cell proliferation.

View Article and Find Full Text PDF

The aerial epidermis is a major site of quinolizidine alkaloid biosynthesis in narrow-leafed lupin.

New Phytol

January 2025

Section for Plant Biochemistry and Copenhagen Plant Science Centre, Department of Plant and Environmental Sciences, University of Copenhagen, 1871, Frederiksberg, Denmark.

Lupins are promising protein crops that accumulate toxic quinolizidine alkaloids (QAs) in the seeds, complicating their end-use. QAs are synthesized in green organs (leaves, stems, and pods) and a subset of them is transported to the seeds during fruit development. The exact sites of biosynthesis and accumulation remain unknown; however, mesophyll cells have been proposed as sources, and epidermal cells as sinks.

View Article and Find Full Text PDF

generation of dual-target compounds using artificial intelligence.

iScience

January 2025

Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan.

Drugs that interact with multiple therapeutic targets are potential high-value products in polypharmacology-based drug discovery, but the rational design remains a formidable challenge. Here, we present artificial intelligence (AI)-based methods to design the chemical structures of compounds that interact with multiple therapeutic target proteins. The molecular structure generation is performed by a fragment-based approach using a genetic algorithm with chemical substructures and a deep learning approach using reinforcement learning with stochastic policy gradients in the framework of generative adversarial networks.

View Article and Find Full Text PDF

Vitamin D is increasingly recognized for its role in cardiovascular health beyond its well-established effects on bone metabolism. This review synthesizes findings from observational studies, interventional trials, and meta-analyses to clarify the mechanisms through which vitamin D impacts cardiovascular health, including its influence on vascular function, inflammation, and metabolic pathways. Additionally, this review emphasizes the importance of a personalized approach to vitamin D supplementation, integrating individual cardiovascular risk profiles, baseline vitamin D levels, and comorbid conditions, such as hypertension and diabetes.

View Article and Find Full Text PDF

Induction of Erythropoietin by dietary Medium-Chain Triacylglycerol in Humans.

Am J Physiol Endocrinol Metab

January 2025

The August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.

Erythropoietin (EPO) is pivotal in regulating red blood cell (erythrocyte) concentrations and is primarily synthesized in the kidney. Recent research has unveiled a possible link between elevated circulating concentrations of ketone bodies (KB) and circulating EPO concentrations, however, it is not known whether nutritionally induced endogenous ketogenesis can be a stimulus to induce EPO in humans. Therefore, this study aimed to assess whether acute and chronic intake of medium-chain fatty acid (MCFA)-containing triacylglycerol (MCT), which rapidly enhances endogenous circulating KB, would elevate circulating EPO concentrations in humans, as indicated by prior work with exogenous KB administration.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!