L-3,4-Dihydroxyphenylalanine (L-DOPA) Modulates Corticotrophs Turnover

Presentation Number: MON 371
Date of Presentation: April 3rd, 2017

Santiago Jordi Orrillo, Nataly de Dios, Mariela Moreno Ayala, Sandra Zárate, Maria Florencia Gottardo, Jimena Ferraris* and Daniel Pisera
University of Buenos Aires-CONICET, Buenos Aires, Argentina

Abstract

Administration of 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 the neuroendocrine stress response is altered in parkinsonian patients treated with L-DOPA. This treatment increases the ACTH and cortisol secretion. 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 expression of the enzyme in corticotrophs. Also, pituitary melanotropes from intermediate lobe producing POMC derived peptides expressed AADC. Likewise, AtT20 cells (a mouse corticotropic cell line) were immunoreactive for AADC. To study the effects of L-DOPA on corticotrophs turnover, AtT20 cells were incubated with L-DOPA (1mM, 8 hs) in the presence of NSD 1015 (1mM). Apoptosis and proliferation were determined by TUNEL and BrdU incorporation, respectively. L-DOPA increased the percentage of TUNEL-positive cells, but the concomitant inhibition of AADC revealed an antiapoptotic effect (C: 4.45%; L-DOPA: 6.82%; NSD 1015: 4.05%; L-DOPA+NSD 1015: 2.31%, p<0.01, c2). L-DOPA diminished the percentage of BrdU-positive cells while co-treatment with NSD 1015 increased the proliferation rate (C: 43.67%; L-DOPA: 38.76%; NSD 1015: 44.73%; L-DOPA+NSD 1015: 51.93%, p<0.01, X2). Our results suggest that L-DOPA per se has an antiapoptotic and proliferative effects on AtT20 cells. Given that these cells express AADC, the actions of L-DOPA observed in the absence of NSD 1015 may be due to its local conversion to DA. These pituitary actions could be implicated in the altered response of HPA axis induced by L-DOPA treatment in parkinsonian patients.

 

Nothing to Disclose: SJO, ND, MM, SZ, MFG, JF, DP