title: Parathyroid hormone-related protein and glucocorticoid receptor beta are regulated by cortisol in the kidney of male mice.
abstract: OBJECTIVE
  Parathyroid hormone-related protein (PTHrP) is a peptide growth factor produced in a wide range of tissues from brain and parathyroid, to kidney and uterus. The purpose of this study was to determine whether the adrenal cortical hormones, hydrocortisone (cortisol), modulate PTHrP expression and glucocorticoid receptor (GR)β in mice kidney.
  
  
  METHODS
  Changes in PTHrP gene expression were determined by real-time PCR and its protein level was examined by Western blot analysis. In addition, expression of renal PTHrP protein was localized by immunohistochemistry. Effects of RU486 on the expression levels of GRα/β or PTHrP gene in the kidneys were analyzed by Western blot analysis.
  
  
  RESULTS
  We found that renal expression levels of PTHrP mRNA were higher in males than in females up to 9weeks of age. Using immunohistochemistry, we observed higher levels of PTHrP expression within the cortex than in the medulla in both male and female mice, and this expression was localized in the epithelial cells of the renal proximal tubules. Treatment of 4-week-old mice with aldosterone and cortisol for three days showed larger increases in both PTHrP mRNA and protein levels in males compared with females. The expression of GRβ in male, but not female, kidneys was significantly upregulated after treatment with cortisol, but not after treatment with aldosterone. Inhibition of glucocorticoid signaling by pre-treatment with a GR antagonist prior to cortisol administration largely abolished this cortisol-dependent increase in PTHrP and GRβ expressions.
  
  
  CONCLUSIONS
  These results suggest that PTHrP expression and GRβ in the kidneys of male mice may be regulated by cortisol.
authors.affiliation: Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Yoo
authors.forename: Myung-Gi
authors.initials: MG
authors.lastname: Baek
authors.forename: Eui-Man
authors.initials: EM
authors.lastname: Jung
authors.forename: Hyun
authors.initials: H
authors.lastname: Yang
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.forename: Frank H
authors.initials: FH
authors.lastname: Yu
authors.forename: Eui-Bae
authors.initials: EB
authors.lastname: Jeung
mesh_terms: D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D006854:Hydrocortisone / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D044162:Parathyroid Hormone-Related Protein / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012737:Sex Factors
chemical_list: D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C121943:glucocorticoid receptor beta; D000450:Aldosterone; D006854:Hydrocortisone