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Researchers at Leipzig University’s Faculty of Medicine and Shandong University in China have discovered a new mechanism that is used by a male sex hormone essential for muscle and bone function. The findings could lead to the development of new drugs with fewer side effects, for use in applications such as strengthening the muscles of immobile patients. The researchers have published their findings in the prestigious journal Cell.
Androgens are hormones that control the development of male sexual characteristics. The most powerful of the androgens is called 5α-dihydrotestosterone (5α-DHT). Among other things, it is essential for bone and muscle function and for the development of secondary male sexual characteristics during puberty. As a driver of bone and muscle formation, 5α-DHT increases bone mineral density and promotes skeletal muscle growth to increase muscle strength.
In this international study, the scientists were able to show that one of the adhesion G protein- coupled receptors – GPR133 – is activated by the androgenic steroid hormone 5α-DHT. “This activation can, among other things, increase the contractile force of skeletal muscles, and our study also uses a newly developed, potent activator of this receptor to specifically trigger this effect,” says Professor Ines Liebscher, Professor of Signal Transduction at Leipzig University and co-leader of the study.
Increasing muscle strength with the chance of significantly fewer negative effects of androgens
Activation of GPR133 by the novel agonist AP503 increases muscle strength without triggering a specific negative effect that is otherwise observed when androgens are administered. For example, increased and prolonged exposure to testosterone can promote the development of prostate cancer, as evidenced by tissue changes in the prostate in mice after only two weeks of androgen administration. This side effect has not yet been observed with AP503.
In addition, the current study uses structural biology methods to elucidate the molecular basis of the interaction between the steroid hormone, the substance AP503 and GPR133. This will allow the activator to be specifically optimised and further developed into a new therapeutic agent. This could lead to the development of new muscle-strengthening drugs with a lower side-effect profile.
This publication is the result of a long-standing and successful collaboration between the Rudolf Schönheimer Institute of Biochemistry and the research group of Professor Jin-Peng Sun at Shandong University in China. The researchers are currently working on several follow-up studies to further investigate the use of AP503 in disease processes and the role of GPR133 in the organism. Here the data were analysed in animal models. Further studies are needed to investigate the applicability of the findings to humans.
More information: Research into signalling molecules such as adhesion G protein-coupled receptors has been a focus at Leipzig University for more than a decade. Scientists have made important discoveries about the activation, signalling and physiological functions of these receptors. The German Research Foundation (DFG)-funded Collaborative Research Centre 1423, “Structural Dynamics of GPCR Activation and Signaling”, is currently working intensively in this area.
Translation: Matthew Rockey
Professor Ines Liebscher
Rudolf-Schönheimer Institute of Biochemistry
Faculty of Medicine, Leipzig University
Email: Ines.liebscher@medizin.uni-leipzig.de
Tel.: +49341/97-22141
Original publication in Cell: Identification, structure, and agonist design of an androgen membrane receptor. https://doi.org/10.1016/j.cell.2025.01.006
In this international study, the scientists were able to show that one of the adhesion G protein- co ...
Created in BioRender. Liebscher, I. (2025)
Prof Torsten Schöneberg (2nd from left) and Prof Ines Liebscher (3rd from right) at a meeting in Lei ...
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