| Summary: | 博士 === 國立陽明大學 === 臨床醫學研究所 === 90 === Prostaglandins (PGs) are a group of paracrine/autocrine factors involved in local control of bodily functions, including the neuroendocrine system. Earlier studies demonstrate that intracerebroventricular injection of PGs stimulate prolactin (PRL) secretions. The response, however, varies among different PGs and conditions. Nevertheless, either intravenous/intrapituitary injections of PGs or infusion of PGs into hypophysial portal vein fail to increase serum PRL levels. In all, PGs seem to stimulate PRL secretion via acting on a suprapituitary site. The mechanism of its action has not been studied in detail.
The secretion of PRL is predominantly inhibited by dopamine (DA) released from terminals of the tuberoinfundibular dopaminergic (TIDA) neurons in the median eminence (ME). A diurnal rhythm of TIDA neuronal activity has been shown to exist in female rats, which is essential for the estrogen-induced afternoon PRL surge. Various factors, e.g., acetylcholine, opioids, serotonin, etc., may involve in the regulation of the TIDA rhythm. Whether the PGs are involved and the underlying mechanisms are evaluated in the study.
In the first series of studies, the involvement of PGs in the diurnal changes of the TIDA neurons and PRL secretion in ovariectomized (OVX) rats treated with estrogen (E2) was determined. Prior treatment of indomethacin (50 mg/kg, subcutaneous) for 24 hours significantly prevented the afternoon decrease of TIDA neuronal activity as determined by 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio in the ME, and blocked the PRL surge. Intracerebroventricular (icv) injection of PGE1 (5 mg/3 ml/rat) at 1000 h significantly lowered the activity of TIDA neurons, while similar treatments of PGD2, PGE2, PGF2a or PGI2 were without effect. In OVX+E2 rats pretreated with indomethacin, PGE1 given at 15, but not 30 or 180 min before decapitation（1500 h）significantly reversed the effect of indomethacin on TIDA neuronal activity, while the blocked PRL surge was not reversed.
Our laboratory has previously shown that central opioidergic, cholinergic and serotonergic neurons are involved in the control of TIDA rhythms and the PRL surge in estrogen-treated OVX rats. Therefore, it was of interest to test if PGs may mediate the effects of central opioidergic, cholinegic and serotonergic neuronal systems in the control of TIDA neuronal system. Treatment with naloxone (10 mg/kg, ip), ketanserin (10 mg/kg, ip) or atropine (5 mg/kg, ip) at either 1200 h or 1400 h prevented the afternoon decrease in TIDA neuronal activity and the PRL surge. Intracerebroventricular injection of PGE1 (5 mg/3 ml/rat) at 1500 h significantly reversed the effects of naloxone and atropine, but not that of ketanserin. In OVX+E2 rats pretreated with indomethacin, icv injection of either nicotine (10 ng/rat) or fentanyl (10 ng/rat) failed to suppress the TIDA neuronal activity or to stimulate the PRL secretion.
With regard to nigrostriatal DA (NSDA) neurons, treatment of indomethacin lowered the basal NSDA neuronal activity, indicating that PGs played a stimulatory role. Centrally administered PGE2 also exhibited an acute stimulatory effect on ST DOPAC/DA ratio. Although PGE1did not have a significant effect in untreated OVX+E2 rats, it significantly stimulated the ST DOPAC/DA in indomethacin-pretreated OVX+E2 rats. Taken together, PGEs may play a stimulatory role in maintaining the activity of NSDA system.
In summary, PGs, especially the E series, may play a significant role in the regulation of central DA systems. The manifestation of diurnal rhythm of TIDA neuronal activity and the afternoon PRL surge in OVX+E2 rats also depend on an intact PG system. It may also mediate the effects of opioid and acetylcholine in controlling the diurnal change of the TIDA neuronal activity.
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