Evidence for serotonergic stimulation of pituitary beta-endorphin release: preferential release from the anterior lobe in vivo.
Using gel filtration chromatography (Sephadex G-50) and radio-immunoassay for beta-endorphin (beta-END) and beta-lipotropin (beta-LPH) we investigated the site [anterior lobe (AL) vs. intermediate lobe (IL)] for serotonergic control of pituitary beta-END-like immunoreactivity (beta-END-LI) in the rat. Since the secretion of beta-LPH in vitro clearly distinguishes beta-END-LI release by the AL as compared to the IL, we interpreted changes in plasma levels of immunoreactivity resembling beta-LPH to reflect beta-END-LI release from the AL. Following the administration of L-tryptophan (200 mg/kg, 30 min, ip), a serotonin precursor, nearly all of the rise in total plasma beta-END-LI was due to the form of immunoreactivity resembling beta-LPH in molecular size. Similarly, 5-hydroxytryptophan (30 mg/kg, 30 min, ip), a serotonin precursor, and fluoxetine (10 mg/kg, 15 min, ip), a serotonin reuptake blocker, predominantly increased circulating levels of beta-LPH-sized immunoreactivity with little effect on beta-END-sized immunoreactivity. Quipazine (2.5 and 5.0 mg/kg, 30 min, ip), a serotonin receptor agonist, elevated plasma levels of both forms of beta-END-LI; however, the immunoreactive peak coeluting with beta-LPH was primarily affected, being increased 9.5-fold while that resembling beta-END was increased less than 1-fold. Immobilization stress (30 min) dramatically elevated plasma levels of both forms of immunoreactivity, however, a greater relative rise in beta-LPH than beta-END was observed. Intraventricular administration of 5,7-dihydroxytryptamine (75 micrograms, free base, 10 d), a serotonin neurotoxin, lowered plasma levels of both forms of immunoreactivity about equally in stressed animals. Further, dexamethasone, a synthetic glucocorticoid which selectively inhibits AL corticotroph secretion in vitro, attenuated the beta-LPH response to serotonergic activation in vivo. Together, these findings indicate that serotonergic drugs predominantly influence the release of beta-END-LI resembling beta-LPH and further suggest that serotonin neurons preferentially regulate the release of beta-END-LI from AL corticotrophs in vivo.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D004723:Endorphins / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011814:Quipazine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000502:physiology*; D013312:Stress, Physiological / Q000378:metabolism; D014364:Tryptophan / Q000494:pharmacology; D001615:beta-Endorphin; D008083:beta-Lipotropin / Q000378:metabolism
D004723:Endorphins; D005473:Fluoxetine; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D011814:Quipazine; D001615:beta-Endorphin; D003907:Dexamethasone; D014364:Tryptophan; D008083:beta-Lipotropin; D006916:5-Hydroxytryptophan