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Down-regulation of progesterone receptor membrane component 1 (PGRMC1) in peripheral nucleated blood cells associated with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS).

Schuster J, Karlsson T, Karlström PO, Poromaa IS, Dahl N - Reprod. Biol. Endocrinol. (2010)

Bottom Line: The levels of PGRMC1 protein in nucleated peripheral blood cells were quantified by Western blot analysis.PGRMC1 levels did not vary significantly throughout the menstrual cycle.We observed a significant down-regulation of PGRMC1 in postmenopausal women and in patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) when compared to early follicular phase of healthy women.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden. jens.schuster@genpat.uu.se

ABSTRACT

Background: Progesterone receptor membrane component 1 (PGRMC1) is a member of a progesterone-binding complex implicated in female reproduction. We aimed i) to determine the natural expression of PGRMC1 in peripheral nucleated blood cells throughout the menstrual cycle and ii) to investigate any association between PGRMC1 levels in leukocytes and conditions characterized by reduced fertility.

Methods: We analyzed PGRMC1 expression in peripheral leukocytes from 15 healthy cycling women over four weeks. Additionally, we determined PGRMC1 levels in samples from patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) as well as in healthy postmenopausal women and male controls. The levels of PGRMC1 protein in nucleated peripheral blood cells were quantified by Western blot analysis.

Results: PGRMC1 levels did not vary significantly throughout the menstrual cycle. We observed a significant down-regulation of PGRMC1 in postmenopausal women and in patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) when compared to early follicular phase of healthy women.

Conclusion: This study suggests that reduced levels of PGRMC1 in peripheral leukocytes are associated with perturbed ovulatory function.

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Related in: MedlinePlus

Detection of PGRMC1 and β-actin by Western blot analysis in total protein preparations obtained from peripheral nucleated blood cells (PNBC). Representative western blot pictures illustrating detection in (A) healthy cycling women (HF; distinct phases are indicated above), (B-D) PCOS and POF patients and control groups (PM, natural menopausal women; HM, healthy men). Total protein preparations were separated on a 12% SDS-PAGE, transferred to a PVDF membrane and subsequently detected using α-PGRMC1 and α-β-actin antibodies. A protein standard was included and the band sizes are indicated to the left. Bands corresponding to PGRMC1 (green) and β-actin (red) are indicated.
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Figure 1: Detection of PGRMC1 and β-actin by Western blot analysis in total protein preparations obtained from peripheral nucleated blood cells (PNBC). Representative western blot pictures illustrating detection in (A) healthy cycling women (HF; distinct phases are indicated above), (B-D) PCOS and POF patients and control groups (PM, natural menopausal women; HM, healthy men). Total protein preparations were separated on a 12% SDS-PAGE, transferred to a PVDF membrane and subsequently detected using α-PGRMC1 and α-β-actin antibodies. A protein standard was included and the band sizes are indicated to the left. Bands corresponding to PGRMC1 (green) and β-actin (red) are indicated.

Mentions: We obtained eight venous EDTA blood samples from each of 15 healthy women during four weeks. The time spans approximately one menstrual cycle and none of the women were on any hormonal treatment. Serum estrogen and progesterone levels were measured in each sample. Both hormones showed expected and normal profiles over the four weeks period (table 1). The hormone profile, LH surge and first day of menstrual bleeding were used to assign every sample to a distinct day of a standardized 28 day menstrual cycle (table 1). Subsequently, we analyzed PGRMC1 protein levels in total protein preparations derived from PNBCs by Western Blot analysis (figure 1). We established expression profiles for PGRMC1 throughout the menstrual cycle (figure 2A). The levels of PGRMC1 were found stable across the menstrual cycle, with a tendency to peak in the preovulatory phase (though non-significant compared to any other cycle phase). Interestingly, there was no correlation between PGRMC1 levels and estradiol or progesterone variations. We next analyzed PGRMC1 levels in blood samples obtained from 6 patients with polycystic ovary syndrome (PCOS) and 8 patients with premature ovarian failure (POF). In addition, we included four healthy men and five healthy postmenopausal women as reference groups. The results from the PGRMC1 analyses in PCOS and POF patients, postmenopausal subjects and healthy males were compared to the PGRMC1 levels during the early follicular phase (eFP) of healthy women with ovulatory cycles in order to obtain comparable endocrine conditions. We observed a marked reduction in levels of PGRMC1 protein in the PCOS and POF groups in comparison to healthy cycling women in the early follicular phase (figure 2B). Furthermore, a similar reduction was observed among postmenopausal women as well as in healthy males when compared to healthy females in eFP (p-values < 0.01; figure 2B). The lowest PGRMC1 levels were observed in the group of postmenopausal women. The levels were significantly reduced when compared to healthy females and also when compared to healthy males (p-values < 0.05; figure 2B). POF patients displayed a broader range in PGRMC1 expression than PCOS patients, while PGRMC1 levels in PCOS patients fell between levels observed in postmenopausal controls and in males.


