L-3,4-DIHYDROXYPHENYLALANINE (L-DOPA) MODULATES HYPOTHALAMUS-PITUITARY-ADRENAL (HPA) AXIS RESPONSE AT PITUITARY LEVEL

SANTIAGO JORDI ORRILLO; DE DIOS NATALY; MORENO AYALA M A; ZARATE S; GOTTARDO MF; FERRARIS J; PISERA D

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Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2016

L-Dopa is the leading treatment of Parkinson?s disease. Thisdrug crosses the blood brain barrier and is converted to dopamine(DA) by the aromatic L-amino acid decarboxylase (AADC) in thecentral nervous system (CNS) and peripheral tissues. Thus, LDopais co-administrated with peripheral AADC inhibitors in orderto enhance its availability in the CNS. Evidences suggest thatneuroendocrine stress response is altered in Parkinson?s disease.In addition, L-Dopa treatment increases the ACTH and cortisolsecretion probably due to CRH neurons activation by dopaminergicreceptors D1 and D2. The aim of the present research wasto determine the effects of the co-treatment with L-Dopa and aninhibitor of AADC (NSD 1015) in the renewal of corticotropic ce lls.First, the expression of AADC was studied by immunofluorescence.We observed in primary culture of rat anterior pituitary cells theenzyme is expressed in corticotropes. Also, pituitary melanotropesfrom intermediate lobe producing POMC derived peptides expressAADC. Likewise, AtT20 cells (a mouse corticotropic cell line) wereimmunoreactive for AADC. To study the effects of L-Dopa on cellapoptosis, AtT20 cells were incubated with L-Dopa (1mM, 8 h) inthe presence of NSD (1mM). Apoptosis was determined by TUNELassay. L-Dopa increased the percentage of TUNEL-positive cells,but the concomitant inhibition of AADC revealed an antiapoptoticeffect of L-Dopa (C: 3.78; L-Dopa: 5.96; NSD: 3.69; L-Dopa+NSD:2.24, p