Progesterone-Modulation of Estrogen Action: Rapid Down Regulation of Nuclear Acceptor Sites for the Estrogen Receptor

Leavitt, Wendell W.; Cobb, Andrea D.; Takeda, Akihiro

doi:10.1007/978-1-4684-1297-0_4

Cited by 31 publications

(18 citation statements)

References 94 publications

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“…The ability of progesterone to regulate ER expression has been demonstrated in uterine tissue. 16 The effects of Ovx on ER␤ protein expression were similar in S and R rats. Ovx caused an increase in ER␤ expression, and estrogen replacement reversed this effect in both groups.…”

Section: Discussionmentioning

confidence: 89%

Effect of Ovariectomy on Renal Estrogen Receptor-α and Estrogen Receptor-β in Young Salt-Sensitive and -Resistant Rats

2007

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Abstract-This study evaluated the effect of ovariectomy on renal estrogen receptor (ER)-␣ and ER␤ expression in young female Dahl salt-sensitive and salt-resistant rats. Our hypothesis was that estrogen depletion results in an imbalance in ER␣ and ER␤ expression in salt-sensitive rats. Rats were subjected to sham surgery (intact), ovariectomy, and ovariectomy with estrogen replacement. Kidneys were harvested 8 weeks later. Western blot was used to measure ER␣ and ER␤ expression in the cortex and medulla. In intact rats, ER␣ was 2.7-and 4.3-fold higher in salt-sensitive compared with salt-resistant rats in the renal cortex and medulla, respectively. In salt-sensitive rats, ovariectomy caused 42% and 52% decreases in ER␣ and 107% and 314% increases in ER␤ in renal cortex and medulla, respectively. In salt-resistant rats, ovariectomy caused 33% and 150% increases in ER␣ and 107% and 100% increases in ER␤ in renal cortex and medulla, respectively. Estrogen replacement did not alter ER␣ but restored ER␤ expression levels similar to levels in intact rats in both salt-sensitive and salt-resistant rats. Thus, estrogen loss had opposite effects on ER␣ in salt-sensitive (downregulation) and salt-resistant rats (upregulation). We propose that the decrease in ER␣ expression in salt-sensitive rats after estrogen loss alters the balance of renal ERs and may play a role in accelerating the development of hypertension and renal damage.

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Section: Discussionmentioning

confidence: 89%

Effect of Ovariectomy on Renal Estrogen Receptor-α and Estrogen Receptor-β in Young Salt-Sensitive and -Resistant Rats

2007

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“…As progesterone has been shown to inhibit myometrial expression of ER␣ (22)(23)(24) and HOXA10 (25), we used the levels of mRNAs encoding these factors as surrogate markers of progesterone responsiveness. Thus, we assessed whether PR subtype expression influences progesterone responsiveness by determining the relationship between levels of mRNAs encoding PR-A, PR-B, the PR-A/PR-B mRNA ratio, and levels of mRNAs encoding ER␣ and HOXA10 in the two experimental groups (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…This interaction between the ER and PR systems in the myometrial cell may have important implications for estrogen and progesterone control of the pregnant myometrium. Numerous studies in various species have shown that progesterone and estrogen actions on the uterus are influenced by feedback interactions between the PR and ER systems, whereby progesterone decreases estrogen responsiveness by decreasing ER expression, and estrogen increases progesterone responsiveness by increasing PR expression (23,24). In the context of endometrial function this interaction may ensure an optimum physiological outcome (i.e.…”

Section: Discussionmentioning

confidence: 99%

“…To address this issue, we indirectly assessed the level of myometrial progesterone responsiveness in vivo by measuring the extent of ER␣ and HOXA10 expression and their relationship with PR expression. We chose ER␣ because it is generally accepted that uterine ER expression is inhibited by progesterone (22)(23)(24). The homeobox gene, HOXA10, was examined because its expression in the nonpregnant human myometrium is also inhibited by progesterone (25).…”

Section: Discussionmentioning

confidence: 99%

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Progesterone Withdrawal and Estrogen Activation in Human Parturition Are Coordinated by Progesterone Receptor A Expression in the Myometrium

