Characteristics of antibody produced during chronic treatment with LHRH

In a patient with hypogonadotropic hypogonadism treated with luteinizing hormone releasing hormone (LHRH), secondary failure of both subjective and hormone responses occurred at the time of appearance of binding of ¹²⁵I LHRH by the patient's serum. On electrophoresis of the patient's serum with ¹²⁵I LHRH, label was found only in the gamma globulin region. ¹²⁵I LHRH added to the patient's serum was precipitated by sheep antihuman immunoglobulin G (anti IgG) but not by sheep anti human immunoglobulin M (anti IgM). Competitive displacement of ¹²⁵I LHRH by unlabeled LHRH was demonstrated while TSH releasing hormone (TRH), somatostatin and rat pituitary hormones showed no displacement when tested at concentrations 5 x 10⁶ greater than that of LHRH. Studies using 14 different analogs of LHRH revealed that those with changes at the carboxy terminus showed binding similar to LHRH. It is concluded that IgG antibody to LHRH was produced in this patient by repeated administration of synthetic LHRH. It is further concluded that antibody specificity is directed toward the N terminus region.