GRAVES AUTOIMMUNE SERUM INHIBITS GONADAL STEROIDOGENESIS - DEVELOPMENT OF A LEYDIG-CELL BIOASSAY TO IDENTIFY BROAD-SPECTRUM ANTI-ENDOCRINE AUTOANTIBODIES
Kp. Willey et al., GRAVES AUTOIMMUNE SERUM INHIBITS GONADAL STEROIDOGENESIS - DEVELOPMENT OF A LEYDIG-CELL BIOASSAY TO IDENTIFY BROAD-SPECTRUM ANTI-ENDOCRINE AUTOANTIBODIES, Journal of reproductive immunology, 24(1), 1993, pp. 45-63
In order to establish an assay for the detection of autoimmune sera wi
th broad spectrum activity, we have investigated the effect of unselec
ted normal and Graves' disease sera upon steroidogenesis by gonadal ce
lls. Steroidogenesis was enhanced by the addition of normal serum in a
3-h primary Leydig cell bioassay, but was inhibited by the majority o
f Graves' sera. The inhibition was not related to clinical thyroid par
ameters, such as the severity of the TSH-binding inhibition index, and
was not overcome by other agonists or second messenger supplements. A
lthough pituitary TSH preparations bound to and stimulated Leydig cell
s, TSH receptor mRNA was not detectable and pure recombinant TSH faile
d to bind or stimulate, indicating contamination of pituitary TSH with
LH. The binding of hCG to the Leydig cell luteinizing hormone recepto
r was not perturbed by the Graves' autoimmune sera, indicating that cr
oss-reactive anti-TSH receptor antibodies were not responsible for the
inhibition. By use of intermediates in the stimulatory pathway, the s
ite of Graves' serum inhibition was identified to be distal to hormone
receptor/adenylate cyclase coupled responses and proximal to supply o
f cholesterol for steroidogenesis.