Mesiano

Chan

Fitter

et al. 2002

The Journal of Clinical Endocrinology & Metabolism

341

158

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In human parturition, progesterone withdrawal and estrogen activation are not mediated by changes in progesterone and estrogen levels. Instead, these events could be facilitated by changes in the responsiveness of the myometrium to progesterone and estrogens via changes in PR and ER expression. We hypothesized that functional progesterone withdrawal occurs by increased expression of the type A PR (PR-A), which suppresses progesterone responsiveness, and that functional estrogen activation occurs by increased myometrial expression of ERalpha and/or ERbeta. To test this hypothesis we compared the abundance of mRNAs (assessed by quantitative RT-PCR) encoding PR-A, PR-B, ERalpha, and ERbeta in nonlaboring (n = 12) and laboring (n = 12) term human myometrium. PR-A, PR-B, the PR-A/PR-B mRNA ratio, and ERalpha mRNA were significantly increased in laboring myometrium, whereas ERbeta mRNA was low and unchanged. The PR-A/PR-B mRNA ratio correlated positively with ERalpha mRNA levels in nonlaboring myometrium and with HOXA10 mRNA levels in laboring myometrium. Because progesterone inhibits ERalpha and HOXA10 expression, these findings indicate that myometrial progesterone responsiveness is inversely related to the extent of expression of PR-A relative to PR-B. ERalpha mRNA levels correlated positively with cyclooxygenase type 2 and oxytocin receptor mRNA levels in nonlaboring myometrium, indicating that the increase in ERalpha expression is directly associated with the activation of contraction-associated genes and estrogen responsiveness. These data indicate that in the term human myometrium, responsiveness to progesterone is controlled by the expression of PR-A relative to PR-B and that a significant increase in this ratio underlies functional progesterone withdrawal. Our data also indicate that functional estrogen activation occurs by increased expression of ERalpha and is linked to functional progesterone withdrawal. Interaction between the PR and ER systems in the human myometrium may be critical for the control of human parturition and the coordination of progesterone withdrawal and estrogen activation required for parturition.

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“…A single injection of E 2 stimulates mitosis in the LE and GE, but not in the stroma [5]. In addition, it is well known that P 4 strongly opposes the proliferative effect of estrogens in the uterine epithelium [32], and P 4 inhibits E 2 -induced uterine epithelial proliferation through PR [33]. There is considerable biological evidence for cross-talk between ER␣ and PR signaling pathways [14].…”

Section: Discussionmentioning

confidence: 97%

A Comparative Study of Estrogen Receptors α and β in the Rat Uterus1

Wang

Masironi

Eriksson

et al. 1999

Biology of Reproduction

135

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The uterus is an important target organ for steroid hormones. The effects of these hormones are mediated via specific receptors. The aim of this study was to compare the expression, distribution, and regulation of estrogen receptor (ER) alpha and beta in the rat uterus in order to establish possible different biological roles for the two receptor forms. Ovariectomized rats were treated with either estradiol (E(2)), progesterone (P(4)), or combinations of these for 24 or 48 h. The mRNA levels were measured by solution hybridization. Distribution of the mRNAs and receptor proteins was detected by in situ hybridization and immunohistochemistry. The results showed that ERalpha is the dominating subtype in the rat uterus. E(2) seemed to increase the ERalpha mRNA level in the glandular and luminal epithelium, but it caused a decrease of the immunostaining intensity in the glandular epithelium. P(4) reduced ERalpha expression in luminal epithelium whereas no effect was seen in the glandular epithelium. E(2) or P(4) did not alter the expression of ERbeta, on either the mRNA or protein level. In conclusion, the distribution and regulation of ERalpha and ERbeta differ in the different compartments of the rat uterus. The complex uterine responses to E(2) and P(4) are directly or indirectly mediated by differential cell-specific expression of their receptors. The low expression in the uterus and the limited regulation by gonadal steroids in this study suggest that ERbeta probably plays a minor role in the regulation of uterine physiology.

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Progesterone-Modulation of Estrogen Action: Rapid Down Regulation of Nuclear Acceptor Sites for the Estrogen Receptor

Cited by 31 publications

References 94 publications

Effect of Ovariectomy on Renal Estrogen Receptor-α and Estrogen Receptor-β in Young Salt-Sensitive and -Resistant Rats

Effect of Ovariectomy on Renal Estrogen Receptor-α and Estrogen Receptor-β in Young Salt-Sensitive and -Resistant Rats

Progesterone Withdrawal and Estrogen Activation in Human Parturition Are Coordinated by Progesterone Receptor A Expression in the Myometrium

A Comparative Study of Estrogen Receptors α and β in the Rat Uterus1

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