Hypogonadism in a Male with an Immunologically Active, Biologically Inactive Luteinizing Hormone: Characterization of the Abnormal Hormone*

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Abstract
Studies were performed to characterize the LH of a male with hypogonadism attributable to an immunologically active, biologically inactive LH. We wished to determine 1) the biologicalactivity of the LH in in vitro systems and 2) the chromatographic characteristics of LH, FSH, and their subunits in the patient's serum and urine. Before therapy the patient's serum LH was 8.0 ± 0.5 mIU/ml (LER 907), which is significantly higher than in normal men (1.3 ±0.5 mlU±ml; mean ± SD). The response to an LRH infusion was enhanced and biphasic. During the infusion (0.2 µg/min for 4 h) a 3-fold rise occurred at 75 min, and a second rise occurred at 180 min. Basal serumFSH, α-subunit, and LH β-subunit concentrations were also elevated and exhibited an exaggerated rise during the LRH infusion. The in vitro bioactivity of LH in serum and urine, as measured in dispersed rat interstitial cells by means of testosterone (T) and cAMP production, was low in comparison with values found in normal men. There was no significant increase in bioactive LH concentrations during LRH stimulation. The patient was treated with T (300 mg im every 2 weeks for 9 weeks)and the studies wererepeated. The baseline concentration of LH was suppressed to 0.3±0.1 mIU/ml. During stimulation with LRH the early rise did not occur; the late rise (to 21.2 mIU/ml) was observed at 240 min as before. The basal level of FSH and the subunits was likewise suppressed as was the first phase of the response to the LRH infusion. The bioactive LH concentration was higher than in theuntreated state, as measured by both T production (in response to serum and urine) and cAMP production (in response to serum). Furthermore in response to the rise in endogenous LH observed during LRH stimulation the serum T concentration increased from 787 to 1095 ng/dl and the serum estradiol concentration rose from 56 to 161 pg/ml. Chromatography on Sephadex G-100 revealed immunoreactive LH FSH and subunit peaks eluting in the same areas as authentic standards. Larger or smaller molecular weigh moieties were not present. These studies demonstrate that 1) the patient's hypogonadism is attributable to the presence of an immunologically active, biologically inactive LH molecule in the circulation as well asthe urine; 2) the biological activity of the abnormal LH increases in response to T therapy;3) theimmunologically measurable LH has a molecular weight comparable to that of authentic LH and is notdetectable as a larger (precursor) or smaller (fragment) immunoreactive molecule on Sephadex chromatography; and 4) subunits are not present in excessive quantities. These findings suggest that the biological inactivity of the patient,s LH molecule is not attributable to a defect in activationof an inactive precursor of high molecular weight to an active form. The nature of th abnormality is not yet known. (J Clin Endocrinol Metab52: 1143, 1981)

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