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 modifi cations of beta-endo(1-31) yield beta-endo(1-27), (1-26) and their ace tylated forms which are considered to be opiate receptor antagonists. Mechanistically, alteration in opiatergic properties is likely to resu lt in the loss of a number pf physiological functions including reprod uctive capacity. The purpose of this study was to determine whether th ere 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 da ys at dioestrus), 12- to 13-month-old irregularly cycling (5-7 days at dioestrus), 23- to 24-month-old acyclic (in persistent dioestrus) ani mals were subjected to reversed-phase HPLC (n=4 experiments). Column f ractions were assayed for beta-endo-like-immunoreactivity by sequence- specific RIAs. The opiate receptor active as well as opiate receptor a ntagonist forms of beta-endo were present in both ARC and POA at all t hree age groups although their ratios varied. beta-Endo(1-31), the act ive opiate, was the predominant form in young animals. At middle age t here 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 accomp anied by a trend toward an increase in acetylated forms of beta-endo i n middle-aged mice. HPLC profiles from hypothalami of old animals more closely resembled those of young females. The increase in the antagon ist forms of beta-endo at middle age may contribute to a decline of op iatergic influences in the female C57BL/6J mouse and suggest a mechani sm whereby alterations in opiate influence over gonadotrophin control may occur.