Modulation of pulsatile gonadotropin secretion by testosterone in man

Abstract

In experimental animals, primary testicular deficiency leads to increased LH pulse frequency. Pulsatile FSH secretion has not been well characterized in any species. To determine the effect of testosterone (T) on the pattern of pulsatile gonadotropin secretion in man, we performed frequent blood-sampling studies in six normal men and six men with primary hypogonadism. All primary hypogonadal men were studied 6-8 weeks after stopping T replacement therapy. Five of the six hypogonadal men were restudied 6-8 weeks after treatment with T enanthate (200 mg, im, every 2 weeks; sampling in this group was 2 weeks after their last T injection). Blood sampling was done at 10-min intervals for 12 h in all subjects, and the pattern of episodic LH and FSH secretion was determined. Normal men had a serum T level of 6.3 +/- 0.3 ng/ml (mean +/- SEM), a LH level of 34 +/- 3 ng/ml, and a LH pulse pattern characterized by low frequency (7.6 +/- 0.7 pulses/12 h) and low amplitude (16 +/- 1 ng/ml). Compared to normal men, primary hypogonadal men had a significantly lower T level (2.9 +/- 0.4 ng/ml) and significantly higher LH pulse frequency (13.0 +/- 1.3 pulses/12 h), amplitude (51 +/- 7 ng/ml), and mean level (222 +/- 26 ng/ml). Reinstitution of T replacement therapy in hypogonadal men resulted in a significant increase in the T level (4.7 +/- 0.5 ng/ml) and significant decreases in LH pulse frequency (7.2 +/- 1.6 pulses/12 h) and amplitude (41 +/- 5 ng/ml) as well as mean LH level (75 +/- 15 ng/ml). FSH levels fluctuated in a distinctly pulsatile pattern in all three groups. Differences in pulsatile FSH secretion between primary hypogonadal men before and during T therapy and normal men paralleled those in pulsatile LH secretion in both frequency and amplitude. These results demonstrate that in man 1) diminished T negative feedback results in high frequency (circhoral), high amplitude LH and FSH pulses; 2) T replacement decreased LH and FSH pulse frequency and amplitude as well as mean levels; and 3) the decreased LH and FSH pulse frequency with T treatment implies that T or a metabolite of T acts on the central nervous system to slow the hypothalamic LHRH pulse generator.