INV SUPERIOR JUBILADO
SEILICOVICH Adriana
artículos
Título:
Estrogens induce expression of membrane-associated estrogen receptor á isoforms in lactotropes
Autor/es:
S. ZARATE; G. JAITA; J. FERRARIS; G. EIJO; M. L. MAGRI; D. PISERA; A. SEILICOVICH
Revista:
PLOS ONE
Editorial:
PUBLIC LIBRARY SCIENCE
Referencias:
Lugar: San Francisco; Año: 2012 p. 41299 - 41299
ISSN:
1932-6203
Resumen:
Estrogens are key to anterior pituitary function, stimulating hormone release and controlling cell fate to achieve pituitary dynamic adaptation to changing physiological conditions. In addition to their classical mechanism of action through intracellular estrogen receptors (ERs), estrogens exert rapid actions via cell membrane-localized ERs (mERs). We previously showed that E2 exerts a rapid pro-apoptotic action in anterior pituitary cells, especially in lactotropes and somatotropes, through activation of mERs. In the present study, we examined the involvement of mERa in the rapid pro-apoptotic action of estradiol by TUNEL in primary cultures of anterior pituitary cells from ovariectomized rats using a cell-impermeable E2 conjugate (E2-BSA) and an ERa selective antagonist (MPP dihydrochloride). We studied mERa expression during the estrous cycle and its regulation by gonadal steroids in vivo by flow cytometry. We identified ERa variants in the plasma membrane of anterior pituitary cells during the estrous cycle and studied E2 regulation of these mERa variants in vitro by surface biotinylation and Western Blot. E2-BSA-induced apoptosis was abrogated by MPP in total anterior pituitary cells and lactotropes. In cycling rats, we detected a higher number of lactotropes and a lower number of somatotropes expressing mERa at proestrus than at diestrus. Acute E2 treatment increased the percentage of mERa-expressing lactotropes whereas it decreased the percentage of mERa-expressing somatotropes. We detected three mERa isoforms of 66, 39 and 22 kDa. Expression of mERa66 and mERa39 was higher at proestrus than at diestrus, and short-term E2 incubation increased expression of these two mERa variants. Our results indicate that the rapid apoptotic action exerted by E2 in lactotropes depends on mERa, probably full-length ERa and/or a 39 kDa ERa variant. Expression and activation of mERa variants in lactotropes could be one of the mechanisms through which E2 participates in anterior pituitary cell renewal during the estrous cycle.