性腺刺激ホルモンの分泌調節における脳内アミンの役割に関する研究:1.雌ラットの性腺刺激ホルモン分泌に関するcatecholamines及びacetylcholineの脳内作用部位
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Although there is general agreement on the distribution of catecholamines in the brain, controversies exist with regard to the results of investigations on their physiological roles in the regulation of gonadotropin secretion. In most of the studies, catecholamines were injected into the third ventricle, and the effects of catecholamines on gonadotropin secretion were examined in in vitro experiments. Since these experiments did not allow any precise localization of the sites of action of catecholamines, the present study was undertaken in order to determine where noradrenaline (NA), dopamine (DA) and acetylcholine (ACH) are involved in the regulation of gonadotropin secretion in the limbic-preoptic-hypothalamic system of the female rat.<BR>Wistar female rats which were ovariectomized 2 or 3 weeks earlier and animals showing two consecutive regular 4 day estrous cycles were used for the experiments. Blood samples were taken by heart puncture under light ether anesthesia, and serum LH and FSH were measured by radioimmunoassay.<BR>First, in order to examine the involvement of NA, DA and ACH in the regulation of progesterone-induced gonadotropin release, receptor blockers of NA, DA or ACH, phenoxybenzamine (20 mg/kg body weight, i.p., in 50% ethanol), pimozide (1 mg/kg body weight, i.p., in 0.1 M tartaric acid) or atropine (700 mg/kg body weight, s.c., in saline), respectively, were administered to estrogen (20 μg of estradiol benzoate) and progesterone (2 mg) -treated ovariectomized rats. Injections of 2 mg of progesterone into ovariectomized estrogenprimed rats significantly increased serum LH and FSH concentrations 3, 5 and 8 hr later. Phenoxybenzamine, pimozide or atropine prevented the progesterone-induced LH and FSH release.<BR>Secondly, rats were pretreated with three blockers to determine whether NA, DA and ACH participate in the regulation of gonadotropin release in response to electrochemical stimulation of the medial preoptic area (MPO). Electrochemical stimulation of the MPO (100 μA for 60 sec) in ovariectomized estrogen-primed rats produced a dramatic rise in serum LH with a peak 1.5 hr later and in serum FSH with a peak 4.0 hr later. None of the blockers eliminated this gonadotropin release, although pimozide or atropine reduced serum LH concentrations at 4.0 hr after stimulation. In pentobarbital (35 mg/kg body weight) blocked proestrous rats, electrochemical stimulation (50 i/A for 30 sec) of the MPO induced a marked LH release 1.5 hr later resulting in occurrence of ovulation. The administration of phenoxybenzamine did not change the LH release following MPO stimulation and induction of ovulation.<BR>Thirdly, the sites of action of NA, DA and ACH with respect to LH release in the limbic-preoptic system were determined by intracerebral implantation in ovariectomized estrogen-primed rats. DA or ACH, when implanted unilaterally into the MPO, induced a significant increase in serum LH 5 hr later, whereas NA decreased LH levels. Implantations of NA or ACH into the nucleus of the stria terminalis or the medial amygdala increased serum LH, although the effect of NA into the latter was not statistically significant. Only implantations of NA among the three substances into the lateral septum induced LH release.<BR>The results mentioned above showed that NA, DA and ACH all play, possibly as neurotransmitters, stimulatory roles in the regulation of progesterone-induced gonadotropin release in ovariectomized estrogen-primed rats. Furthermore, it would seem most reasonable to propose that none of the adrenergic, dopaminergic and cholinergic synapses are involved in mediating the effect of electrochemical stimulation of the MPO to the medial basal hypothalamus, and that electrochemical stimulation activates directly LH-RH neurons or LH-RH containing neural elements in the MPO to induce discharge of LH-RH from the axon terminals in the median eminence into portal vessels.
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- 性腺刺激ホルモンの分泌調節における脳内アミンの役割に関する研究:1.雌ラットの性腺刺激ホルモン分泌に関するcatecholamines及びacetylcholineの脳内作用部位