Hormones Action on Erythrocytes and Signaling Pathways

*Camila Cristina Guimarães-Nobre, Evelyn Mendonça-Reis, Lyzes Rosa Teixeira-Alves and Clemilson Berto Junior*

### **Abstract**

Erythrocytes are the most abundant cell type in the human body, although considered as merely hemoglobin carriers for a long time. Extensive studies on its biochemical pathways, metabolism, and structure-activity relationship with a consistent number of publications demonstrated the presence of autocrine, paracrine, and endocrine hormone receptors. In this chapter, some of these hormones will be discussed, bringing attention to those that regulate erythrocyte survival, disease connection, and functionality.

**Keywords:** hormones, signaling pathway, TSH, endothelim-1, angiotensin II

### **1. Introduction**

In the human body, there are several hormones that regulate different functions, such as growth and development, metabolism, electrolyte balance, and reproduction [1]. These functions have already been widely studied, and most of them are very well elucidated; even so, there are still aspects that have not yet been well explored. For example, the relationship between erythrocytes and hormones. Erythrocytes were treated as merely hemoglobin carriers for a long time, with small or none of the complex functions as seen currently.

It has already been seen that in healthy erythrocytes, adenosine can increase 2,3-bisphosphoglycerate (2,3-BPG) through activation of the ADORA2B receptor (A2B), suggesting that increasing adenosine levels increases oxygen release, which is positive for preventing tissue damage from acute ischemia. However, in sickly erythrocytes, the increase in oxygen release through the induction of 2,3-BPG by adenosine can be harmful, as oxygen release of oxygen induces the sickling of these erythrocytes [2].

In 1999, a study by Tuvia et al. showed that exposure of erythrocytes to adrenaline led to a concentration-dependent increase in erythrocyte deformability, and consequently, increased oxygen delivery to tissues [3]. Another study reported that adrenaline and epinephrine dose-dependently increase the rate of erythrocyte agglutination through alpha-1 adrenergic receptor activation. Furthermore, this study suggested that the effect of adrenaline was caused by an increase in Ca2+ entry into the erythrocyte, with consequent activation of the erythrocyte calmodulin, cyclooxygenase,

and phospholipase A2 and leading to the release of K+ from erythrocytes through Ca2+-dependent K+ channels, which is considered a manifestation of eryptosis. In summary, the potentiation of α1AR activation increases, while β2AR decreases the rate of eryptosis [4].

These studies present modulation of erythrocyte function by surface receptors and some of the signaling pathways that might be triggered inside the cell. In this chapter, the focus is to explore the actions of three well-studied hormones on erythrocyte function and some reports regarding intracellular pathways involved in these modulations.
