[Unfavourable cardiovascular consequences of adult growth hormone deficiency]. / A felnottkori növekedésihormon-hiány szív- és érrendszeri szövodményei.

The growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis plays a crucial role in maintaining the normal function of the cardiovascular system. Results of the last decades demonstrated that GH-IGF-1 takes part in regulating peripheral resistance and contributes to preserving physiological cardiac mass and left ventricular function. Vasculoprotective functions of the GH-IGF-1 axis are believed to counteract atherosclerosis. Unlike in childhood, when GH-deficiency results in growth retardation, GH deficiency does not cause specific symptoms in adults. Adult growth hormone deficiency (AGHD) is characterized by a clustering of cardiometabolic risk factors resulting in a clinical picture similar to the metabolic syndrome. Besides visceral obesity, dyslipidemia and insulin resistance, novel cardiovascular risk factors, such as chronic low-grade inflammation, oxidative stress and prothrombotic state have also been reported in AGHD and may contribute to the increased cardiometabolic risk. Based on a growing body of evidence, long-term GH-replacement improves lipid profile significantly and has a favorable impact on body composition, endothelial function, left ventricular mass as well as the novel, non-traditional cardiometabolic risk factors. Increased mortality associated with the disease is now considered to be multicausal and as such cannot be solely attributed to the GH-deficiency. The etiology of GH-deficiency, treatment of the underlying pathology as well as the inadequate treatment of coexisting hormonal deficiencies might also be responsible for the increased mortality. Nevertheless, in hypopituitarism, adequate replacement therapy including GH-substitution may result in a mortality that is comparable to the general population. Orv Hetil. 2023; 164(41): 1616-1627.

Membrane Potential Distinctly Modulates Mobility and Signaling of IL-2 and IL-15 Receptors in T Cells.

The high electric field across the plasma membrane might influence the conformation and behavior of transmembrane proteins that have uneven charge distributions in or near their transmembrane regions. Membrane depolarization of T cells occurs in the tumor microenvironment and in inflamed tissues because of K+ release from necrotic cells and hypoxia affecting the expression of K+ channels. However, little attention has been given to the effect of membrane potential (MP) changes on membrane receptor function. Therefore, we studied the influence of membrane de- and hyperpolarization on the biophysical properties and signaling of interleukin-2 (IL-2) and interleukin-15 (IL-15) receptors, which play important roles in T cell function. We investigated the mobility, clustering, and signaling of these receptors and major histocompatibility complex (MHC) I/II glycoproteins forming coclusters in lipid rafts of T cells. Depolarization by high K+ buffer or K+ channel blockers resulted in a decrease in the mobility of IL-2Rα and MHC glycoproteins, as shown by fluorescence correlation spectroscopy, whereas hyperpolarization by the K+ ionophore valinomycin increased their mobility. Contrary to this, the mobility of IL-15Rα decreased upon both de- and hyperpolarization. These changes in protein mobility are not due to an alteration of membrane fluidity, as evidenced by fluorescence anisotropy measurements. Förster resonance energy transfer measurements showed that most homo- or heteroassociations of IL-2R, IL-15R, and MHC I did not change considerably, either. MP changes modulated signaling by the two cytokines in distinct ways: depolarization caused a significant increase in the IL-2-induced phosphorylation of signal transducer and activator of transcription 5, whereas hyperpolarization evoked a decrease only in the IL-15-induced signal. Our data imply that the MP may be an important modulator of interleukin receptor signaling and dynamics. Enhanced IL-2 signaling in depolarized Treg cells highly expressing IL-2R may contribute to suppression of antitumor immune surveillance.