The Effects of Aging on Molecular Forms of Beta- and Gamma-Endorphins in Rat Hypothalamus

Wilkinson, Charles W.; Dorsa, Daniel M.

doi:10.1159/000124518

Cited by 34 publications

(13 citation statements)

References 18 publications

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“…The HPLC analyses support previous suggestions that there are age-related alterations in the posttranslational processing of opioid precursors [24], Changes in the proces sing of the DYN precursor molecule have been shown in the HT of developing rats [21], In their study, Seizinger et al [21] found that DYN immunoreactivity in 3-day-old rat pups was represented by larger forms than DYN 1-17. In their 'adult' rats (rats weighing 200-220 g or ~70 days old) the larger forms and DYN 1-17 represented about equal amounts of the immunoreactivity.…”

Section: Discussionsupporting

confidence: 81%

“…A previous study [24] however, does not support this possibility, though it does support the contention that there are increased relative amounts of acetylated forms in the hypothalamus. The authors found HPLC profiles of ir-(IEP and ir-NacEP to be highly variable in hypothalamic ex tracts from senescent animals; overall, however, the mean proportion of acetylated to nonacetylated forms was greater in the old animals.…”

Section: Discussionmentioning

confidence: 69%

“…Recently the effects of aging on the molecular forms of a-and y-EP in the hypothalamus (HT) have been studied in 8-and 24-month-old rats [24]. High-performance liquid chromatography (HPLC) analysis of the various forms in dicated that the immunoreactive:bioactive ratio of the EPs increased with increasing age, with N-acetylated forms par ticularly predominant in the 24-month group.…”

mentioning

confidence: 99%

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Beta Endorphin and Dynorphin Levels in Rat Pituitary and Hypothalamus: Age Studies

et al. 1988

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The content of immunoreactive (ir)-β-endorphin, ir-dynorphin 1–17, and ir-dynorphin 1–8 was determined in hypothalamus, anterior pituitary, and neurointermediate lobe of rats 3–24 months of age. In the anterior pituitary ir-β-endorphin showed a progressive rise with age (0.5 ± 0.06 ng/tissue at 3 months to 1.02 ± 0.23 at 24 months); a similar change was seen in ir-adrenocorticotropic hormone content of the same tissues. No age-related change in neurointermediate lobe ir-endorphin content was observed. In the hypothalamus, the ir-β-endorphin content fell progressively from 3 to 18 months, but was restored at 24 months to levels indistinguishable from those at 3 months (16.2 ± 4.3 ng/tissue compared with 11.3 ± 4.0 at 24 months). The ir-dynorphin content did not change progressively over the age span examined, except in the case of anterior pituitary content of ir-dynorphin 1–17 which fell progressively between 3 and 18 months (from 1.65 ± 0.15 ng/tissue at 3 months to 0.73 ± 0.12). Radioimmunoassay following high-performance liquid chromatography analysis of extracts of the tissues showed little variation of the immunoreactive forms with age, with two notable exceptions. In the hypothalamic extracts from 24-month-old rats the ratio of the nonacetylated ir-endorphin to the acetylated ir-endorphin was lower than in equivalent extracts from 3-month-old rats. In anterior pituitary extracts from 3-month-old rats, ir-dynorphin 1–17 appeared as two peaks (putative 6K and 4K species) of approximately equal size. Between 3 and 18 months the smaller form became predominant, so that in extracts from older rats the larger form was not present. These results indicate that aging influences the net synthesis-secretion balance of these opioid peptides differently, between ages and between tissues. Finally, posttranslational processing of some of these peptides differs with age, as indicated by changes in immunoreactive forms observed on high-performance liquid chromatography.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 69%

mentioning

confidence: 99%

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Beta Endorphin and Dynorphin Levels in Rat Pituitary and Hypothalamus: Age Studies

et al. 1988

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“…Consistently, studies carried out in the rat have dem onstrated age-induced changes in [1-endorphin content in the hypothalamus, in the pituitary and plasma [34][35][36], as well as in p-receptor number and in the molecular form of (1-and y-endorphins in the hypothalamus of aged rats [37,38], Accordingly, the present and some other studies have shown that naloxone is unable to modify plasma LH levels in aged male rats [21] and in elderly humans of ei ther sex [39,40].…”

