Corticotroph Function Is Modulated By L-3,4-dihydroxyphenylalanine (L-Dopa)

ORRILLO, SANTIAGO JORDI; DE DIOS, NATALY; DE FINO, FERNANDA; FERRARIS, JIMENA; PISERA, DANIEL

Chicago

Congreso; Mentoring and Poster Reception. ENDO 2018; 2018

Endocrine Society

L-Dopa is the leading treatment for Parkinson?s disease (PD). This drug exerts a therapeutic effect through its conversion to dopamine (DA) by aromatic L-amino acid decarboxylase (AADC) in the central nervous system. Thus, L-Dopa is co-administrated with peripheral AADC inhibitors which prevent its metabolism outside the blood brain barrier. Psychiatric disturbances, such as depression, are frequently developed in patients under treatment for PD. Disruptions in the neuroendocrine response to stress, which is orchestrated by the Hypothalamus-Pituitary-Adrenal axis, have been involved in the development of depression. Our general hypothesis propounds that treatment with L-Dopa plus peripheral AADC inhibitors generate an inadequate response to stress. In this study, we investigated the direct effects of these drugs on the function of corticotrophs. Since DA is deaminated by monoamine oxidase (MAO) to produce H2O2, we also studied the role of DA oxidation in the actions of L-Dopa on corticotroph cells renewal. In first place, we studied the metabolism of L-Dopa evaluating the production of DA and Dopac in a mouse corticotroph cell line, AtT20. We found DA and Dopac production (HPLC) only when cells were incubated with L-Dopa (1 and 10 µM; 2 h, p