Melatonin and Androgen Receptor Expression Interplay Modulates Cell-Mediated Immunity in Tropical Rodent Funambulus pennanti: An In-Vivo and In-Vitro Study

Abstract

An inverse relation exists between melatonin and androgen in most of the seasonally breeding rodents, but the regulation of their receptors in modulation of immune function has never been reported. The present study accessed the expression pattern of melatonin receptor types (mt1R & mt2R), immune parameters (lymphoid organs weight, leucocyte count, delayed type hypersensitivity and lymphocyte proliferation) in spleen and thymus whereas androgen receptor (AR) expression in thymus of Funambulus pennanti during reproductively active phase. In‐vivo melatonin treatment (Mel) and castration (Cx) significantly increased mt1R expression, immune parameters in spleen and thymus but decreased AR expression in thymus only when compared with sham control (Con) squirrels as AR expression was not observed in spleen. Mel alone or in combination with testosterone (T) to Cx squirrels significantly increased mt1R expression, immune parameters in spleen and thymus but decreased AR expression in thymus. T alone in Cx squirrels significantly decreased mt1R expression, immune parameters in spleen and thymus but increased thymic AR expression significantly. In‐vitro thymocyte culture supported our in‐vivo findings. Mel significantly increased mt1R expression, lymphocyte proliferation, IL‐2 secretion but decreased AR expression. T alone significantly decreased aforementioned three parameters but increased AR expression. Combined treatment of Mel and T bring back all parameters to control level. Though we found high mt2R expression, but no significant change has been observed. Thus, present study suggests a clear‐cut trade‐off relation between mt1R and AR expression that might be acting as an important mediator in seasonal adjustment of immune function in tropical rodents.

Melatonin Membrane Receptor Type MT1 Modulates Cell-Mediated Immunity in the Seasonally Breeding Tropical Rodent <i>Funambulus pennanti</i>

“…Sandwich ELISA was performed to quantify the level of IL-2 in culture supernatants according to the manufacturer's instructions (Immunotech, France). The details of the methodology have already been published elsewhere [19] .…”

“…Cell-Mediated Immunity Cell-mediated immune function was assessed by measuring splenocyte proliferation in response to the T cell mitogen concanavalin A (Con-A) using a colorimetric assay based on the reduction of the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) [18] which has been reported and published by our group elsewhere [19] . The spleens of squirrels from all groups were removed under sterile conditions, and splenocytes were isolated from the tissue by compressing the whole spleen between sterile frosted glass slides; separated cells were suspended in ice-cold culture medium [RPMI-1640 plus HEPES supplemented with 1% penicillin (5,000 U/ml) streptomycin (100 g/ml), 1% L -glutamine (2 m M ), 0.1% 2-mercaptoethanol (5 !…”

“…Mean OD values for each set of duplicates were used in subsequent statisti-cal analyses. Response was calculated as the percentage stimulation index, representing the ratio of absorbance of mitogen-stimulated cultures to that of control cultures [19] . The other details of the methodology in F. pennanti were published previously by our group [19] .…”

Enhanced Proinflammatory Cytokine Response to Bacterial Lipopolysaccharide in the Adult Male Rat after either Neonatal or Prepubertal Ablation of Biological Testosterone Activity

“…Besides data on the immunological sexual dimorphism developed in mammals and the precise role played by sex steroid hormones [13] , recent data indicate that endogenous androgen deprivation in men with prostatic cancer did result in reactivation of the immune system function [42] . Another study [43] demonstrated that ODX in rodents, a condition characterized by the absence of any residual adrenal-derived dihydrotestosterone activity [44] , reduced the abundance of ARs in the thymus gland. Moreover, Ahmad and Haldar [43] found that ODX enhanced in vitro thymocyte proliferation and IL-6 secretion, and that these effects of ODX were partly/fully reversed by testosterone replacement treatment.…”

“…Another study [43] demonstrated that ODX in rodents, a condition characterized by the absence of any residual adrenal-derived dihydrotestosterone activity [44] , reduced the abundance of ARs in the thymus gland. Moreover, Ahmad and Haldar [43] found that ODX enhanced in vitro thymocyte proliferation and IL-6 secretion, and that these effects of ODX were partly/fully reversed by testosterone replacement treatment.…”