The osmotic water permeability (P f ) 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 (T 3 ; 10 g/100 g body weight) for three days before study. P f was found to be higher in BBMV from hypothyroid (82.7 Ϯ 5.5 m/s) than from euthyroid (60.6 Ϯ 4.0 m/s) and T 3 -replacement rabbits (69.0 Ϯ 5.0 m/s) (p Ͻ 0.05). The activation energy (E a ; in kcal/deg⅐mol) of P f was not different among the three experimental groups (euthyroid 5.6 Ϯ 0.9, hypothyroid 4.9 Ϯ 0.8, T 3 -replacement 5.0 Ϯ 1.0; p ϭ NS), nor was the percentage mercury inhibition of P f (euthyroid 66.5 Ϯ 5.3, hypothyroid 74.2 Ϯ 3.2 and T 3 -replacement 73.1 Ϯ 4.3; p ϭ NS). AQP1 expression, measured by immunoblotting, was highest in BBMV from hypothyroid rabbits (p Ͻ 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 Ϯ 0.004, hypothyroid 0.271 Ϯ 0.004 and T 3 -replacement 0.287 Ϯ 0.003; for all p Ͻ 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 P f when rabbits are studied as adults. The higher P f in hypothyroid adult rabbits is due to a higher expression of AQP1 protein as well as a greater membrane fluidity than in euthyroid rabbits. The proximal tubule reabsorbs approximately two-thirds of the glomerular ultrafiltrate (1). This occurs in a nearly isoosmotic manner due to the high water permeability of this segment. We have previously demonstrated that the osmotic water permeability of both apical (brush border) and basolateral membranes increased during postnatal development (2, 3). In both membranes, this was accompanied by an increase in aquaporin-1 (AQP1) expression; the predominant water channel in proximal tubular membranes (4).The factors that are responsible for the maturational change in proximal tubule water transport and AQP 1 expression remain unknown. Thyroid hormone levels rise postnatally (5, 6) and have been shown to be a factor in developmental changes in proximal tubular function, including NaCl transport (7), Na ϩ /H ϩ -antiporter activity (5) and phosphate transport (6). The role of thyroid hormone with regard to ...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.