Tyrosine hydroxylase and dopamine transporter expression in lactotrophs from postlactating rats: involvement in dopamine-induced apoptosis.
Cessation of lactation causes a massive loss of surplus lactotrophs in the rat pituitary gland. The factors and mechanisms involved in this phenomenon have not yet been elucidated. Besides its inhibitory control on prolactin secretion and lactotroph proliferation, evidence suggests that dopamine (DA) may be a proapoptotic factor for lactotrophs. We therefore tested the proapoptotic effect of DA on pituitary glands from virgin, lactating, and postlactating rats. By measuring mitochondrial membrane potential loss, caspase-3 activation, and nuclear fragmentation, we show that DA induces apoptosis specifically in lactotrophs from postlactating rats. We then determined that this effect was partly mediated by the DA transporter (DAT) rather than the D(2) receptor, as corroborated by the detection of DAT expression exclusively in lactotrophs from postlactating rats. We also observed tyrosine hydroxylase (TH) expression in postlactating lactotrophs that was accompanied by an increase in DA content in the anterior pituitary gland of postlactating compared with virgin rats. Finally, we observed that cells expressing TH coexpressed DAT and cleaved caspase-3. These findings show that DA may play a role in lactotroph regression during the postlactation period by inducing apoptosis. The fact that this process requires DAT and TH expression by lactotrophs themselves suggests that it may be "autocrine" in nature.
Jaubert
Arnaud
A
Laboratoire de Signalisation et Mécanismes Moléculaires de l'Apoptose, INSERM E347, Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux cedex, France. laurence.bresson-bepoldin@bordeaux.inserm.fr.
Drutel
Guillaume
G
Leste-Lasserre
Thierry
T
Ichas
François
F
Bresson-Bepoldin
Laurence
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007774:Lactation / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D052682:Lactotrophs / Q000378:metabolism*; D008954:Models, Biological; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D014446:Tyrosine 3-Monooxygenase; C505410:Casp3 protein, rat; D053148:Caspase 3; D004298:Dopamine