3-methoxy-4-hydroxyphenylglycol-sulfate and 3-methoxy-4-hydroxyphenylglycol-glucuronide

Much evidence indicates that urinary 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG) is an insensitive measure of central norepinephrine metabolism. This conclusion, however, seems to apply mainly to total urinary MHPG, since previous findings point to the possibility that the major proportion of urinary MHPG sulfate originates in the CNS, while most urinary MHPG glucuronide originates in peripheral organs. To examine this hypothesis, experiments were performed by which we altered MHPG turnover in man at two different stages: firstly, strong physical exercise (ergometer) increased the urinary excretion rate of MHPG glucuronide and not that of MHPG-sulfate; secondly, ethanol (l g/kg), which is known to block the metabolism of MHPG to vanilmandelic acid in the liver, increases the urinary excretion rate of the glucuronide and not that of sulfate. Both experiments indicate that alteration of peripheral norepinephrine turnover changes the urinary excretion of MHPG glucuronide only and not that of sulfate, thus providing strong, albeit indirect, evidence for a primarily central origin of MHPG sulfate. Preliminary experiments in 32 depressed patients showed little difference in both MHPG fractions compared with healthy controls, apart from a slightly reduced excretion rate of glucuronide. These findings fail to provide any evidence of central, and only small changes in peripheral norepinephrine metabolism in depression.

Topics: Adult; Brain; Depressive Disorder; Female; Glycols; Humans; Male; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Receptors, Adrenergic; Sex Factors

Topics: Alprazolam; Biomarkers; Depressive Disorder; Glycols; Humans; Methoxyhydroxyphenylglycol; Norepinephrine

A number of arguments support the hypothesis that changes in urinary levels of MHPG sulfate and MHPG glucuronide respectively reflect central and peripheral norepinephrine metabolism (NE) in man. In this line, the daily excretion of both conjugates was determined in 36 depressed women comparatively to 23 healthy women in order to assess the extent and the central or peripheral location of their possible NE dysfunction. About 80% of the patients suffering from depression (6 endogenous, 19 neurotic, 11 reactive depressions) exhibited a central NE defect, as evidenced by low MHPG sulfate, and many of them had probably also diminished sympathetic activity, as suggested by low MHPG glucuronide. Clinical symptoms possibly related to the psychic state (mood alteration) or associated to sympathetic changes (anxiety, motor activity) respectively altered sulfate or glucuronide excretion. Sulfate (S) and glucuronide (G) MHPG excretions were significantly correlated in healthy subjects (r = 0.53, p = 0.01), thus supporting the concept of the functional link between central NE activity and sympathetic function. Such a correlation was not found in depressive patients. However the lack of significant changes in the mean ratio S/G in the patient sub-groups suggests that as in normal subjects, central and peripheral NE activity are linked in depressed patients, but other factors may also modify sympathetic function. Taken together our data show that the separate assay of sulfate and glucuronide MHPG provides a better picture of NE dysfunction in depression than total MHPG measurement.

Topics: Adjustment Disorders; Adult; Aged; Central Nervous System; Depressive Disorder; Female; Glycols; Humans; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Sympathetic Nervous System

Urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) sulfate and glucuronide reflect, in part, central norepinephrine activity while urinary 3-methoxy-4-hydroxymandelic (VMA) reflects peripheral norepinephrine activity. Urinary MHPG and VMA were measured, together with homovanillic acid (HVA), in 20 symptomatic and seven asymptomatic postmenopausal women and 10 premenopausal control women. Urinary HVA reflects, in part, central dopamine metabolism. After nine of the symptomatic women were treated for 2 months with 0.625 mg of conjugated estrogens, urinary catecholamine measurements were repeated. Serum estrogen levels were not different in symptomatic and asymptomatic patients. Urinary MHPG, VMA, and HVA were similar in symptomatic women before and after estrogen treatment and were not different from levels of asymptomatic postmenopausal and control subjects. The ratios of MHPG:VMA, MHPG:HVA, and VMA:HVA also were similar. While body weight and estrogen did not correlate with urinary catecholamines, there was a significant positive correlation between MHPG and age in postmenopausal subjects (r = 0.56, p less than 0.005).

Topics: Adult; Age Factors; Aged; Central Nervous System; Dopamine; Estradiol; Estrogens; Estrone; Female; Homovanillic Acid; Humans; Menopause; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Vanilmandelic Acid

The aim of our study was to investigate the endogenous origin of the three forms of 3-methoxy-4-hydroxyphenylglycol (MHPG) present in human urine and to further examine the hypothesis of an independent (peripheral or central) origin of glucuronide and sulfate conjugates. The urinary levels of free, sulfate, and glucuronide MHPG were determined in control subjects under normal conditions in relation to age, sex, and diet and in two experimental situations known to alter sympathetic activity. The mean daily excretion of total MHPG in a group of 14 men and 14 women was 1780 +/- 122 micrograms, with the free, sulfate, and the glucuronide representing 8% +/- 0.5%, 40% +/- 1.5%, and 52% +/- 1.6%, respectively. No influence of sex, age, or diet was observed on any form. Strong physical activity and anticipatory stress increased norepinephrine excretion and selectively increased MHPG glucuronide levels without changing the free or the sulfate excretion. We conclude that the total amounts of free, sulfate, and glucuronide MHPG found in urine originate from endogenous body pools with no interference of dietary components. The sympathetic nervous system seems to be the main source of glucuronide and arguments are given supporting the central origin of sulfate.

Topics: Adult; Aged; Aging; Diet; Female; Glycols; Humans; Male; Methoxyhydroxyphenylglycol; Middle Aged; Norepinephrine; Physical Exertion; Sex Factors; Stress, Psychological