Testosterone reduces the bioactivity of luteinizing hormone (LH) in man

The effect of testosterone on LH bioactivity was investigated in six adult men (aged 40-56 years) with primary hypogonadism. Two men received a 400 mg testosterone implant, another two 800 mg, and the final two patients received both doses in consecutive courses separated by at least 4 weeks. Plasma samples, obtained before and at 1, 2, 4, 8, 16 and 24 weeks after treatment, were analysed for bioactive LH by the mouse Leydig cell bioassay, and immunoreactive LH and testosterone (T) by standard radioimmunoassays. The bioactive to immunoreactive (B:I) LH ratio, an index of LH biopotency, was calculated and the results compared with those from a group (n = 17) of healthy adult men. Before treatment, both bioactive and immunoreactive LH levels in the patients were higher and T levels lower than in the normal men (P less than 0.001). The mean +/- SD B:I LH ratio (3.5 +/- 0.6) in the patients was greater (P less than 0.05) than in the controls (2.7 +/- 0.7), indicating that in primary testicular failure, increased amounts of LH with enhanced bioactivity are secreted. Following T administration, a dose-related increase in circulating T and a reciprocal decrease in LH levels was observed between 1 and 16 weeks of treatment. However, there was a more pronounced decline in bioactive rather than immunoreactive LH levels, so that the B:I LH ratios decreased (P less than 0.001) from basal values after treatment. There was a negative correlation (r = -0.82, P less than 0.001) between circulating T levels and B:I LH ratios; the stronger the feedback signal, the lower the B:I LH ratio. It is concluded that testosterone negative feedback modifies not only the quantity but also the biological quality of secreted LH.