Inverse correlation between circulating levels of TNF-related apoptosis-inducing ligand and 17β-estradiol.
BACKGROUND
The regulation of the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL), a cytokine of the TNF family, playing a key role in the immune surveillance against cancer, is incompletely understood.


OBJECTIVE
The objective of the study was to investigate the potential link between TRAIL and 17β-estradiol.


METHODS
Circulating TRAIL levels were measured by an ELISA in plasma samples (n = 246) of healthy, age-matched (range 30-70 y) men and women and in the sera (n = 180) of females belonging to different physiopathological conditions (childhood, pregnancy, under gonadotropin treatment, menopause) characterized by different levels of circulating 17β-estradiol.


RESULTS
TRAIL plasma levels in women with aged younger than 50 years were significantly lower compared with age-matched men, whereas in woman 50 years old or older, TRAIL levels were significantly higher compared with the age-matched men and with the younger women. Moreover, an analysis of women with different conditions revealed a significant inverse correlation between the serum levels of TRAIL and 17β-estradiol, with the lowest levels of TRAIL being observed during pregnancy and the highest in childhood and in postmenopausal women. Moreover, gonadotropin treatment in women undergoing assisted reproduction was accompanied by an acute decrease of serum TRAIL levels. Finally, in vitro treatment with 17β-estradiol decreased the TRAIL expression levels in peripheral blood mononuclear cells.


CONCLUSIONS
Our data suggest that 17β-estradiol plays a role in regulating TRAIL circulating levels. The demonstration that postmenopausal women exhibit the highest TRAIL levels is of particular interest in light of a previous large study population showing that TRAIL is positively correlated to the overall survival.
Institute for Maternal and Child Health (G.Z., O.R.), Istituto di Ricovero e Cura a Carattere Scientifico "Burlo Garofolo," 34137 Trieste, Italy; and Department of Morphology, Surgery, and Experimental Medicine and Laboratorio per le Tecnologie delle Terapie Avanzate Centre (V.T., E.M., G.B., R.M., P.S.) and Department of Medical Sciences (S.V.), Department of Biomedical and Specialist Surgical Sciences (C.C.), and Menopause and Osteoporosis Centre (G.B.), University of Ferrara, 44121 Ferrara, Italy.
Giorgio
G
Zauli
Veronica
V
Tisato
Elisabetta
E
Melloni
Stefano
S
Volpato
Carlo
C
Cervellati
Gloria
G
Bonaccorsi
Oriano
O
Radillo
Roberto
R
Marci
Paola
P
Secchiero
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D012737:Sex Factors; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*; D055815:Young Adult
D053221:TNF-Related Apoptosis-Inducing Ligand; D004958:Estradiol