Tissue-Specific Regulation of Rat Estrogen Receptor mRNAs

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Abstract
The estrogen receptor (ER) is present in a wide variety of mammalian tissues and is required for physiological estrogen responses, including estrogen-induced tissue-specific changes in gene expression. We studied the estrogen regulation of the mRNAs encoding the ER in rat uterus, liver, and pituitary. Ovariectomized (21-28 days post surgery) female CD-1 rats were injected daily with 17 .beta.-estradiol (E2, 10 .mu.g/100 g BW) for 0, 1, or 4 h, 1, 3, or 7 days and compared with intact controls. Steadystate levels of ER mRNA were quantified using a human ER cDNA probe. Only one hybridizing species of approximately 6.2 kilobase (kb) was detected in uterine and liver RNA, similar to that observed in MCF7 human breast cancer cells. However, the ER mRNA regulation by E2 differed in direction depending on the tissue examined. In uterus, ER mRNA increased 3- to 6-fold after ovariectomy, and returned to intact levels within 24 h of E2 replacement. In contrast, liver ER mRNA declined 1.5- to 3-fold after ovariectomy and returned to intact levels after 1-3 days of E2. In pituitary tissue two hybridizing forms of ER mRNA were observed, with one species migrating at 6.2 kb, equivalent to the form in other tissues, and a second smaller species at approximately 5.5 kb. The lower molecular weight species varied somewhat in abundance from animal to animal, averaging about 20% of the intensity of the 6.2 kb band. The ER mRNA forms were regulated positively with E2. Pituitary ER mRNA decreased 3-fold after ovariectomy and increased significantly after 4 h of E2 treatment, returning to control levels after 24 h of the hormone. Thus, both tissue-specific forms of ER mRNA and tissue-specific regulation of these forms occur in normal rat tissues.