The Novel Isoform of the Progesterone Receptor cDNA in the Human Testis and Detection ofIts mRNA in  the Human Uterine Endometrium

Hirata, Shuji; Shoda, Tomoko; Kato, Junzo; Hoshi, Kazuhiko

doi:10.1159/000055286

Cited by 35 publications

(17 citation statements)

References 15 publications

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“…A switch from one isoform of PR to another is yet to be confirmed in the cycling endometrium but could be evidence for the hypothesis that similar processes regulate menstruation and parturition through the ER-dependent regulation of PR isoforms. Recent data suggest that an additional isoform of PR (called PR-S) apparently exists in the endometrium that could be the surface PR isoform although to our knowledge, these data have yet to be confirmed (Hirata et al 2000). Indeed, using RT-PCR, we have been unable to confirm the presence of PR-S in our endometrial samples (data not shown).…”

Section: Discussionmentioning

confidence: 58%

Quantitative histomorphometric analysis of gonadal steroid receptor distribution in the normal human endometrium through the menstrual cycle

Taylor

Guzail

Wahab

et al. 2005

Histochem Cell Biol

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The aim of this study was to test the hypothesis that the distribution of oestrogen receptor beta (ERbeta) and androgen receptor (AR) are related to cell proliferation or correlated with the expression of progesterone receptor (PR) or oestrogen receptor alpha (ERalpha) in the normal human endometrium. Immunohistochemical distribution of immunoreactive ERbeta in well-characterised menstrual cycle biopsy samples was lowest in proliferative endometrial glands, highest in early secretory phase glands and maintained at approximately 20% throughout the rest of the menstrual cycle and was closely correlated with stromal AR and stromal ERbeta expression. Stromal ERbeta was not significantly altered until the menstrual phase of the cycle and was not correlated with the expression of any other antigen in the stroma or endometrial glands except stromal AR. By contrast, glandular AR immunoreactivity was below 5% early in the cycle, increased during the secretory phase and showed strong expression just before menstruation. PR and Ki-67 expression showed strong positive correlations, indicating that PR may be a potent regulator of endometrial proliferation. These data suggest that glandular ERbeta expression is closely associated with a functional secretory role whereas glandular ERalpha and PR are associated with proliferation; glandular AR expression may be the switch required for menstruation.

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Section: Discussionmentioning

confidence: 58%

Quantitative histomorphometric analysis of gonadal steroid receptor distribution in the normal human endometrium through the menstrual cycle

Taylor

Guzail

Wahab

et al. 2005

Histochem Cell Biol

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“…Consequently, PR‐B is an activator of transcription and PR‐A is a transcriptional repressor 41,43‐45. In addition, there are several truncated forms of PR as well as splice variants that may have an impact on progesterone sensitivity 46‐51. Thus, the true tissue responsiveness to progesterone is dependent on the subtype and the expression level of the progesterone receptor.…”

Section: Progesterone Receptors and Their Role In “Functional” Progesmentioning

confidence: 99%

Mechanisms Underlying “Functional” Progesterone Withdrawal at Parturition

Brown

Leite

Strauss

2004

Annals of the New York Academy of Sciences

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Progesterone is a major factor maintaining uterine quiescence throughout pregnancy. In most species, peripheral progesterone levels decline before initiation of labor, and treatments that inhibit progesterone synthesis or action cause termination of pregnancy and/or premature deliveries. These findings suggest that progesterone withdrawal is required for activation of myometrial contractions. However, in humans, circulating progesterone levels remain elevated until birth, which leads to the notion that a "functional" progesterone withdrawal occurs before parturition. The apparent loss of progesterone sensitivity at term could be a consequence of several different mechanisms including: (1) the catabolism of progesterone in the uterus into inactive compounds; (2) alterations in progesterone receptor (PR) isoform ratios; (3) changes in cofactor protein levels affecting PR transactivation; and (4) inflammation-induced trans-repression of PR by nuclear factor kappaB. All of these mechanisms are potentially capable of decreasing uterine progesterone responsiveness at term, thus enabling the expression of pathways that originally were blocked by progesterone in early pregnancy. However, the specific uterine genes whose transcription is directly controlled by PR, and thus affected by "functional" progesterone withdrawal, remain to be identified.

