THE BIO/IMMUNO RATIO OF SERUM LUTEINIZING-HORMONE INCREASES AFTER ORCHIECTOMY IN PROSTATIC-CANCER PATIENTS AND IS ASSOCIATED WITH DECREASED MOLECULAR-WEIGHT AND APPEARANCE OF ISOHORMONES WITH ALKALINE PL VALUES

Serum concentrations of bioactive (B) and immunoreactive (I) luteinzing hormone (LH) were determined in six patients with prostatic cancer before castration and at frequent intervals after the operation up to 6 mo. B-LH increased in 6 mo from 11 ± 1 to 90 ± 9 (mean ± SEM, n = 6) IU/liter (p < 0.01), and I-LH from 9 ± 1 to 37 ± 5 IU/liter (p < 0.01). Accordingly, a significant increase in the B/I ratio of LH occurred at the same time, from 1.3 ± 0.1 to 2.4 ± 0.2 (p < 0.01). To elucidate the molecular basis of the B/I ratio change, serum samples obtained before and 2-6 mo after orchiectomy were fractionated by gel filtration and chromatofocusing, and the eluted fractions were analyzed for B-LH and I-LH. In gel filtration, the fractions with the highest B-LH and I-LH contents were eluted later in the post-castration samples than in the pretreatment samples (mean V(e)/V(o) 1.31 - 1.32 vs. 1.26 - 1.28; p < 0.02 - 0.01), indicating a small reduction in the average M(r) of the circulating LH after castration. In chromatofocusing, a single major peak of immunoreactivity with a pI value of 7.4 was identified before castration, but in post-castration samples, a significantly large proportion of the immunoreactivity was eluted in the alkaline pI range 7.4 - 9 (22.2 ± 2.4% before, 56.5 ± 5.2% after castration, p < 0.05). These findings indicate that after castration, the increased B/I ratio of serum LH is explained by a preferential increase in isohormones with slightly reduced molecular weights and alkaline pI values.