Gonadal Steroids And Their Effect On Immune Function

Gonadal Steroids  Androgens  Estrogens  Progesterone

Woman have:  A more vigorous immune response  A more developed thymus  Higher immunoglobulin concentration  Strong primary and secondary responses  More resistance to the induction of tolerance  Greater ability to reject tumor and allograft

A higher female/male susceptibility ratio:  Systemic Lupus Erytematosus(10:1)  Rheumatoid Arthritis(4:1)  Multiple Sclerosis  Myasthenia Gravis  Autoimmune thyroid disease

Gonadal steroids and SLE  Decreased androgen/estrogen ratio (aggravated) –An increase aromatase activity –Pregnancy –Administration of estrogens containing contraceptives  Increased androgen/estrogen ratio (ameliorated) –A therapeutic effect  Is aggravated by estrogens

Gonadal steroids and RA  Oral contraceptive and Pregnancy –Mitigate the development of the disease  The age of onset of RA in woman is (Menopause)  Is ameliorated by estrogens

Animal Models  Female animal –More rapidly reject allograft transplanted –More vigorous immune response Humoral immunity Cell mediated immunity

Female Rats  Administration of testosterone –Largely prevents the onset of autoimmune disease –Castrated male demonstrate disease acceleration  Thymectomy –Ablates beneficial effect of testosterone

Androgen and Estrogen binding site  Thymus  Bone Marrow  Peripheral immune system  Gonadectomy –Hyperplasia of the thymus  The administration of exogenous androgen and estrogen –Thymic involution

Progenitor T & B lymphocytes  Sex steroids have receptor –Positive effect on T-cell lymphopoiesis –Negative effect on B-cell lymphopoiesis Ovarietomy  Increase number of B-cell  T & B lymphopoiesis is suppressed during pregnancy

Influencing the function of mature T and B cells  Estrogen  Increase activity of CD4+ T cells  Decrease activity of CD8+ T cells  enhances IFN-γ (In vitro study)  Treatment by estrogen Increase the number of autoreactive immunoglobulin  Androgen  Have receptor on peripheral T and B cells

GnRH  Synthesis within the hypothalamus  GnRH RNA has been detected in spleen & thymus  T-cell has GnRH receptor –May be involved in the maturation and senescence cells within the immune system

Pregnancy  Measure of cell-mediated immunity are suppressed  Humoral immunity is preserved or enhanced  Level of variety of cytokine decline  Elevated level of Glucorticoids –Potent inhibitory of IFN-γ Is a powerful abortifacient

Hypersensitivity and Pregnancy  Systemic Lupus Erytematosus –Type III Hypersensitivity –aggravated during the pregnancy  Rheumatoid Arthritis –Type IV Hypersensitivity –suppressed during the pregnancy

Hypersensitivity and Pregnancy  MS −Progesterone  Attenuate disease severity Reduce the inflammatory response Reduce demyelination in the spinal cord

Bone metabolism  Estrogens & androgens –Bone protective effect –Decreased of inflammatory cytokines TNF IL-1, IL-6  Bone loss in post-menopausal –Estrogen replacement therapy

Androgens  Anti-inflammatory  Receptors present on immune tissues  Immunosuppressive on both T & B cells  Decrease thymic mass  Suppress antibody response  Increase TGF-β

Estrogens  Pro or Anti-inflammatory (dependent on the disease)  Receptors present on immune tissues  Decrease thymic mass  Inhibit suppressive T-cells  Facilitate T-helper lymphocyte maturation  Stimulate B-cell mediated antibody response

Progesterone  Anti-inflammatory  Receptors present on some immune tissues