Gonadal Steroids And Their Effect On Immune Function.

IN THE NAME OF GOD,

THE COMPANIONATE THE MERCIFUL

Mahmoud Najafi

Gonadal SteroidsAnd Their Effect On

Immune Function

Gonadal Steroids

AndrogensEstrogensProgesterone

Woman have:

A more vigorous immune responseA more developed thymusHigher immunoglobulin concentrationStrong primary and secondary responsesMore resistance to the induction of

toleranceGreater ability to reject tumor and allograft

A higher female/male susceptibility ratio:

Systemic Lupus Erytematosus(10:1)Rheumatoid Arthritis(4:1)Multiple SclerosisMyasthenia GravisAutoimmune 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 40-50 (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

ThymusBone MarrowPeripheral 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 hypothalamusGnRH 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 enhancedLevel of variety of cytokine declineElevated 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