Gene Expression in Endocrine Tissues
(W480) EXPRESSION AND REGULATION OF PROGESTERONE RECEPTOR ISOFORMS IN THE MOUSE FALLOPIAN TUBE AND UTERUS.
Shao, Ruijin1, Weijdegård, Birgitta1, Billig, Håkan1, 1 Göteborg University, Göteborg, Sweden
ABSTRACT- We have previously shown that progesterone receptor (PR) isoform A and B are expressed and regulated by gonadotropins and PR antagonists in the mouse ovarian granulosa cells. In the ovary, both PR isoforms are increased significantly between 6 to 12 h and further decreased at 24 h after hCG stimulation. Treatment with PR antagonist-RU 486 results in decrease in the levels of both receptor isoforms in parallel with activation of caspase-3. In the present studies expression of PR isoforms was examined by Western blot and immunohistochemical analyses in the Fallopian tubes and uteri of immature female mice, and together with activation of caspase-3 in response to gonadotropins and RU 486. We observed that PR-A and PR-B protein levels were significantly increased by eCG treatment, and subsequent hCG treatment significantly decreased the expression of both isoforms in Fallopian tubes and uteri opposite from that in the ovary. Regulation of PR-A protein expression in the Fallopian tubes parallels that of PR-B protein expression during gonadotropin treatment. However, in the uterus, PR-B protein levels were increased and peaked earlier than PR-A protein levels. Furthermore, when the levels of PR-B protein were decreased, PR-A protein expression was further increased. Moreover, treatment with RU 486 resulted in increase in both isoform protein levels correlated positively with increased activation of caspase-3 in both tissues. Interestingly, immunohistochemical analysis revealed that a significant increase of PR immunoreactivity in stroma cells, whereas immunoreactive activated caspase-3 was mainly detected in luminal and glandular epithelium after RU 486 treatment. These observations indicate that the regulation of PR isoform expression is tissue-specific, and that both isoforms have a potential role in female reproductive system in vivo.
KEY WORDS: PR isoforms, activation of caspase-3, Fallopian tubes, uterus, mice