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Serotonergic mediation of a negative feedback effect of estrogen on luteinizing hormone release in ovariectomized
1Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Abstract:
Effects of the serotonin receptor antagonists ketanserin, metergoline, and methysergide on LH release were tested in ovariectomized (OVX) rats pretreated with estradiol benzoate (EB) (5 micrograms/100 g BW) on each of the 2 days preceding the experiment. LH concentration measured by RIA in plasma samples obtained at 10 min intervals was analyzed using the PULSAR computer program to identify and characterize pulses observed in the LH profile of each rat individually. Multiple pulses were identified in seven of seven OVX rats but in only two of eight OVX rats primed with EB. Multiple pulses were identified in OVX EB-primed rats pretreated with ketanserin (six of seven), metergoline (three of seven), and methysergide (six of eight). Administration of the serotonin (5HT) agonist quipazine (2 mg/kg iv) to OVX rats inhibited pulsatile LH release and depressed mean plasma concentrations for approximately 45 min. This inhibitory response was antagonized by pretreatment of the OVX animals with ketanserin. These results suggest that 1) quipazine inhibits pulsatile LH release in OVX rats by a serotonin2 receptor mechanism; and 2) the inhibitory effect of estrogen on pulsatile LH release may also be mediated, at least in part, via 5HT2 systems.
Insights
Estradiol benzoate inhibits luteinizing hormone (LH) release in ovariectomized rats, an effect mediated by serotonin 5-HT2 receptors. Serotonin receptor antagonists block this estrogen-induced inhibition.
Area of Science:
- Neuroendocrinology
- Reproductive Endocrinology
- Serotonin receptor pharmacology
Background:
- Estrogen plays a crucial role in regulating reproductive functions, including the pulsatile release of luteinizing hormone (LH).
- Serotonin (5-HT) is implicated in modulating neuroendocrine pathways, potentially influencing LH secretion.
Purpose of the Study:
- To investigate the role of serotonin receptors in mediating the inhibitory effects of estradiol benzoate (EB) on LH release in ovariectomized (OVX) rats.
- To determine if serotonin receptor antagonists can block the EB-induced suppression of pulsatile LH release.
Main Methods:
- Ovariectomized rats were pretreated with estradiol benzoate (EB).
- Administration of serotonin receptor antagonists (ketanserin, metergoline, methysergide) or the serotonin agonist quipazine.
- LH concentrations in plasma were measured using radioimmunoassay (RIA) and analyzed for pulsatile release using the PULSAR program.
Main Results:
- Estradiol benzoate significantly reduced pulsatile LH release in OVX rats.
- Serotonin receptor antagonists (ketanserin, methysergide) restored pulsatile LH release in EB-treated OVX rats.
- The serotonin agonist quipazine inhibited pulsatile LH release, an effect blocked by ketanserin, suggesting a serotonin 5-HT2 receptor mechanism.
Conclusions:
- Estrogen's inhibition of pulsatile LH release in OVX rats is, at least partly, mediated through serotonin 5-HT2 receptors.
- Serotonin 5-HT2 receptor systems are involved in the neuroendocrine regulation of LH secretion by estrogen.
