Chronic diseases are often
accompanied by inflammatory and degenerative processes. Estrogens have
repeatedly been found to be involved in these processes. Testosterone (T) is
the main precursor of estrogen in the brain and T replacement in chronic
diseases has become important in recent years, prompting research on new
T-conjugated molecules. We recently synthesized three new molecules including
unsaturated fatty acid esters: T-linoleate (TL), T-oleate (TO) and T-eicosapentanoate
(TEPA). These substances were s.c. administered for 7 days to intact male rats
subjected to the formalin test (FT). Three other groups were included as
comparisons: NAIVE, receiving no substance, OIL, treated with almond oil
(vehicle), and TN, treated with T-undecanoate, a saturated fatty acid. Spontaneous behaviors and
pain-induced responses were determined during the FT, hormones (T and
dihydrotestosterone, DHT) were determined in blood, while estrogen receptors
(ERα and β) were detected at the genomic
and proteomic levels in the hippocampus, hypothalamus and spinal cord. In the
hippocampus, ERα and ERβ mRNA levels were increased
respectively by TN and TL treatments with respect to OIL, whereas the
hypothalamus TO and TL caused a decrease of ERα mRNA levels. At the proteomic level,
TO, TL and TEPA decreased the levels of ERα in the hypothalamus, whereas TEPA
decreased ERβ in the
spinal cord, hippocampus and hypothalamus. There was no effect of treatment on
the spontaneous behaviors, while the TO and TL groups showed lower pain-induced
behaviors (paw jerk frequency and licking duration) than the OIL group. TN
increased paw jerk frequency and decreased licking duration with respect to
OIL. The treatments had no effect on T and DHT plasma levels. These results
clearly indicate the possibility of pain and ER modulation by T-esters.