Biphasic effects of progesterone on tuberoinfundibular dopaminergic neuronal activity and prolactin secretion: Possible mechanism of action
| Autor: | Chu-Hui Chen, 陳主慧 |
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| Rok vydání: | 2000 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 88 Progesterone (P4) is one of the major steroid hormones synthesized and secreted from the ovary, and is the hormone directly responsible for the establishment and sustenance of pregnancy. In addition, P4 can exhibit a biphasic effect on the proestrous afternoon prolactin (PRL) surge, viz. facilitation given in the morning of proestrus and inhibition given 24 hours earlier. Previous study from our lab has shown that the facilitative effect of P4 on the PRL surge is accompanied by an advanced decrease in tuberoinfundibular dopaminergic (TIDA) neuronal activity in the afternoon. The objective of the present study was to determine if the inhibitory effect of P4 also involves changes in TIDA neurons. Adult female Sprague-Dawley rats ovariectomized (OVX) for 6 days and implanted with estrogen (E2)-containing capsules for another 6 days were used. P4 (2-20 mg/kg, sc) was given to experimental rats around 0800 h on day 5 and the rats were sacrificed at various time points on day 6. The TIDA neuronal activity was determined by measuring the major metabolite of dopamine, 3,4-dihydrophenylacetic acid (DOPAC), in the median eminence by HPLC-ECD and serum PRL was measured by RIA. P4 given a day earlier significantly inhibited the estrogen-induced afternoon PRL surge. The treatment also prevented the diurnal change of TIDA neuronal activity. Nevertheless, P4 given a day earlier had no significant effect on the facilitative effect of P4 given on the same day of sacrifice. It has been reported that P4 receptor may be activated by a ligand-independent manner such as by dopamine. Nevertheless, central administration of two doses of a dopamine D1 receptor agonist, SKF38393 (0.1 and 1μg) around 0800 h could not mimic the effects of P4 on TIDA neuron and PRL. On the other hand, previous studies from our lab have shown that histamine (H), angiotensin (AII) and neurotensin (NT) all possess stimulatory effects on TIDA neuronal activity, which may be involved in the action of P4. Neurotensin-containing neurons in the arcuate nucleus even contain P4 receptors. Thus, specific antagonists (10μg each), i.e., pyrilamine (H), saralasin (AII) and SR-48692 (NT) were centrally administered in OVX+E2+P4-treated rats at 1200 h and found that all three agents significantly prevented the effect of P4 on TIDA neurons, but not on PRL surge. Using systemic injection SR-48692 (1 mg/kg, ip) also had the same effect. In summary, P4 given a day earlier in OVX+E2-treated rats indeed had an inhibitory effect on the estrogen-induced afternoon surge and its effect may act through activating the TIDA neurons. Although preventing the action of endogenous H, AII or NT could block P4’s effect on TIDA neurons, it could not reinstate the afternoon PRL surge. In conclusion, the inhibitory effect of P4 on PRL secretion may involve dopamine, the PRL-inhibiting hormone, and an undetermined PRL-releasing factor(s). |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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