Modulation of pulsatile gonadotropin secretion by testosterone in man

Area of Science:

• Endocrinology
• Reproductive Medicine
• Neuroendocrinology

Background:

• Primary testicular deficiency in animals increases luteinizing hormone (LH) pulse frequency.
• Pulsatile secretion patterns of follicle-stimulating hormone (FSH) are not well understood.
• The role of testosterone (T) in regulating gonadotropin pulsatility in humans requires elucidation.

Purpose of the Study:

• To investigate the effect of testosterone (T) on the pulsatile secretion of LH and FSH in men.
• To compare gonadotropin secretion patterns in normal men, hypogonadal men, and hypogonadal men undergoing T replacement therapy.

Main Methods:

• Frequent blood sampling (every 10 minutes for 12 hours) was performed in six normal men and six primary hypogonadal men.
• Hypogonadal men were studied before and after T replacement therapy (T enanthate, 200 mg, im, every 2 weeks).
• Episodic secretion patterns of LH and FSH were analyzed for pulse frequency and amplitude.

Main Results:

• Primary hypogonadal men exhibited significantly lower T levels and higher LH pulse frequency and amplitude compared to normal men.
• Testosterone replacement therapy in hypogonadal men led to increased T levels and significantly decreased LH pulse frequency and amplitude.
• FSH secretion patterns paralleled LH secretion, showing decreased pulse frequency and amplitude with T replacement.

Conclusions:

• Diminished T negative feedback in hypogonadism results in high-frequency, high-amplitude LH and FSH pulses.
• Testosterone replacement therapy effectively reduces LH and FSH pulse frequency and amplitude in hypogonadal men.
• These findings suggest that testosterone or its metabolites act on the central nervous system to modulate the hypothalamic LHRH pulse generator.