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Published on: September 18, 2017
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.
Abstract:
Offspring of rats with diabetes mellitus are at risk of reduced calcium and bone mineral content. Altered expression of the maternal calcium binding proteins, calbindin-D(9K) and calbindin-D(28K), which are involved in renal and placental calcium transport, may underlie these problems.We have investigated the effect of diabetes on circulating concentrations of regulatory hormones with respect to calbindin-D mRNA concentrations. Three rat groups were studied; control (CP), streptozotocin-induced diabetic (DP), and insulin-treated diabetic (DPI) pregnant rats. Calbindin-D(9K) and calbindin-D(28K) mRNA abundance in placenta and maternal kidney were measured at days 7, 15, 18 and 21 of gestation, together with serum or plasma concentrations of 1,25 dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)), parathyroid hormone (PTH), PTH-related protein (PTHrP), calcitonin, oestradiol and IGF-I. An increase in placental calbindin-D(9K) mRNA abundance between days 18 and 21 in CP and DPI rats was severely blunted in the DP rats. In contrast, renal calbindin-D(28K) mRNA abundance was greater at days 7, 15 and 18 in DP compared with CP rats, as was calbindin-D(9K) at day 18. Calcitonin concentrations showed no differences between the groups, and both PTH and IGF-I were reduced over the first half of gestation, unlike the calbindins. In contrast, the concentrations of PTHrP and 1,25(OH)(2)D(3) were reduced at term in the DP group compared with the other two groups. Plasma oestradiol concentrations were lower in DP than in CP rats at days 7, 15 and 18, and most striking was the absence in DP rats of the peak of oestradiol seen at day 18 in CP rats. Despite the similarity between changes in placental calbindin mRNA and 1,25(OH)(2)D(3), previous work has shown placental calbindin-D(9K) regulation to be vitamin-D-independent. These studies produce suggestive evidence, therefore, that PTHrP and oestradiol may be involved in the altered calbindin-D expression by kidney and placenta in rat diabetic pregnancy.

