Investigation Of Androgen Recetor Gene Expression In Systemic Lupus Erythematosus Patients

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease of unknown cause that produces lesions of multiple organs. It occurs more frequently in woman, the male-female ratio is 8 to 13:1. It has been noted that androgen play a role in the development of SLE. A lupus-like disease of New Zealand mice is ameliorated by oophorectomy or treatment with male hormones. SLE is much more common among women in their childbearing years. In addition, SLE has been observed in some males with Klinefelter's syndrome. Lubahn et al have found that androgen is lower in plasma of SLE patient than that of the control. The gene expression of androgen receptor (AR) has not been reported, so we examined mRNA expression of AR in peripheral leikocytes. The venous blood was obtained from healthy men and women, the leukocytes were isolated by Tian-Ying method; total RNA was isolated by single step method of acid guanidinium-thiocyanate-phenol-chlofonn. 572 bp ARcDNA probe was labeled by a-32P-dAIP using random hexadeoxyribonucleotides to primer DNA synthesis from any linear double-strand DNA template. The labeled, denatured DNA probe was hybridized to the RNA transferred on the nylon membrane. Autoradiogram of Northern blot revealed that a 9.4 kb band in all samples, which is consistent with AR mRNA in human prostate reported by Lubahn et al, demonstrating AR mRNA expression in human peripheral leukocytes and the role of androgen on leukocyte's function. The specificity of Northern blot is high, converse is the sensitivity. To detect AR gene expression, 25ug total RNA or so (corresponding with 20m1 venous blood) may be used at least. By RT-PCR we investigated AR RNA expression , only 6 to 10 ml blood was used and the sensitivity is high. To determine the difference of AR in peripheral leukocytes among SLE patients and the healthy controls, 8 active female SLE patients were choosed , they were diagnosed with the criteria for classification of systemic lupus erythematosus of ARA in 1982 and have not taken any glucocortcoid drugs. 10 healthy women were selected as the control group. An ARcDNA fragment of the expected size of 390 bp was detected in SLE patient white cell as well as in the normal control. With the linear relationship between the quantity of mRNA and the final PCR product, we found that AR expression in SLE patient was much more than that in the normal control. For venous blood can be easily obtained, it is conventional to investigate the role of andogen and androgen receptor in pathological stages with the method shown in this paper. On the other hand, it is helpfiil to study the other steroid receptors. The over-expression of AR in SLE leukocytes may be the result of AR to the lower androgen level in plasma. For the androgen deficiency in SLE, Strand suggested that mild androgen dehydroepiandrosterone may be useful in the treatment of SLE. Long-term GC administration may result in some deleterious side-effects, such as muscular weakness,atophy and necrosis, diabetes, fattiness, osteopenia, osteoporosis andavascular necrosis and susceptibility to infections. On the other hand,administraion of glucocortcoids inhibits ACTH secretion, involutes theadrenal cortex and results in further androgen deficiency. Androgenreplacement therapy may reduce damage caused by glucocortcoidsadIninistraion. This replacement has shown some beneficial clinicaladvance and needs more suPportive datas. Some auhors suggested that.immune abnormalities is as...