Altered calbindin mRNA expression and calcium regulating hormones in rat diabetic pregnancy

K Hamilton1, M Tein, J Glazier

  • 1School of Biological Sciences, Academic Unit of Child Health, University of Manchester, Manchester M13 9PT, UK. Khamil@fs1.cmht.nwest.nhs.uk

Insights

Maternal diabetes in rats alters calcium-binding protein (calbindin-D) mRNA in kidneys and placentas, potentially affecting offspring bone health. Hormonal changes, particularly PTHrP and estradiol, may drive these calbindin-D expression alterations.

Area of Science:

  • Endocrinology
  • Developmental Biology
  • Mineral Metabolism

Background:

  • Maternal diabetes mellitus is linked to reduced calcium and bone mineral content in offspring.
  • Altered expression of maternal calcium-binding proteins (calbindin-D9K and calbindin-D28K) is implicated in renal and placental calcium transport issues.
  • These proteins are crucial for calcium homeostasis during pregnancy.

Purpose of the Study:

  • To investigate the impact of diabetes on maternal circulating hormones and calbindin-D mRNA concentrations during pregnancy.
  • To examine the relationship between diabetes, hormonal regulation, and calcium transport proteins in pregnant rats.
  • To identify potential hormonal factors influencing calbindin-D expression in diabetic pregnancy.

Main Methods:

  • Studied three groups of pregnant rats: control (CP), streptozotocin-induced diabetic (DP), and insulin-treated diabetic (DPI).
  • Measured calbindin-D9K and calbindin-D28K mRNA abundance in placenta and maternal kidney at key gestational days (7, 15, 18, 21).
  • Assessed serum/plasma concentrations of regulatory hormones including 1,25-dihydroxyvitamin D3, PTH, PTHrP, calcitonin, estradiol, and IGF-I.

Main Results:

  • Placental calbindin-D9K mRNA increase at term was blunted in diabetic rats.
  • Renal calbindin-D28K and calbindin-D9K mRNA abundance was elevated in diabetic rats during mid-gestation.
  • PTHrP and 1,25-dihydroxyvitamin D3 were reduced at term in diabetic rats, while estradiol levels showed a significant reduction, particularly the peak at day 18.

Conclusions:

  • Diabetic pregnancy in rats is associated with altered calbindin-D mRNA expression in the kidney and placenta.
  • Hormonal changes, specifically reduced PTHrP and estradiol, may play a significant role in these altered calbindin-D expressions.
  • These findings suggest potential mechanisms linking maternal diabetes to impaired calcium transport and offspring bone health.