Lignans in man and in animal species

Abstract

In our laboratories, for several years, two phenolic compounds have been detected during gas chromatographic-mass spectrometric analysis of urinary steroid extracts from human and animal species. Although features of the mass spectra of their trimethylsilyl (TMS) ether derivatives resembled those of oestrogens, they were atypical of steroids. The possibility that they were artefacts of the isolation procedures was discounted after careful studies with blanks, by varying the extraction method and because they were present almost exclusively as conjugates of glucuronic acid. Several of the general characteristics of the unknown compounds were reported after one (referred to as compound 180/442) was found to have a cyclic pattern of excretion during the menstrual cycle of an adult vervet monkey (Fig. 1). An investigation of the nature and distribution of the compounds has shown them to be urinary constituents in humans, baboons, vervet monkeys and rats, and further related compounds have been detected, so far only in vervet monkey urine. We now report spectroscopic and chemical studies that show the two original compounds to be lignans, which have a 2,3-dibenzylbutane skeleton as their basic structure. Unlike all previously known natural lignans, invariably of plant origin, the two mammalian compounds carry phenolic hydroxy groups only in the meta position of the aromatic rings.

The excretion of lignans in rats — evidence for an intestinal bacterial source for this new group of compounds

“…The observations of a cyclic pattern of excretion of HBBL and HBBD during the menstrual cycle of humans [3,5,6 81 and monkeys [ 71 suggested initially that they were produced by the ovaries or influenced by ovarian function. Using the rat however, we have unequivocally demonstrated that lignans are not formed in the ovaries but are biosynthesised by intestinal bacteria, resembling therefore vitamin K synthesis.…”

“…On a body weight basis the daily urinary excretion of the lignans HBBL and HBBD considerably exceeded (5-20-fold) the amounts found in humans [3,5,6] and there was some evidence to indicate a sex difference in the excretion of these compounds; female rats excreting larger amounts of HBBL and smaller amounts of the unknown diphenolic compound compared with male animals. Such differences are not uncommon in rats, steroid metabolism is characterised by qualitative differences between the male and female [ 151, however, in view of the limited number of measurements, additional data are required to confirm this observation.…”

“…Earlier studies in the human suggested the ovaries as a possible source oflignans [3,6,8]. This hypothesis was tested by measuring the excretion of lignans before and after the removal of the ovaries from normal rats.…”

“…The first lignans to be identified in humans and monkeys were described in [3,4], their structures differing from all known plant lignans in having me&substitution in the benzyl groups. The two principal lignans identified were 2,3-bis(3'-hydroxybenzyl)butyrolactone (HBBL) and 2,3&(3'hydroxybenzyl)-butane-1,4diol…”

“…The quantitative excretion of HBBL and HBBD was found to exhibit a cyclic pattern during the menstrual cycle of humans [3-61 and monkeys [7], maximum excretion occurring in the luteal phase and elevated levels were found in urine collected during early pregnancy [6]. Circumstantial data suggested lignans were possibly of ovarian origin or their production was modulated by ovarian function [3]. HBBL was also identified in human pregnancy and suggested to be of ovarian source or produced by ovarian stimulus [8].…”