Alpha1-adrenergic receptor blockade blocks LH secretion but not LHRH cFos activation.
Long-standing pharmacological evidence supports a role of alpha-noradrenergic receptors in regulating LH release, yet little is known of the action of these receptors on LHRH neurons at the cellular level. We conducted a series of studies aimed at examining the effects of alpha-adrenergic receptor blockade on LH secretion and the cellular activation of LHRH neurons on proestrus. Our initial study used an irreversible alpha-receptor blocker, phenoxybenzamine (alpha1 > alpha2). A group of proestrous rats were treated with phenoxybenzamine at doses of 20 mg/kg, intraperitoneally, or 2, 10 and 20 mg/kg, intravenously, and compared with vehicle injected controls. Phenoxybenzamine administered intraperitoneally did not completely block the LH surge in all animals, whereas all intravenous doses consistently blocked the LH surge. cFos activation of LHRH neurons, on the other hand, was either unaffected or only slightly reduced by phenoxybenzamine treatment intraperitoneally. The effects of intravenous phenoxybenzamine were different, in that at all dose levels phenoxybenzamine completely blocked the LH surge and reduced by approximately half, the cFos activation in LHRH neurons (independent of dose). The effects of intravenous phenoxybenzamine could be mimicked by substitution of prazosin (an alpha1 antagonist, 4 mg/kg), but not idazoxan (an alpha2 antagonist, 1 mg/kg), administered intravenously at 11.00 h and 13.00 h on proestrus. These data provide evidence that noradrenergic systems operating through alpha1-receptors in the neuronal chain leading to the LH surge, while critical for the release of LHRH at the time of an LH surge, are not responsible for the cFos transcriptional changes in LHRH neurons that accompany the natural LH surge.
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Department of Neurobiology, University of Pittsburgh, PA 15261, USA.
Berghorn
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Smith
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Hoffman
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D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D007986:Luteinizing Hormone / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010643:Phenoxybenzamine / Q000494:pharmacology; D011359:Proestrus / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012636:Secretory Rate / Q000187:drug effects
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D016760:Proto-Oncogene Proteins c-fos; D010643:Phenoxybenzamine; D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone