Biomedical subjects

E L Stanley

Publications and source records attributed to E L Stanley.

14 recordsLinked to original sources

PubMed2001

Thyroid hormone metabolism and the developing human lung.

Thyroid hormones are involved in the regulation of fetal lung development, and maturation is accelerated in animal models by antepartum exposure to raised concentrations of the receptor-active thyroid hormone triiodothyronine and glucocorticoids. It is essential that the nature of the regulation of the spatial and temporal metabolism of iodothyronines in the human fetus and infant is known before effective therapies can be developed to modify human lung maturation. Thyroid hormone bioavailability to the human fetus is regulated in part by enzymatic deiodination and reversible sulfation of iodothyronines, with contributions from other factors such as fetomaternal and fetoamniotic hormone transfers, fetal thyroid gland production, and the activities of plasma membrane transporters mediating uptake of iodothyronines from plasma into tissues.

Arylsulfatases↗

PubMed2001

Differential expression of sulfotransferase enzymes involved in thyroid hormone metabolism during human placental development.

Thyroid hormone is essential for normal human development, and disruption of thyroid hormone homeostasis at critical developmental stages can result in severe and often long-term effects on crucial organs such as the brain and lungs. Numerous factors control the bioavailability of receptor active thyroid hormone T(3). Sulfation, catalyzed by sulfotransferase enzymes (SULTs), is an important pathway of thyroid hormone metabolism by which T(4) is irreversibly converted to inactive reverse T(3) rather than active T(3). The human fetus and neonate have high levels of circulating sulfated iodothyronines, although the source of these is not clear. The placenta forms the link between the fetus and its mother and is involved in transfer of thyroid hormone early in pregnancy, although its capacity for sulfation is unknown. We therefore examined expression of the SULTs involved in iodothyronine metabolism during human placental development. SULT activity was measured in human placental cotyledon and membranes (amnion, chorion, and decidua basalis) from 13-42 wk of gestation, and Western blot analysis was employed to verify enzyme activity data. Phenol and catecholamine sulfotransferases were expressed at the highest levels and were generally higher in the villous than membranous tissues. SULT1A1 activity showed significant correlation with sulfation of 3,3'-T(2), suggesting that this enzyme is primarily responsible for placental T(2) sulfation. Estrogen sulfotransferase was present at extremely low levels during early pregnancy, although in mid- and late gestation increased expression in the (predominantly maternal-derived) decidual component of the placenta was observed. Hydroxysteroid sulfotransferase, T(3), reverse T(3), and T(4) SULT activities were also low in all tissues examined, and expression of SULTs 1B1 and 1C2 were essentially undetectable by Western blot analysis. The results highlight a tissue-specific regulation of SULT expression during placental development, demonstrate very low sulfation of iodothyronines suggesting that the placenta is not a major source of circulating sulfated iodothyronines in the fetus.

Female↗

PubMed2001

Sulfation of thyroid hormone and dopamine during human development: ontogeny of phenol sulfotransferases and arylsulfatase in liver, lung, and brain.

Sulfation is an important mechanism for regulating the biological activity of numerous hormones and neurotransmitters in man. Here we have investigated the ontogeny of sulfotransferases (SULT) and sulfatase (ARS) involved in the metabolism of thyroid hormone and dopamine. SULT1A1 enzyme activity was lower in postnatal liver and lung than in fetal tissues. Hepatic SULT1A3 (dopamine) was expressed at high levels early in development, but decreased substantially in late fetal/early neonatal liver and was essentially absent from the adult liver. In lung, significant SULT1A3 activity was observed in the fetus, but neonatal levels were considerably lower. In brain, the highest activity was observed in the choroid plexus for SULT1A1, with low and widespread activity for both SULT1A1 and SULT1A3 in other brain regions. SULT activity with 3,3'-diiodothyronine (3,3'-T(2)) as substrate was measured in all tissues and correlated significantly with SULT1A1 activity (4-nitrophenol), suggesting that SULT1A1 is primarily responsible for the sulfation of this iodothyronine. The developmental expression of SULT1A3 and SULT1A1 in liver and brain was confirmed by immunoblot, and immunohistochemistry of developing liver showed substantial expression of these proteins in hemopoietic cells in fetal liver. We also detected low activity for the hydrolysis of 3,3'-T(2) sulfate by ARS, although there was less distinction between fetal and neonatal samples than with SULT activities. We have therefore shown that the developing fetus has substantial sulfation capacity. Sulfation may therefore play a major role in the homeostasis of hormones and other endogenous compounds as well as in detoxification in the fetus, particularly as other conjugating enzyme systems, such as the UDP-glucuronosyltransferases, are not expressed at significant levels until the neonatal period.

Aging↗

PubMed1985

Mechanism of diuretic-induced hypopotassemia in human hypertension.

Diuretic treatment (hydrochlorothiazide) induced a marked decrease of red cell membrane Na+K+ ATPase activity in excessive potassium loser hypertensive patients. The decreased activity occurred within 2-4 weeks of treatment and returned to baseline in 4-6 weeks after cessation of treatment. Simultaneously, red cell sodium increased, potassium decreased together with increased 24-h urinary excretion. The persistent low serum potassium may be due to impaired absorption of potassium from the gut as a result of suppressed enzyme activity since total body potassium appears also to decrease. The decreased Na+K+ ATPase activity may be due to a direct effect of the diuretic on cell membrane.

Calcium↗

PubMed1978