L-3,4-Dihydroxyphenylalanine (L-DOPA) modulates hypothalamus-pituitary-adrenal (HPA) axis response at pituitary level

ORRILLO SANTIAGO JORDI; DE DIOS NATALY; MORENO AYALA MARIELA; ZÁRATE SANDRA; GOTTARDO MARÍA FLORENCIA; FERRARIS JIMENA; PISERA DANIEL

Mar del Plata

Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica; 2016

LDopa is the leading treatment of Parkinson´s disease. This drug crosses the blood brain barrier and is converted to dopamine (DA) by the aromatic Lamino acid decarboxylase (AADC) in the central nervous system (CNS) and peripheral tissues. Thus, Ldopa is coadministrated with peripheral AADC inhibitors in order to enhance its availability in the CNS. Evidences suggest that neuroendocrine stress response is altered in Parkinson´s disease.In addition, Ldopa treatment increases the ACTH and cortisol secretion probably due to CRH neurons activation by dopaminergic receptors D1 and D2. The aim of the present research was to determine the effects of the cotreatment with Ldopa and an inhibitor of AADC (NSD 1015) in the renewal of corticotropic cells. First, the expression of AADC was studied by immunofluorescence. We observed in primary culture of rat anterior pituitary cells the enzyme is expressed in corticotropes. Also, pituitary melanotropes from intermediate lobe producing POMC derived peptides express AADC. Likewise, AtT20 cells (a mouse corticotropic cell line) were immunoreactive for AADC. To study the effects of Ldopa on cell apoptosis, AtT20 cells were incubated with Ldopa (1mM, 8 h) in the presence of NSD (1mM). Apoptosis was determined by TUNEL assay. Ldopa increased the percentage of TUNEL-positive cells,but the concomitant inhibition of AADC revealed an antiapoptoticeffect of Ldopa. Our results suggest that Ldopa per se has anantiapoptotic effect on AtT20 cells. Given that these cells expressAADC, the actions of Ldopa observed in the absence of NSD maybe due to its local DA conversion. These pituitary actions may beinvolved in the altered response of HPA axis observed in patientswith Parkinson´s disease treated with Ldopa.