Do alpha-adrenergic mechanisms regulate spontaneous or opiate-modulated pulsatile luteinizing hormone secretion in man?

Brain noradrenergic mechanisms participate in the excitatory control of episodic LH release in many experimental animals, including the nonhuman primate. In addition, augmentation of pulsatile LH release in the rodent in response to opiate receptor antagonists is dependent upon intact central noradrenergic pathways. The applicability of these tenets to humans is not known. We tested the excitatory influence of brain noradrenergic systems on pulsatile LH secretion in normal men by administering phenoxybenzamine (an irreversible, preferentially postsynaptic, alpha 1-receptor blocker) or alpha-methyldopa (an inhibitor of brain adrenergic transmission). Five normal men underwent repetitive (every 20 min) venous sampling for 8 h to characterize episodic LH release quantitatively under basal conditions and after the administration of naltrexone, a potent opiate receptor antagonist which stimulates puslatile LH release. Subjects received saline, phenoxybenzamine (1 mg/kg, iv, over 90 min), or alpha-methyldopa (250 mg, orally, every 6 h). The following parameters of spontaneous episodic LH secretion were not altered after phenoxybenzamine or alpha-methyldopa administration: mean and integrated serum LH concentrations, LH pulse frequency, LH pulse amplitude (percentage or milliinternational units per ml increment), and absolute peak serum LH values. In addition, the administration of adrenergic inhibitors did not impede the capacity of naltrexone to significantly augment pulsatile LH secretion in these subjects. We conclude that in the doses used, phenoxybenzamine and alpha-methyldopa do not alter spontaneous or opiate-modulated episodic LH release in normal men.