Differential expression of uterine progesterone receptor forms A and B during the menstrual cycle

https://doi.org/10.1016/S0960-0760(97)00119-2Get rights and content

Abstract

Recent studies suggest that the progesterone receptor isoforms (PR-A and PR-B) activate genes differentially and that PR-A may act as a repressor of PR-B function. Hence, the absolute and relative expression of the two isoforms will determine the response to progesterone. We have measured their relative expression in the uterus of cycling women who underwent endometrial biopsy. PR isoforms were identified on blots of SDS-PAGE gels by reaction with the AB-52 antibody after immunoprecipitation from endometrial extract. Both isoforms were highest in the peri-ovulatory phase, but levels of PR-A were always higher than those of PR-B. The ratio of PR-A to PR-B changed during the menstrual cycle. Between days 2 and 8, PR-B is almost undetectable and the A:B ratio is >10:1. From days 9 to 13, the ratio is about 5:1, and it is about 2:1 between days 14 and 16. Thereafter, PR-B dwindles rapidly and is virtually undetectable at the end of the cycle. In various hypoestrogenic environments, PR-B expression was reduced. However, exogenous estrogens in the follicular phase in the form of oral contraceptives, enhanced PR-B expression. These data support the possibility that progesterone acts through cycle-specific PR isoforms.

References (41)

  • O. Jänne et al.

    Oestrogen-induced progesterone receptor in human uterus

    J. Steroid Biochem.

    (1975)
  • K.B. Horwitz

    Is a functional estrogen receptor always required for progesterone receptor induction in breast cancer?

    J. Steroid Biochem.

    (1981)
  • C.L. Clarke et al.

    Progestin regulation of cellular proliferation

    Endocrinol. Rev.

    (1990)
  • M-J. Tsai et al.

    Molecular mechanisms of action of steroid/thyroid receptor superfamily members

    Ann. Rev. Biochem.

    (1994)
  • K.B. Horwitz et al.

    In situ photo linked nuclear progesterone receptors of human breast cancer cells: subunit molecular weights after transformation and translocation

    Endocrinol.

    (1983)
  • P.A. Boyd et al.

    Seasonal changes in the molecular species and nuclear binding of the chicken oviduct progesterone receptor

    Biochem.

    (1979)
  • G. Shyamala et al.

    Developmental regulation of murine mammary progesterone receptor gene expression

    Endocrinol.

    (1990)
  • L. Tung et al.

    Antagonist-occupied human progesterone B-receptors activate transcription without binding to progesterone response elements and are dominantly inhibited by A-receptors

    Mol. Endocrinol.

    (1993)
  • W.L. Kraus et al.

    Inhibitory cross-talk between steroid hormone receptors: differential targeting of estrogen receptor in the repression of its transcriptional activity by agonist- and antagonist-occupied progestin receptors

    Mol. Cell. Biol.

    (1995)
  • E. Vegeto et al.

    Human progesterone receptor A form is a cell- and promoter-specific repressor of human progesterone receptor B function

    Mol. Endocrinol.

    (1993)
  • Cited by (115)

    • Be quick about it. Endogenous estradiol level, menstrual cycle phase and trait impulsiveness predict impulsive choice in the context of reward acquisition

      2015, Hormones and Behavior
      Citation Excerpt :

      Yet, the present data also show that in the state of heightened E2 (i.e., in the late FP) this hormone–behavior relationship no longer existed, despite a constant PROG level across the follicular phase. This might be explained by other factors like cycle-dependent changes in steroid receptor architecture (Mangal et al., 1997). Further, the actual relationship between E2 and behavioral impulsivity could be non-linear and might be similar to the inverted U-function that has been demonstrated previously for the twofold association of mesolimbic DA and impulsivity (Cools et al., 2009; Smith and Boettiger, 2012).

    • Human Oviduct and Endometrium: Changes over the Menstrual Cycle

      2015, Knobil and Neill's Physiology of Reproduction: Two-Volume Set
    • Steroid Hormone Action

      2013, Yen and Jaffe's Reproductive Endocrinology: Seventh Edition
    • Progesterone receptor targeting with radiolabelled steroids: An approach in predicting breast cancer response to therapy

      2013, Journal of Steroid Biochemistry and Molecular Biology
      Citation Excerpt :

      These nuclear receptors, which specifically bind progesterone and are induced by estrogens, were initially characterized in the mammalian uterus and chick oviduct in the early 1970s, by Sherman [53–56]. PR is expressed in the female reproductive tract, mammary gland, brain, and pituitary gland [57,58]. In many cells estrogens induce expression of PR, and its presence is a common marker for oestrogen action in both research and clinical settings.

    • Differential regulation of endogenous pro-inflammatory cytokine genes by medroxyprogesterone acetate and norethisterone acetate in cell lines of the female genital tract

      2011, Contraception
      Citation Excerpt :

      We were unable to detect the PR-B isoform in any of the cell lines, and thus we postulate that it is the transcriptionally less active PR-A isoform that is present in these cell lines. Indeed, variation in the expression of PR-A and PR-B has previously been reported in the eutopic endometrium during the menstrual cycle [73], with no PR-B detectable during the secretory and early proliferative phases. Similarly, Attia et al. [74] did not detect any PR-B protein in endometriotic tissue and they ascribe the clinically observed resistance of endometriosis to treatment with progestins to this absence of PR-B and to the presence of PR-A.

    • Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception

      2011, Steroids
      Citation Excerpt :

      Thus although all steroid receptors generally appear to function by similar mechanisms, the progestin-specific intracellular actions on target genes via steroid receptors may vary depending of many factors such as those discussed above. The physiological response of a cell to Prog is mediated by the PR, which is expressed in the female reproductive tract, mammary gland, brain, as well as the pituitary gland [131,132]. Prog plays a central role in various reproductive events associated with establishment and maintenance of pregnancy, normal mammary gland development and sexual behaviour [133,134].

    View all citing articles on Scopus

    Current address: Zonagen, Inc., 2408 Timberloch Place, B4 The Woodlands, Texas 77380

    View full text