In vitro regulation of immunoreactive beta-endorphin secretion from adult and fetal hypothalamus by sequential stimulation with corticotropin-releasing hormone.
Previous work has shown corticotropin-releasing hormone (CRH) stimulation of beta-endorphin (END) secretion from hypothalamus. We tested the hypothesis that CRH stimulation of beta-END (measured by radioimmunoassay) from hypothalamic explants is dependent on: (1) ovine CRH dose, (2) pattern and sequence of CRH stimulation, (3) androgen status, and (4) hypothalamic age. Hypothalami from adult male rats and day 17 fetal rats were studied. In adult hypothalami, CRH-stimulated immunoreactive (IR)-beta-END secretion with 10(-7) M was greater than that with 10(-8) M CRH and showed dose-dependent stimulation. Serial stimulation for 20 min by 10(-8) M CRH followed by a 40 min interval without CRH stimulation resulted in a brief stimulation of secretion of IR-beta-END and also secretion of IR-alpha-melanocyte-stimulating hormone (MSH), another peptide derived from pro-opiomelanocortin, the precursor of beta-END. Subsequent stimulation with 10(-6) M CRH showed a desensitization to stimulation despite readily releasable pools of IR-beta-END shown by potassium-induced depolarization. In addition, prolonged stimulation for 1 h with 10(-7) M CRH or increasing concentrations of CRH produced a sustained increase in IR-beta-END release as long as CRH was present. Dihydrotestosterone treatment had no effect on basal nor CRH-stimulated IR-beta-END release in orchiectomized rats. The pattern of IR-beta-END secretion from fetal hypothalamic explants exposed briefly (20 min) or for a prolonged period (1 h) to CRH was similar to that from adult explants. These results demonstrate that: (1) CRH-stimulated IR-beta-END secretion from hypothalamus is dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)
Kapcala
L P
LP
Department of Medicine, University of Maryland School of Medicine and Hospital, Baltimore 21201.
Weng
C F
CF
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D011247:Pregnancy; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D000521:alpha-MSH / Q000494:pharmacology; D001615:beta-Endorphin / Q000276:immunology / Q000378:metabolism*
D000521:alpha-MSH; D001615:beta-Endorphin; D003346:Corticotropin-Releasing Hormone