Apoptotic cell death of estrogen activated lactotrophs induced by tamoxifen

AOKI MP; ORGNERO E; AOKI A; MALDONADO CA

TISSUE & CELL

CHURCHILL LIVINGSTONE

Año: 2003 vol. 35 p. 143 - 152

0040-8166

Stimulation and inhibition of lactotroph cells cause remarkable morphological and functional changes. In keeping with these changes,the size of the lactotroph cell population undergoes striking alterations due to proliferation or cell death. Factors involved in the induction ofapoptosis of pituitary cells are not well established. We demonstrated earlier that oestrogens prevent lactotroph cells of female rats to die byapoptosis induced by bromocryptine treatment, a fact that can be reversed in ovariectomised rats. In this study, we developed experimentalmodels for in vivo and in vitro studies to gain further insight on the survival effect of oestrogens on lactotrophs. In rats pretreated withoestrogens, tamoxifen generates a massive cell death by apoptosis as validated by the TUNEL technique and DNA electrophoresis ofpituitary gland. On electron microscope observations, numerous lactotrophs exhibited progressive morphological changes in the nucleicompatible with the apoptotic process. The cells remaining intact also exhibit signs of inhibition due to a significant transformation ofregular lactotrophs in atypical subtypes. In pituitary cell cultures exposed to tamoxifen and oestrogen simultaneously, most of the lactotrophsdisplayed features of apoptosis in the nucleus.The present reports gathered new evidences on the apoptogenic potential of tamoxifen on lactotroph cells, and corroborates the contribution of oestrogens to sustain both a balanced population of lactotrophs and a competent secretory activity. The concept that opposedactivities, such as inhibition and stimulation, can activate apoptosis is also strengthen by these observations