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Mechanism of Dopaminergic Suppression of Gonadotropin Secretion in Men*

1980; Oxford University Press; Volume: 51; Issue: 2 Linguagem: Inglês

10.1210/jcem-51-2-209

1945-7197

Carol A. Huseman, Jane A. Kugler, IDA G. SCHNEIDER,

Estrogen and related hormone effects

Dopamine (DA) has been shown by previous investigators to inhibit gonadotropin secretion in man. The purpose of our study was to determine the mechanism (s) by which this inhibition occurs. DA, its antagonist haloperidol (HA), and gonadotropin-releasing hormone (GnRH) were used as investigative agents. Conclusions are based on changes in LH pulse frequency and amplitude, as well as mean gonadotropin response and response areas during various treatments. Five normal men (23–30 yr of age) received 4-h constant iv infusions of saline (0), DA (4 µg/kg/min), synthetic GnRH (0.4 µg/min), DA (4 µg/tg/kg/min) plus GnRH (0.4 µg/min), and HA (2.5 mg, orally). Blood was sampled via an indwelling cannula from the opposite arm every 15 min for 1 h before, during, and after the infusion or HA treatment. The LH and FSH concentrations were measured in each sample by RIA. Testosterone was also measured but only in samples at hourly intervals. The maximum LH concentrations during the 0, DA, GnRH, DA plus GnRH, and HA treatments were 11.9 ± 2.4, 6.9 ± 1.5, 52.0 ± 3.8, 37.8 ± 5.5, and 14.1 ± 0.2 (±SE) mlU/ml, respectively. The inhibitory effect of DA on LH secretion occurred by a suppression of serum LH pulse frequency [one LH pulse per 128 min (O) us. one episode per 300 min (DA)] and also by suppression of the LH pulse amplitude [4.7 ± 0.6 (O) us. 2.2 ± 0.2 (SE) mlU/ml (DA)]. A highly significant increase in LH response occurred in all subjects during the constant GnRH infusion. The addition of DA to the infusate significantly suppressed this LH response to GnRH. HA administration slightly increased the LH pulse amplitude [6.3 ± 0.9 (SE) mlU/ml] compared with saline infusion [4.7 ± 0.6 (SE) mlU/ml]. The effect of DA on serum FSH was variable. A significant FSH response to GnRH occurred in all subjects. This FSH response to GnRH was blunted by DA in three of the five subjects. HA had no effect on FSH secretion. Serum testosterone concentrations showed no significant change under any treatment. These observations demonstrate that DA-induced inhibition of LH secretion in men is associated with a reduction in both pulse frequency and amplitude of LH secretion. Further, the observation that partial inhibition of LH secretion occurred even in the presence of constant GnRH and DA infusion suggests that DA may also modulate the gonadotrope response to GnRH.