Hypothyroidism increases osmotic water permeability (Pf) in the developing renal brush border membrane

Jaap Mulder, Maha Haddad, Kimberly Vernon, Michel Baum, Raymond Quigley

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The osmotic water permeability (Pf) of the rabbit proximal tubule brush border membrane vesicles (BBMV) increases during maturation and is mediated by an increase in aquaporin-1 (AQP1) protein expression. Serum thyroid hormone levels increase after birth and have been shown to play a role in the maturation of other renal transport functions. We examined the hypothesis that thyroid hormone plays a role in the maturational increase in osmotic water permeability. Hypothyroidism was induced by addition of 0.1% propylthiouracil (PTU) to the drinking water of pregnant rabbits (starting 9 d before delivery) and was continued until the rabbits were studied as adults (9-11 wk). Some animals received thyroid hormone replacement by daily injection with triiodothyronine (T3; 10 μg/100 g body weight) for three days before study. Pf was found to be higher in BBMV from hypothyroid (82.7 ± 5.5 μm/s) than from euthyroid (60.6 ± 4.0 μm/s) and T3-replacement rabbits (69.0 ± 5.0 μm/s) (p < 0.05). The activation energy (Ea; in kcal/deg·mol) of Pf was not different among the three experimental groups (euthyroid 5.6 ± 0.9, hypothyroid 4.9 ± 0.8, T3-replacement 5.0 ± 1.0; p = NS), nor was the percentage mercury inhibition of Pf (euthyroid 66.5 ± 5.3, hypothyroid 74.2 ± 3.2 and T3-replacement 73.1 ± 4.3; p = NS). AQP1 expression, measured by immunoblotting, was highest in BBMV from hypothyroid rabbits (p < 0.05). Membrane fluidity, measured as steady-state generalized polarization (GP) of Laurdan, which is inversely related to membrane fluidity, was significantly different between the three groups (GP: euthyroid 0.307 ± 0.004, hypothyroid 0.271 ± 0.004 and T3-replacement 0.287 ± 0.003; for all p < 0.05). These data demonstrate that the maturational increase in thyroid hormone levels is not responsible for the maturational increase in water transport. Surprisingly, congenital hypothyroidism in rabbits is associated with an increased Pf when rabbits are studied as adults. The higher Pf in hypothyroid adult rabbits is due to a higher expression of AQP1 protein as well as a greater membrane fluidity than in euthyroid rabbits.

Original languageEnglish (US)
Pages (from-to)1001-1007
Number of pages7
JournalPediatric Research
Volume53
Issue number6
DOIs
StatePublished - Jun 1 2003
Externally publishedYes

Fingerprint

Microvilli
Hypothyroidism
Permeability
Rabbits
Kidney
Membranes
Water
Aquaporin 1
Thyroid Hormones
Membrane Fluidity
Propylthiouracil
Congenital Hypothyroidism
Triiodothyronine
Mercury
Immunoblotting
Drinking Water
Body Weight
Parturition
Injections
Serum

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Hypothyroidism increases osmotic water permeability (Pf) in the developing renal brush border membrane. / Mulder, Jaap; Haddad, Maha; Vernon, Kimberly; Baum, Michel; Quigley, Raymond.

In: Pediatric Research, Vol. 53, No. 6, 01.06.2003, p. 1001-1007.

Research output: Contribution to journalArticle

Mulder, Jaap ; Haddad, Maha ; Vernon, Kimberly ; Baum, Michel ; Quigley, Raymond. / Hypothyroidism increases osmotic water permeability (Pf) in the developing renal brush border membrane. In: Pediatric Research. 2003 ; Vol. 53, No. 6. pp. 1001-1007.
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