Variation in glucocorticoid receptor isoform expression and location in the human placenta: A possible mechanism that confers a sex specific difference in the response to glucocorticoids — ASN Events
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  3. Variation in glucocorticoid receptor isoform expression and location in the human placenta: A possible mechanism that confers a sex specific difference in the response to glucocorticoids

Variation in glucocorticoid receptor isoform expression and location in the human placenta: A possible mechanism that confers a sex specific difference in the response to glucocorticoids (#306)

Zarqa Saif 1 , Nicolette Hodyl 2 , Eleanor Hobbs 2 , Peter Fuller 3 , Timothy Cole 4 , Vicki Clifton 5
  1. Robinson Institute, University of Adelaide, Elizabeth vale, SA, Australia
  2. Robinson Institute, The university of Adelaide, Adelaide, SA, Australia
  3. Steroid Receptor Biology, Prince Henry Institute, Melbourne, VIC, Australia
  4. Biochemistry and molecular biology, Monash university, Melbourne, VIC, Australia
  5. Robinsin Institute, University of Adelaide , Elizabeth vale, SA, Australia

Background: We have observed sex specific differences in the fetal-placental response to glucocorticoids (GC). In the presence of maternal asthma, the female placentae remain sensitive to glucocorticoids, while male placentae appear to induce a state of glucocorticoid resistance when exposed to excess cortisol. Our recent findings have identified that the differential response to increased cortisol is mediated by differences in glucocorticoid receptor (GR) bioactivity. However the exact mechanism is unknown.
Objectives: We are interested in determining whether glucocorticoid sensitivity or resistance is conferred by the differential expression of known GR isoforms including GRβ, GRγ, GR-P, GR-A, GRα-A, GRα-B1-2, GRα-C1-3 and GRα-D1-3 as well as the phosphorylation status of GRα in placenta.
Methods: Cytosolic and nuclear protein fractions of placentae were analysed by Western blot to examine GR protein expression, phosphorylation and location in placental tissues from normal and asthmatic pregnancies.
Results: We have identified 12 GR specific bands differentially located in nuclear and cytosolic fractions of the human placenta that vary in relation to fetal sex and maternal asthma. These include some known isoforms at molecular weights corresponding to GRα (94kDa), GRβ (91kDa), GRα-C1-3 (81kDa), GR-P (74kDa), GR-A (65kDa) and GRα-D1-3 (45-50kDa). Some isoforms detected in this study are not previously reported, including bands at 68-69kDa, 60kDa and 38kDa size. Male placentae had increased nuclear expression of GR A and P relative to female placentae. In the presence of maternal asthma there was increased nuclear expression of GRα and GRα-D3 in female and increased cytoplasmic GRβ expression in male placentae. There was a significant increase in GR-s226 phospho proteins in relation to maternal asthma but not in relation to fetal sex.
Conclusion: Sex specific differences in GR isoform expression and location may confer sensitivity to glucocorticoids with GRβ, GR A and GR P potentially driving glucocorticoid resistance in males.

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