L-DOPA affects apoptosis and proliferation of anterior pituitary cells

OGANDO M; ZARATE S; MAGRI ML; GOTTARDO MF; JAITA G; EIJO G; SEILICOVICH A; FERRARIS J; PISERA D

San Francisco

Congreso; 95th Annual Meeting of The Endocrine Society; 2013

L-DOPA affects anterior pituitary cell proliferation and apoptosis L-3,4-dihydroxyphenylalanine (L-DOPA) is released by hypothalamic neurons. Even though L-DOPA is one of the main drugs used as a treatment for Parkinson’s disease, there are not systematic studies about the possible effects of this drug on anterior pituitary function, which can be clinically relevant. We investigated L-DOPA effects on the proliferation and apoptosis of anterior pituitary cells. Our hypothesis is that L-DOPA produces direct effects on anterior pituitary function, including the modulation of proliferation and apoptosis processes. Administration of L-DOPA to ovariectomized female rats (50 mg/kg i.p., 6 h) increased the percentage of hypodiploid anterior pituitary cells (determined by FACS) (% Sub G0-G1, media ± SEM. Control (C): 9.72 ± 0.65; L-DOPA: 12.94 ± 0.56, p<0.01, Student t test), whereas no significant changes were observed in the cell cycle progression. Then, we evaluated the direct effect of L-DOPA on anterior pituitary primary cultures and GH3 cells. Since we have previously observed that dopamine induces apoptosis of lactotropes by an estradiol (E2) dependent mechanism (1, 2), we evaluated de effects of L-DOPA in presence of E2 (10-9 M) or vehicle (ethanol 1ìl/l; VEH). In cultured anterior pituitary cells from ovariectomized rats, L-DOPA  (10-5 M, 6h) decreased the apoptotic index (determined by TUNEL assay. % apoptotic cells, C: 22.34; L-DOPA: 12.82, p<0.01 ×2). This effect was not observed in the presence of E2 (C: 25.74; L-DOPA: 30.30, ×2) In addition, we analyzed the effects of L-DOPA on anterior pituitary cell cycle progression. L-DOPA significantly decreased the percentage of cells in G2-M phase only in the presence of E2 (C: 12.53 ± 0.44, L-DOPA: 8.83 ± 0.43 , p<0.05). In the GH3 cell line, whereas L-DOPA has no effect on the apoptotic index in VEH treated cells (determined by TUNEL assay) (% apoptotic cells C: 1.56; L-DOPA: 0.96, ×2), this drug induced apoptosis in the presence of E2 (C: 0.23%; L-DOPA: 1.52% p<0.05, X2). In summary, our results indicate that L-DOPA affects anterior pituitary cell proliferation and apoptosis, and suggest that treatment with L-DOPA may have consequences in the neuroendocrine system.