Fig. 1.
Rat estrous cycle and differences in p38, c-fos and ER expression during various stages of the cycle. The average estrous cycle length in rats is 4–5 days. The cycle is subdivided into four phases: proestrus, estrus, metestrus, and diestrus. The proestrus phase begins when progesterone (P4) levels decline as a result of luteolysis and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion from the anterior pituitary. In the adult female rat, preovulatory estradiol (E2), which is produced by ovarian follicles, concentration peaks during the proestrus phase. As a result of the pre-ovulatory E2 surge, ovulation occur during the estrus phase. In proestrus, endometrial stromal cell proliferation, stromal edema, and proliferation of luminal and glandular epithelium with subsequent increase in endometrial thickness take place. Myometrial hypertrophy also is seen during estrus. In the metestrus and diestrus phases, the luminal lining epithelial cells are reduced in height, the stroma becomes denser, and the uterus becomes quiescent with subsequent decreases in endometrial thickness. Overall, p38 strongly is upregulated during proestrus, estrus, and metestrus phases. c-fos is strongly upregulated in proestrus and metestrus and mildly upregulated in estrus. ERα expression is highest during proestrus and lowest in metestrus11,30,31,119.