Tissue expression of steroid hormone receptors is associated with differential immune responsiveness

Abstract

Glucocorticoids and other steroid hormones have been used as treatments against a number of diseases, especially inflammatory conditions in which the immune system is overactive. These treatments have varying degrees of responsiveness among individuals and in different tissues (including brain); therefore, it is important to determine what could account for these differences. In this study, we evaluated expression of steroid hormone receptors in immune cells from lymphoid and non-lymphoid tissues as a possible explanation for tissue-specific differences. We analyzed leukocytes (CD45 + ) in kidney, liver, spleen, and thymus tissues from healthy mice for expression of the receptor for stress hormone (glucocorticoid -GR) as well as other steroid hormones (androgen -AR, progesterone -PR) and found that all tissues expressed these steroid hormone receptors but with varying expression patterns. To determine whether tissue-specific differences were related to immune cell composition, we examined steroid hormone receptor expression in T lymphocytes from each of these tissues and found similar patterns of expression in these cells regardless of tissue source. Because glucocorticoids can also impact brain function, we further examined expression of the stress hormone receptor in brain tissue and found GR expressed in immune cells at this site. In order to investigate the potential impact in an area of neuropathology, we utilized a mouse model of West Nile Virus (WNV). We observed pathological changes in brains of WNV-infected animals and T lymphocytes in the areas of inflammation; however, these cells did not express GR. These data indicate that tissue-specific differences in steroid hormone receptor expression by immune cells could determine responsiveness with steroid hormone treatment.

Physiological interactions between the hypothalamic-pituitary-gonadal axis and spleen in rams actively immunized against GnRH

“…Among them, sex steroids have been intensively investigated and established to play a significant role in the regulation of immune function based on the following facts: i) the immune responses and circulating immune cytokine profiles are altered by gonadectomy and sex steroid hormone replacement [2][3][4]; ii) Sex steroid receptors, including both androgen and estrogen receptors were observed to be expressed in spleen, thymus and peripheral immune cells [5][6][7], supporting the roles of sex steroids in immune system development and modulation; iii) sexual dimorphic immune responses are well established in vertebrates. Females generally exhibit more-robust antibody and cell-mediated immune responses to antigens and, are more likely than male individuals to produce autoreactive antibodies of pathogenic potential [8,9].…”

Sex Steroids Modulate Fish Immune Response

“…These are differentially expressed in tissues and show high affinity for both testosterone and 11 -hidroxytestosterone (review in Rempel & Schlenk, 2008). However, little is known about the expression of these AR in fish immune tissues, although in mammalian models AR are present in liver, spleen and thymus (Butts et al, 2011).…”

Variability in Laboratory Immune Parameters Is Associated with Stress Hormone Receptor Polymorphisms

“…Additionally, the normal immune system responds to potentially pathogenic agents by producing effector cytokines, the specific type, level, and duration of which depend upon the amount and nature of the inciting pathogen as well as the intrinsic capabilities of the individual. Most immune effector (Th1 and Th2) and regulatory (T reg , Tr1, and Th3) cells express glucocorticoid receptors (GR) and β 2 -adrenergic receptors (β2AR) [2,3], which will bind corticosteroids and catecholamines, respectively. Every healthy individual produces varying basal amounts of these hormones throughout the day which results in differing impacts on immune cell numbers and functions.…”