Estradiol interacts with insulin through membrane receptors to induce an antimitogenic effect on lactotroph cells.
The signaling mechanisms of estrogens interact with those of growth factors to control the pituitary gland functions. The contribution of the membrane bound estrogen receptor in these actions is not fully understood. In this study, we focused on the regulatory action of estradiol in interaction with insulin on the secretory and proliferative lactotroph cell activities from primary pituitary cell cultures. Furthermore, we studied the involvement of ERK1/2, PKC epsilon and Pit-1 in these actions. In serum free conditions, estradiol and estradiol-BSA promoted a differential secretory activity on PRL cells but were unable to induce lactotroph cell proliferation. However, both free and conjugated estradiol were competent arresting the mitogenic activity promoted by insulin. Estradiol, estradiol-BSA and insulin stimuli increased the PKC epsilon, phosphorylated ERK 1/2 and Pit-1 expression, although combined treatments with estradiol/insulin or estradiol-BSA/insulin induced a significant reduction in these levels, in close correlation with the decrease of lactotroph cell proliferation. The pre-treatment with PKC inhibitor BIM significantly inhibited the ERK activation promoted by insulin without modifying the ERK expression levels induced by estradiol or estradiol-BSA. By immuno-electron-microscopy the alpha nuclear estrogen receptor was localized in the plasma membrane of lactotroph cells. These findings suggest that the membrane bound ER participates modulating lactotroph cells proliferation via PKC epsilon, ERK1/2 and Pit-1. The interactions between estradiol and growth factors, inducing both mitogenic and antimitogenic effects, could provide glandular plasticity preventing an over-proliferation induced by growth factors.
Gutiérrez
Silvina
S
Centro de Microscopía Electrónica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Haya de la Torre esq. Enrique Barros, 5000 Córdoba, Argentina. silvina@cmefcm.uncor.edu <silvina@cmefcm.uncor.edu>
De Paul
Ana Lucía
AL
Petiti
Juan Pablo
JP
del Valle Sosa
Liliana
L
Palmeri
Claudia Mariela
CM
Soaje
Marta
M
Orgnero
Elsa Margarita
EM
Torres
Alicia Inés
AI
D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology*; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D052682:Lactotrophs / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D016253:Microscopy, Immunoelectron; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D050611:Sodium-Phosphate Cotransporter Proteins, Type III / Q000378:metabolism
D004967:Estrogens; D007328:Insulin; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; C493588:Slc20a1 protein, rat; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D004958:Estradiol; D051744:Protein Kinase C-epsilon; D048052:Mitogen-Activated Protein Kinase 3