Section: Discussionsupporting

confidence: 53%

Melatonin Treatment Delays Reproductive Aging of Female Rat via the Opiatergic System

et al. 1992

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In female rat age-related reproductive decline is accompanied by progressive impairment of the neuroendocrine mechanisms that regulate LH secretion. The biosynthetic activity of the pineal gland is markedly depressed and the nocturnal secretion of melatonin decreases significantly. The aim of the present study was to evaluate whether the nocturnal administration of melatonin via the drinking water (0.4 µg/ml) throughout the course of aging from 14 to 24 months of age could (1) influence the age-related changes that occur in basal serum levels of LH and in the LH response to GnRH or to naloxone stimulation at 16, 18 and 20 months of age, and (2) delay the onset of the postreproductive constant estrous-anovulatory state as evaluated by the daily recording of vaginal smears and by occurrence of polyfollicular ovaries at 24 months of age. Our results demonstrate that melatonin replacement delays the increase in LH serum levels and the decrease in LH response to GnRH that occur in 18-month-old control animals. Furthermore, they show that melatonin treatment prevents the loss of LH response to naloxone manifested in control rats between 16 and 20 months of age. Melatonin also appears to prevent the progressive increase in the monthly occurrence of estrus phases as well as to decrease the number of rats with polyfollicular ovaries at 24 months of age in comparison to control animals. These results suggest that the age-related decrease in circulating melatonin during the night may contribute to the reproductive decline of aging, and that this effect may involve the central opioid system.

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“…Changes in the processing of hypothalamic POMC have also been reported to occur in middle-aged female mice [53]as well as in old rats [54], suggesting that ontogenetic changes in the processing of brain POMC occur throughout the life-span. Alterations in POMC processing could occur via changes in the processing enzymes.…”

Section: Discussionmentioning

confidence: 99%

Ontogenesis of Proopiomelanocortin and Its Processing to β-Endorphin by the Fetal and Neonatal Rat Brain

Angelogianni

Gianoulakis

2000

Neuroendocrinology

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A number of reports suggest that β-endorphin (β-END) may play an important role in the regulation of cell proliferation and neuronal differentiation. Proopiomelanocortin (POMC), the common precursor ofadrenocorticotropic hormone and β-END, is detected very early in embryonic life in hypothalamic neurons of the developing rat. However, very little is known about the degree to which POMC is processed to β-END during fetal and early postnatal life. Thus, it was the objective of the present study to estimate the hypothalamic content of POMC mRNA, as well as the biosynthesis and posttranslational processing of POMC by hypothalamic neurons on fetal day 20 and on days 1, 8 and 22 of postnatal life. Hypothalamic POMC mRNA, as determined by Northern blot analysis, was higher on fetal day 20 than on postnatal days 1, 8 and 22. A higher rate of incorporation of [³H]phenylalanine into β-END immunoreactive peptides was observed on fetal day 20 than on postnatal day 1. However, the rate of incorporation was significantly increased by day 8 of postnatal life and was similar to that on day 22. POMC was processed to β-lipotropin (β-LPH) and β-END at all ages examined, but the relative proportions of POMC:β-LPH:β-END changed during development. Thus, β-END accounted only for 34.89 ± 6.14% of the total [³H]phenylalanine-labeled β-END immunoreactive peptides on fetal day 20, while it accounted for 57.37 ± 5.20, 62.81 ± 1.38 and 79.25 ± 6.57% on days 1, 8 and 22 of postnatal life, respectively. Thus, POMC is processed to a considerable extent into β-END-sized peptides by the fetal hypothalamus and may influence brain development. Furthermore, the rate of processing of hypothalamic POMC into β-END increases with development, probably due to the increased activity of the enzymes specific for POMC processing.

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The Effects of Aging on Molecular Forms of Beta- and Gamma-Endorphins in Rat Hypothalamus

Cited by 34 publications

References 18 publications

Beta Endorphin and Dynorphin Levels in Rat Pituitary and Hypothalamus: Age Studies

Beta Endorphin and Dynorphin Levels in Rat Pituitary and Hypothalamus: Age Studies

Melatonin Treatment Delays Reproductive Aging of Female Rat via the Opiatergic System

Ontogenesis of Proopiomelanocortin and Its Processing to β-Endorphin by the Fetal and Neonatal Rat Brain

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