| Summary: | 博士 === 國立陽明大學 === 生理學研究所 === 90 === The secretion of prolactin (PRL) is mainly regulated by the inhibitory input from the hypothalamus and dopamine (DA) is the well-accepted PRL-inhibitory hormone. Nevertheless, its secretion is also stimulated by a group of putative PRL-releasing factors (PRFs), e.g., thyrotropin-releasing hormone (TRH), oxytocin, vasopressin, vasoactive intestinal peptide, angiotensin II (AII), a newly discovered prolactin-releasing peptide (PrRP), etc. None of them, however, fulfills all criteria of a hypothalamic releasing hormone. In this thesis, the roles of AII, TRH and PrRP as the potential PRL-releasing hormone as well as their possible relationship with the tuberoinfundibular dopaminergic (TIDA) neuronal activity were assessed.
Adult, ovariectomized and estrogen-primed rats implanted with intracerebroventricular (i.c.v.) cannulae or intratrial catheters were used in the study. Experimental rats were pretreated with daily injection of antisense oligodeoxynucleotide (ODN, 10 g/3 l, i.c.v.) against the mRNA of angiotensinogen, TRH or PrRP for two days. Artificial cerebrospinal fluid or the sense ODNs were used as the control. Both serial blood sampling through the intratrial catheter and micropunch of brain tissue after decapitation were adopted. Plasma or serum PRL levels were determined by radioimmunoassay. The TIDA and nigrostriatal (NS) DA neuronal activities were determined by measuring the major metabolite of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), in the punched median eminence (ME) and striatum (ST), respectively.
Animals pretreated with antisense ODN (10 g/rat/day. for 2 days; i.c.v.) against the mRNA of either angiotensinogen or TRH significantly attenuated the estrogen-induced afternoon PRL surge from 1400 to 1700 h. Replacement injection of either AII or TRH (1 g/rat at 1400 h; i.v.) restored the surge. On the other hand, the effect of PrRP antisense ODN was not significant. Moreover, none of the antisense ODN treatments significantly affected the basal and diurnal changes of TIDA neuronal activity.
Both systemic and central effects of the newly discovered PrRP were also determined in this study. Systemic injection of PrRP (1 and 10 g/rat; i.v.) stimulated PRL secretion in ovariectomized, estrogen-treated rats similar to the effect of TRH. Pretreatment of a dopamine D2 receptor antagonist, sulpride (1 g/rat; i.v.), potentiated the stimulatory effect of both PrRP and TRH on PRL secretion. Central administration of PrRP (0.1-1000 ng/rat; i.c.v.) stimulated the TIDA, but not NSDA neuronal activity in 15 minutes. Serum PRL level, however, was not significantly changed. Similar treatment of TRH (10 ng/rat; i.c.v.) stimulated and inhibited TIDA neuronal activity and serum PRL at 30 min, respectively.
In summary, both endogenous AII and TRH may play a significant role as a PRF in the estrogen-induced afternoon PRL surge. While PrRP may also affect the secretion of PRL, its physiological role is unascertained.
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