L-3,4-dihydroxyphenylalanine (L-Dopa) modulates Hypothalamus-Pituitary-Adrenal (HPA) axis response at pituitary level

MORENO AYALA, MARIELA; FERRARIS, JIMENA; DE DIOS, N; GOTTARDO, MARÍA FLORENCIA; ORRILLO, S; ZÁRATE S; PISERA D

Mar del Plata

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

Sociedad Argentina de Investigación Clínica (SAIC)

L-Dopa is the leading treatment of Parkinson?s disease. This drug crosses the blood brain barrier and is converted to dopamine (DA) by the aromatic L-amino acid decarboxylase (AADC) in the central nervous system (CNS) and peripheral tissues. Thus, L-Dopa is co-administrated 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, L-Dopa 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 co-treatment with L-Dopa 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 L-Dopa on cell apoptosis, AtT20 cells were incubated with L-Dopa (1M, 8 h) in the presence of NSD (1M). Apoptosis was determined by TUNEL assay. L-Dopa increased the percentage of TUNEL-positive cells, but the concomitant inhibition of AADC revealed an antiapoptotic effect of L-Dopa (C: 3.78; L-Dopa: 5.96; NSD: 3.69; L-Dopa+NSD: 2.24, p