Hypothalamic processing of beta-endorphin in female C57BL/6J mice is altered at middle age.
beta-Endorphin (beta-endo) (1-31) is the active opioid peptide product of pro-opiomelanocortin processing. Further post-translational modifications of beta-endo(1-31) yield beta-endo(1-27), (1-26) and their acetylated forms which are considered to be opiate receptor antagonists. Mechanistically, alteration in opiatergic properties is likely to result in the loss of a number of physiological functions including reproductive capacity. The purpose of this study was to determine whether there are changes in the way beta-endo neurones process the peptide with age in female C57BL/6J mice. Pooled extracts of arcuate nucleus (ARC) and preoptic area (POA) of 3- to 4-month-old normally cycling (4-5 days at dioestrus), 12- to 13-month-old irregularly cycling (5-7 days at dioestrus), 23- to 24-month-old acyclic (in persistent dioestrus) animals were subjected to reversed-phase HPLC (n = 4 experiments). Column fractions were assayed for beta-endo-like-immunoreactivity by sequence-specific RIAs. The opiate receptor active as well as opiate receptor antagonist forms of beta-endo were present in both ARC and POA at all three age groups although their ratios varied. beta-Endo(1-31), the active opiate, was the predominant form in young animals. At middle age there was a threefold (P < 0.05, ANOVA) increase in the antagonist forms of beta-endo and this was associated with a significant (P < 0.05, ANOVA) increase in the ratio of antagonist to active forms. This was accompanied by a trend toward an increase in acetylated forms of beta-endo in middle-aged mice. HPLC profiles from hypothalami of old animals more closely resembled those of young females. The increase in the antagonist forms of beta-endo at middle age may contribute to a decline of opiatergic influences in the female C57BL/6J mouse and suggest a mechanism whereby alterations in opiate influence over gonadotrophin control may occur.
Joshi
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Department of Obstetrics and Gynecology, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Bennett
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HP
James
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Tousignant
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Miller
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MM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011863:Radioimmunoassay; D001615:beta-Endorphin / Q000032:analysis / Q000378:metabolism*
D001615:beta-Endorphin