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“…These include PR-S and PR-T originally cloned from a human testicular cDNA library with transcripts demonstrated in human endometrium (16,17). The transcripts are characterized by novel noncoding 5Ј exons (S, T) derived upstream of exon 1 of the nuclear PR followed by sequence for exons 4 -8.…”

mentioning

confidence: 99%

Progesterone stimulates mitochondrial activity with subsequent inhibition of apoptosis in MCF-10A benign breast epithelial cells

Behera

Dai

Garde

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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As an example, progesterone levels correlate with increased epithelial cell proliferation, but there is discordance between the dividing cells and the cells with nuclear progesterone receptor expression. The release of paracrine growth factors from nuclear receptor-positive cells has been postulated as a mechanism, since in vitro studies show a lack of growth effect by progesterone in breast epithelial cells lacking nuclear receptors. This study examined possible nongenomic effects of progesterone in breast epithelia by using MCF-10A cells known to lack nuclear progesterone receptor expression. Treatment for 30 -60 min with progesterone or the progestin, R5020, increased mitochondrial activity as shown by an increase in mitochondrial membrane potential (hyperpolarization) with a concordant increase in total cellular ATP. The reaction was inhibited by a specific progesterone receptor antagonist and not affected by the translation inhibitor cycloheximide. Progestin treatment inhibited apoptosis induced by activation of the FasL pathway, as shown by a decrease in sub-G 1 cell fraction during fluorescence-activated cell sorting and a decrease in caspase 3/7 levels. Progestin treatment did not alter the cell cycle over 48 h. Our study demonstrates a nongenomic action of progesterone on benign breast epithelial cells, resulting in enhanced cellular respiration and protection from apoptosis.progesterone; MCF-10A cells; mitochondria; apoptosis; cellular respiration PREVIOUS STUDIES HAVE SHOWN a discordance between the proliferative action of progesterone in the breast and the content of nuclear progesterone receptors (PR-B and PR-A) in breast epithelial cells. As examples, the mitotic rate of breast epithelial cells is greatest in the progesterone-dominant luteal phase (44). Exogenous administration of estrogen plus progestin results in greater breast epithelial proliferation than estrogen alone (15, 18). The progesterone receptor knockout (PRKO) mouse, an excellent model for the function of nuclear PR in mammary gland development, supports a proliferative role. PR-B is primarily responsible for gland development, with PRKO-B mice showing less extensive ductal development and lack of alveolar terminal end buds (7,29). In contrast to these physiological effects, very few breast epithelial cells appear to express nuclear PR. In immunocytochemical studies of human breast tissue, from 6 to 13% of ductal epithelial cells express PR (6, 37), with the two PR isoforms, B and A, typically localizing in the same cell (14). Immunocytochemical analysis of proliferation by detection of Ki67 antigen in human breast or autoradiographs of [ 3 H]thymidine incorporation in rodent mammary samples show nuclear PR-expressing cells to be nonproliferating. Adjacent cells lacking nuclear PR expression have greater mitotic activity (23). This disassociation between nuclear PR expression and proliferation led to the hypothesis that nuclear PR-expressing cells regulate proliferation of adjacent cells via the control of paracrine factors (4).This ...

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The Novel Isoform of the Progesterone Receptor cDNA in the Human Testis and Detection ofIts mRNA in the Human Uterine Endometrium

Cited by 35 publications

References 15 publications

Quantitative histomorphometric analysis of gonadal steroid receptor distribution in the normal human endometrium through the menstrual cycle

Quantitative histomorphometric analysis of gonadal steroid receptor distribution in the normal human endometrium through the menstrual cycle

Mechanisms Underlying “Functional” Progesterone Withdrawal at Parturition

Progesterone stimulates mitochondrial activity with subsequent inhibition of apoptosis in MCF-10A benign breast epithelial cells

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