Progesterone regulates several functions through the interaction with its intracellular receptor (PR) which expresses two isoforms with different functions and regulation: PR-A and PR-B. Both PR isoforms have been detected in human astrocytomas, the most common and aggressive primary brain tumours, but their regulation and function are unknown. We studied the effects of estradiol, progesterone and their receptor antagonists (ICI 182,780 and RU 486) on PR isoforms content in U373 and D54 human astrocytoma cell lines, respectively derived from grades III and IV astrocytomas, by Western blot analysis. In U373 cells we also evaluated the effects of PR-A overexpression on cell growth. We observed that in U373 cells estradiol increased the content of both PR isoforms whereas in D54 cells it had no effects. Estradiol effects were blocked by ICI 182,780. In both cell lines, PR isoforms content was down-regulated by progesterone after estradiol treatment. This effect was blocked by RU 486. We observed that overexpression of PR-A significantly diminished the increase in U373 cells number produced after progesterone treatment. Our results suggest a differential PR isoforms regulation depending on the evolution grade of human astrocytoma cells, and an inhibitory role of PR-A on progesterone effects on astrocytomas cell growth.
|Original language||English (US)|
|Number of pages||5|
|Journal||Journal of Steroid Biochemistry and Molecular Biology|
|State||Published - Jan 2009|
Bibliographical noteFunding Information:
This study was supported by CONACyT, México, grant 43224. We thank Academia Mexicana de Ciencias, L’Oréal Foundation and UNESCO for their support to this work. We also want to thank Dr. Andrés A. Gutiérrez and Dr. Diana González-Espinosa from Unidad de Terapia Celular, Instituto Nacional de Rehabilitación, México, for the kind gift of cell lines. We also thank Gabriela González-Agüero from Facultad de Química, Universidad Nacional Autónoma de México for her technical support.
- Human astrocytomas
- ICI 182,780
- Progesterone receptor isoforms
- RU 486