DOWN REGULATION OF LYMPHOCYTES APOPTOSIS IN GIRLS WITH PRECOCIOUS PUBERTY

Abstract

The effects of sexual hormones secretion in children with precocious puberty induce significant somatic and psychological changes, with systemic implications on several organs and tissues. Besides immune system and blood cells are involved in these changes. Recent studies on mice lymphocytes have demonstrated a protection of estrogens against apoptosis Fas-FasL pathway. These data could partially elucidate why autoimmune diseases are more frequent in females adolescents, whereas males have higher mortality associated with infectious diseases. We studied ten girls (age: 4-7 years) affected by idiopathic precocious puberty, with pubertal stage B3-PH3-4. All presented increased bone age/chronological age, increased growth velocity, echographic signs of ovarian and uterine maturation, enhanced FSH, LH and 17-β-estradiol levels. In all the patients pituitary MNR was normal. We also evaluated 10 control girls matched for age, with pubertal stage B1PH1. We studied apoptosis of peripheral lymphocytes, using the technique of stratification on Ficoll. Lymphocytes sensitization to apoptotic death mediated by receptors CD95 and TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) was induced. Lymphocytes were incubated for 24 hours with 11 [mu]g/ml of PHA and for 4 days with 25U/ml of IL-2. Therefore 2x10^5 lymphocytes were cultured in 96-well plates and incubated for 24 hours with 200 ng/ml of CD95, 800 ng/ml of TRAIL and with negative control medium alone. Apoptotic death was detected by MTT and lecture by Orange Acridine. We relieved a reduced lymphocytes apoptosis in girls with precocious puberty versus lymphocytes of control subjects both with CD95 and with TRAIL. Our results support the role of pubertal activation by sex hormones on the immune response and the potential incidence of autoimmune diseases in children with precocious puberty, linked to estrogens protection of lymphocytes against apoptosis.