TITLE:
Effects of Unsaturated Fatty Acid Esters of Testosterone on Neuronal, Behavioral and Hormonal Parameters in Male Rats Subjected to the Formalin Test
AUTHORS:
Anna Petroni, Paolo Fiorenzani, Valentina Tomei, Antonio Garofalo, Francesca Aiello, Daniele Della Seta, Antonio Giordano, Stella Vodo, Ilaria Ceccarelli, Anna Maria Aloisi
KEYWORDS:
Testosterone, CNS, Fatty Acids, Pain, Estrogen Receptors
JOURNAL NAME:
Open Journal of Endocrine and Metabolic Diseases,
Vol.4 No.6,
June
26,
2014
ABSTRACT: 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, asaturatedfatty acid. Spontaneous behaviors and
pain-induced responses were determined during the FT, hormones (T and
dihydrotestosterone, DHT) were determined in blood, while estrogen receptors
(ERαandβ) were detected at the genomic
and proteomic levels in the hippocampus, hypothalamus and spinal cord. In the
hippocampus, ERαand ERβmRNA levels were increased
respectively by TN and TL treatments with respect to OIL, whereas the
hypothalamus TO and TL caused a decrease of ERαmRNA levels. At the proteomic level,
TO, TL and TEPA decreased the levels of ERαin the hypothalamus, whereas TEPA
decreased ERβin 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.