Down-regulation of progesterone receptor membrane component 1 (PGRMC1) in peripheral nucleated blood cells associated with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS).

Schuster J, Karlsson T, Karlström PO, Poromaa IS, Dahl N - Reprod. Biol. Endocrinol. (2010)

Detection of PGRMC1 and β-actin by Western blot analysis in total protein preparations obtained from peripheral nucleated blood cells (PNBC). Representative western blot pictures illustrating detection in (A) healthy cycling women (HF; distinct phases are indicated above), (B-D) PCOS and POF patients and control groups (PM, natural menopausal women; HM, healthy men). Total protein preparations were separated on a 12% SDS-PAGE, transferred to a PVDF membrane and subsequently detected using α-PGRMC1 and α-β-actin antibodies. A protein standard was included and the band sizes are indicated to the left. Bands corresponding to PGRMC1 (green) and β-actin (red) are indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2902486&req=5

Figure 1: Detection of PGRMC1 and β-actin by Western blot analysis in total protein preparations obtained from peripheral nucleated blood cells (PNBC). Representative western blot pictures illustrating detection in (A) healthy cycling women (HF; distinct phases are indicated above), (B-D) PCOS and POF patients and control groups (PM, natural menopausal women; HM, healthy men). Total protein preparations were separated on a 12% SDS-PAGE, transferred to a PVDF membrane and subsequently detected using α-PGRMC1 and α-β-actin antibodies. A protein standard was included and the band sizes are indicated to the left. Bands corresponding to PGRMC1 (green) and β-actin (red) are indicated.
Mentions: We obtained eight venous EDTA blood samples from each of 15 healthy women during four weeks. The time spans approximately one menstrual cycle and none of the women were on any hormonal treatment. Serum estrogen and progesterone levels were measured in each sample. Both hormones showed expected and normal profiles over the four weeks period (table 1). The hormone profile, LH surge and first day of menstrual bleeding were used to assign every sample to a distinct day of a standardized 28 day menstrual cycle (table 1). Subsequently, we analyzed PGRMC1 protein levels in total protein preparations derived from PNBCs by Western Blot analysis (figure 1). We established expression profiles for PGRMC1 throughout the menstrual cycle (figure 2A). The levels of PGRMC1 were found stable across the menstrual cycle, with a tendency to peak in the preovulatory phase (though non-significant compared to any other cycle phase). Interestingly, there was no correlation between PGRMC1 levels and estradiol or progesterone variations. We next analyzed PGRMC1 levels in blood samples obtained from 6 patients with polycystic ovary syndrome (PCOS) and 8 patients with premature ovarian failure (POF). In addition, we included four healthy men and five healthy postmenopausal women as reference groups. The results from the PGRMC1 analyses in PCOS and POF patients, postmenopausal subjects and healthy males were compared to the PGRMC1 levels during the early follicular phase (eFP) of healthy women with ovulatory cycles in order to obtain comparable endocrine conditions. We observed a marked reduction in levels of PGRMC1 protein in the PCOS and POF groups in comparison to healthy cycling women in the early follicular phase (figure 2B). Furthermore, a similar reduction was observed among postmenopausal women as well as in healthy males when compared to healthy females in eFP (p-values < 0.01; figure 2B). The lowest PGRMC1 levels were observed in the group of postmenopausal women. The levels were significantly reduced when compared to healthy females and also when compared to healthy males (p-values < 0.05; figure 2B). POF patients displayed a broader range in PGRMC1 expression than PCOS patients, while PGRMC1 levels in PCOS patients fell between levels observed in postmenopausal controls and in males.

Bottom Line: The levels of PGRMC1 protein in nucleated peripheral blood cells were quantified by Western blot analysis.PGRMC1 levels did not vary significantly throughout the menstrual cycle.We observed a significant down-regulation of PGRMC1 in postmenopausal women and in patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) when compared to early follicular phase of healthy women.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden. jens.schuster@genpat.uu.se

ABSTRACT

Background: Progesterone receptor membrane component 1 (PGRMC1) is a member of a progesterone-binding complex implicated in female reproduction. We aimed i) to determine the natural expression of PGRMC1 in peripheral nucleated blood cells throughout the menstrual cycle and ii) to investigate any association between PGRMC1 levels in leukocytes and conditions characterized by reduced fertility.

Methods: We analyzed PGRMC1 expression in peripheral leukocytes from 15 healthy cycling women over four weeks. Additionally, we determined PGRMC1 levels in samples from patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) as well as in healthy postmenopausal women and male controls. The levels of PGRMC1 protein in nucleated peripheral blood cells were quantified by Western blot analysis.

Results: PGRMC1 levels did not vary significantly throughout the menstrual cycle. We observed a significant down-regulation of PGRMC1 in postmenopausal women and in patients with premature ovarian failure (POF) and polycystic ovary syndrome (PCOS) when compared to early follicular phase of healthy women.

Conclusion: This study suggests that reduced levels of PGRMC1 in peripheral leukocytes are associated with perturbed ovulatory function.

Show MeSH
Related in: MedlinePlus