Jarjour L T, Handelsman D J, Raum W J, Swerdloff R S
Endocrinology. 1986 Oct;119(4):1726-32. doi: 10.1210/endo-119-4-1726.
Controversy exists on whether dopamine (DA) stimulates or inhibits GnRH secretion and whether its effects are mediated via alpha-adrenergic receptors or dopaminergic receptors. As a means to examine this conflict, we have utilized an in vitro superfusion system to study the effects of DA, norepinephrine (NE), phentolamine (alpha-antagonist), pimozide (DA antagonist), and two DA agonists (apomorphine and bromocryptine) on GnRH release from isolated mediobasal hypothalami from adult male rats. In this dynamic system, graded concentrations of both NE and DA (2.0 nM to 2.0 microM) led to a dose-dependent increase in GnRH output during the 10 min interval that followed each pulse dose of NE (P less than 0.02) or DA (P less than 0.05). The DA-induced GnRH release was reproducible, consistent, and significant over five successive pulses (20 microM) at 30-min intervals (P less than 0.02). Coinfusion of phentolamine (20 microM) prevented the DA (20 microM) induced release of GnRH (P less than 0.03), but pimozide (20 microM) had no significant effect on DA-induced GnRH release (P greater than 0.3). The two DA agonists, apomorphine and bromocryptine, at doses up to 2.0 microM and 200 nM, respectively, had no significant effect on GnRH release. To determine whether DA was causing a direct stimulation of alpha-adrenergic receptors or being enzymatically converted to NE which could then stimulate alpha-receptors to induce GnRH release, rats were injected with sodium diethyldithiocarbamate (DDC) (550 mg/kg BW) ip, 1 h before death. DDC blocks the enzymatic conversion of DA to NE, and this was reflected by a 37% decrease in hypothalamic NE efflux during the superfusion. However, pulses of DA, even in the presence of DDC, were associated with a marked dose-dependent increase in hypothalamic NE efflux, and DDC failed to prevent the subsequent stimulation of GnRH release. We conclude that the apparent DA-induced release of GnRH is most probably attributable to DA-induced release of hypothalamic NE which, in turn, acts through alpha-adrenergic receptors on peptidergic neurons to stimulate GnRH release.
关于多巴胺（DA）是刺激还是抑制促性腺激素释放激素（GnRH）的分泌，以及其作用是否通过α-肾上腺素能受体或多巴胺能受体介导，目前存在争议。作为研究这一争议的手段，我们利用体外超灌注系统，研究了DA、去甲肾上腺素（NE）、酚妥拉明（α拮抗剂）、匹莫齐特（DA拮抗剂）以及两种DA激动剂（阿扑吗啡和溴隐亭）对成年雄性大鼠离体中基底部下丘脑GnRH释放的影响。在这个动态系统中，在每次脉冲剂量的NE（P<0.02）或DA（P<0.05）后的10分钟间隔内，NE和DA的分级浓度（2.0 nM至2.0 μM）均导致GnRH输出呈剂量依赖性增加。DA诱导的GnRH释放在30分钟间隔的连续五个脉冲（20 μM）中是可重复的、一致的且显著的（P<0.02）。酚妥拉明（20 μM）共同灌注可阻止DA（20 μM）诱导的GnRH释放（P<0.03），但匹莫齐特（20 μM）对DA诱导的GnRH释放无显著影响（P>0.3）。两种DA激动剂，阿扑吗啡和溴隐亭，分别在高达2.0 μM和200 nM的剂量下，对GnRH释放无显著影响。为了确定DA是直接刺激α-肾上腺素能受体，还是被酶促转化为NE，然后刺激α受体诱导GnRH释放，在处死前1小时腹腔注射二乙基二硫代氨基甲酸钠（DDC）（550 mg/kg体重）。DDC可阻断DA向NE的酶促转化，这在超灌注期间下丘脑NE流出量减少37%中得到体现。然而，即使在存在DDC的情况下，DA脉冲仍与下丘脑NE流出量的显著剂量依赖性增加相关，并且DDC未能阻止随后的GnRH释放刺激。我们得出结论，明显的DA诱导的GnRH释放很可能归因于DA诱导的下丘脑NE释放，而后者又通过肽能神经元上的α-肾上腺素能受体起作用以刺激GnRH释放。
