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Abstract: FR-PO843

Sex Differences in Regional Distribution of Key Steroidogenic Enzymes in the Rat Kidney

Session Information

Category: Women's Health and Kidney Diseases

  • 2200 Women's Health and Kidney Diseases

Authors

  • Shelton, Leah B., Eastern Virginia Medical School, Norfolk, Virginia, United States
  • Nasci, Victoria L., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Singh, Ravneet, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Gohar, Eman Y., Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background

Extragonadal estrogen (E2) synthesis has been demonstrated in tissues such as brain, bone, and adipose tissue. We recently demonstrated preliminary evidence for an intrarenal E2 synthesis machinery in the outer medulla (OM) of Sprague Dawley rats. Measurement of renal E2 showed higher E2 levels in female inner medulla (IM) compared to male rats. Thus, we aimed to investigate regional sex differences in renal E2-synthesizing enzymes that impact sex differences in E2 abundance.

Methods

Kidneys from male and female Sprague Dawley rats (n=8/group) were flushed, dissected into cortex (CTX), OM, and IM regions, and assessed for mRNA expression or protein abundance of enzymes in the E2 biosynthesis pathway.

Results

mRNA expression of 3-hydroxy-3methylglutaryl CoA reductase (HMGCR), the key enzyme in cholesterol synthesis (the first substrate in steroidogenesis), was higher in female OM compared to males (100.0 ± 14.4 vs 254.4 ± 50.5 relative expression, p=0.0148), while no sex difference in HMGCR mRNA was observed in CTX or IM. Cytochrome P450 (CYP) 17a1, which synthesizes weak androgens, showed greater mRNA expression in female CTX and OM, while males expressed higher levels in IM (CTX: 100.0 ± 34.7 vs 204.0 ± 71.1, p=0.0120; OM: 100.0 ± 41.0 vs 228.9 ± 78.0, p=0.0017; IM: 100.0 ± 37.5 vs 36.3 ± 15.2, p=0.0010). We also assessed mRNA expression of 17b-hydroxysteroid dehydrogenase (HSD17b) 1, 2, and 3 which interconvert androgens and estrogens. HSD17b1 was higher in male CTX and OM (CTX: 100.0 ± 46.5 vs 7.6 ± 1.3, p=0.0003; OM: 100.0 ± 52.6 vs 10.1 ± 2.4, p=0.0005), while HSD17b2 and 3 were higher in female CTX and OM (CTX: 100.0 ± 43.8 vs : 454.8 ± 271.1, p=0.0042, 100.0 ± 49.9 vs 199.5 ± 119.8, p=0.0790, respectively; OM: 100.0 ± 40.5 vs 619.6 ± 311.8, p=0.0006, 100.0 ± 25.8 vs 164.8 ± 33.2, p=0.0011, respectively). Protein expression of aromatase (estrogen synthase) was detected in CTX, OM, and IM without sex differences.

Conclusion

Our data indicate sex- and region-specific differential expression of the intrarenal E2 biosynthesis pathway within the rat kidney. HMGCR, CYP17A1, and HSD17b2 and 3 were upregulated within the female rat renal CTX and/or OM, but not IM, compared to males. Region-specific upregulation of these enzymes in females may contribute to renoprotective effects.

Funding

  • Other NIH Support