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Effect of pregnancy, postnatal growth, and gender on renal sulfate transport
H J Lee1, S V Balasubramanian, M E Morris
1Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, Amherst, New York 14260, USA.
Insights
Serum sulfate levels are higher in young and pregnant individuals. Renal sulfate transport, specifically sodium/sulfate co-transport in the brush-border membrane (BBM), is elevated in young and pregnant guinea pigs, suggesting increased transporter activity.
Area of Science:
- Nephrology
- Biochemistry
- Physiology
Background:
- Serum sulfate concentrations are elevated in infants, children, and pregnant women compared to adults.
- Renal sulfate transport plays a crucial role in maintaining sulfate homeostasis.
Purpose of the Study:
- To investigate the impact of age, gender, and pregnancy on renal sulfate transport mechanisms in guinea pigs.
- To explore potential alterations in membrane fluidity contributing to observed transport changes.
Main Methods:
- Isolation of kidney cortex membrane vesicles (brush-border membrane - BBM, and basolateral membrane - BLM) from guinea pigs of varying ages, genders, and reproductive status.
- Measurement of Na+/sulfate co-transport kinetics (Vmax and Km) in BBM.
- Assessment of bicarbonate-driven sulfate exchange in BLM.
- Determination of membrane fluidity using fluorescence anisotropy.
Main Results:
- Na+/sulfate co-transport Vmax in BBM increased significantly with decreasing age and was higher in pregnant animals compared to non-pregnant ones.
- Renal BBM fluidity was elevated in younger and pregnant animals.
- No significant gender-related differences in sulfate transport were observed in adult animals.
- Bicarbonate/sulfate exchange in BLM showed no age-related differences, but Km was higher in pregnant animals.
Conclusions:
- Age and pregnancy significantly influence renal sodium/sulfate co-transport, likely mediated by increased BBM fluidity and/or transporter protein activity.
- These adaptations may support increased demand for sulfated substrates during growth and development.
- Renal sulfate handling is dynamically regulated in response to physiological states like growth and pregnancy.
Abstract:
Serum sulfate concentrations are increased in infants, young children, and pregnant women, compared with adult values. The objective of this investigation was to examine the influences of age, gender, and pregnancy on renal sulfate transport using guinea pigs as an animal model. Membrane vesicles were isolated from the kidney cortex of male animals at four different ages, from male and female adult animals, and from pregnant and nonpregnant female animals. There were no significant differences in marker enzymes for the brush-border membrane (BBM) or basolateral membrane (BLM) among all groups examined. Uptake was determined by a rapid filtration method and membrane fluidity by measuring the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene. The Vmax values for Na+ /sulfate co-transport in BBM were significantly increased with decreasing age, whereas the Km for this process was unchanged. The Vmax and Km for Na + /sulfate co-transport in BBM of pregnant animals were significantly higher than the values in the nonpregnant group. Bicarbonate-driven anion exchange of sulfate in BLM was not different among the different age groups. The Vmax for the bicarbonate/sulfate exchange process in BLM was not different between pregnant and nonpregnant groups; however, the Km for this process in BLM of pregnant animals was significantly greater than the value in nonpregnant animals. There were no gender-related differences in sulfate transport in BBM or BLM isolated from adult male and female animals. Renal BBM fluidity was increased with decreasing age and in pregnant animals, suggesting that altered membrane fluidity may represent one possible mechanism to explain the increased sodium/sulfate uptake in young and pregnant animals. The higher Vmax for Na+/sulfate co-transport in young and pregnant animals suggests that there is an increased density of co-transporter protein or an increase in the rate of movement of the carrier protein (i.e., turnover) once loaded with sodium and sulfate. This increased conservation of inorganic sulfate in young and pregnant guinea pigs may be related to the increased demand for sulfated substrates, such as sulfated glycosaminoglycans, during growth and development.