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S P Porterfield

Publications and source records attributed to S P Porterfield.

15 recordsLinked to original sources
PubMed1992

Method for the quantitation of iodothyronines in body tissues and fluids using high-performance liquid chromatography.

The separation and quantitation of iodotyrosines and iodothyronines [3-monoiodo-L-tyrosine, 3,5-diiodo-L-tyrosine, 3,5-, 3,3' and 3',5'-diiodo-L-tyronines, 3,5,3'-triiodo-L-thyronine (T3), reverse 3,3',5'-triiodo-L-thyronine and 3,3',5,5'-tetraiodo-L-thyronine (T4)] from animal tissues (brain, liver and serum) by a new high-performance liquid chromatographic (HPLC) method is described. Rats were infused with iso-osmotic sodium chloride containing 100 microM phloretin to block deiodination. The tissues were extracted using differential pH values to separate other amines from the amine containing iodothyroid hormones. Aliquots of tissue extracts (25-100 microliters) were reacted overnight with 5-dimethylaminonaphthalene-1-sulfonyl chloride and their iodotyrosine and iodothyronine content determined by HPLC utilizing fluorimetric detection. Resolution of the individual compound peaks was achieved by gradient elution with a 3.0 mM H3PO4 buffer. Greater sensitivity has been achieved (less than 1.0 pmol/g) utilizing fluorescence rather than ultraviolet absorbance for the quantitation of these iodinated compounds. The method is superior also to other methods in that recoveries, based on those of 125I-labelled T4 and T3, were 89-97%.

Animals↗
PubMed1992

Tissue iodothyronine levels in fetuses of control and hypothyroid rats at 13 and 16 days gestation.

Some investigators have reported that there is minimal placental transport of thyroid hormones in humans and rats. Consequently, it was thought that thyroid hormones were not present in the fetal brain before fetal thyroid hormone synthesis and, hence, were not important for brain development before fetal thyroid hormonogenesis. Recently, however, thyroid hormones have been detected by 14 days postconception (dpc) in the rat fetus and by 11 dpc in the rat embryotrophoblast. Thyroid hormone receptors have been shown in the fetal rat by 14 dpc. The present experiments were designed to determine if T4, T3, and their metabolites can be detected in rat fetuses at 13 and 16 dpc and if iodothyronines are selectively accumulated in fetal brain and liver. Furthermore, one group of dams was radiothyroidectomized before breeding to ascertain the effect of maternal hypothyroxinemia on fetal tissue iodothyronine concentrations. Tissue iodothyronines were extracted and measured by HPLC. T4, T3, rT3, and 3,5-diiodothyronine were well within the limits of detection by this procedure at both fetal ages. The only possible source of these hormones is the mother. In addition, if maternal serum T4 levels are low, fetal tissue T4 and T3 levels are low. The presence of high intracellular T3 levels, even at 13 dpc, shows that 5'-monodeiodination occurs in the midgestational fetus. Intracellular hormone measurements show that T3, rather than rT3, is the predominant intracellular iodothyronine in the rat fetus. Both brain and liver selectively accumulate T4 and T3, supporting the observations of others that fetal thyroid hormone receptors are present in midgestation. The presence of thyroid hormones in fetal rat brain by 13 dpc coupled with the observation that hormone receptors are present by 14 dpc suggests that thyroid hormones do play a role in midgestational brain development. These data show that normal maternal serum thyroid hormone levels are important during midgestation to provide adequate thyroid hormones to the fetus.

Animals↗
PubMed1992

Serum growth hormone levels in hypothyroid and GH-treated thyroidectomized rats and their progenies.

Growth hormone (GH) was measured in the sera of control, hypothyroid (thyroidectomized [Tx]) and GH-treated Tx rats and their fetuses on Days 19, 20, 21, and 22 of gestation and in their progenies on postnatal Days 1, 5, 30, and 75. Maternal endogenous serum GH increased dramatically between the 19th and 20th days of gestation and remained elevated through the 22nd day in control rats, but was depressed significantly in Tx and GH-treated Tx rats during this period. GH was not always detected in the sera of 19-day-old fetuses. On Day 20, GH was depressed in fetuses of Tx mothers as compared with those form controls or GH-treated Tx mothers. GH was elevated in sera of fetuses from GH-treated Tx rats over fetuses of control and Tx only rats on the 22nd day of gestation. In postnatal rats, those from GH-treated mothers continued to show elevated serum GH on Day 1 as compared with those from Tx only mothers. On postnatal Days 5 and 30, progenies of Tx mothers had significantly elevated GH as compared with progenies of control mothers. At 75 days of age, the GH levels of these progenies had normalized. We have shown previously that the hormonal secretions of the pituitary-thyroid axis are badly disrupted in the progenies of Tx and GH-treated Tx mothers and that even as adults these animals have tissue (brain and liver) deficits of active thyroid hormones. Although the onset of GH secretion is mildly delayed in fetuses of Tx but not GH-treated Tx mothers, the serum GH levels of both groups of progenies are elevated during most of the neonatal period through the time of puberty. It is, therefore, concluded that GH in the absence of adequate levels of thyroid hormones is ineffective in preventing many of the learning and memory deficits induced in the progenies of Tx mothers.

Animals↗
PubMed1990

Distribution of free amino acids in streptozotocin-induced diabetic pregnant rats, their placentae and fetuses.

Amino acid levels in the non-pregnant streptozotocin (STZ)-induced diabetic rat have been shown to be abnormal. Our preliminary studies showed that placental transport, fetal serum levels and tissue uptake of the non-metabolizable amino acid alpha-amino isobutyric acid (AIB) were decreased in STZ-diabetic pregnant rats. In the present experiments, amino acid concentrations were measured in maternal (MS) and fetal (FS) sera and placentae (PL) by high performance liquid chromatography (HPLC) after triple extraction in 80% ethanol. Control (C), STZ-diabetic (D) and insulin-treated diabetic (DI) animals were studied at 22 days gestation. Pregnant diabetic rats had low serum levels of Gln, Lys, and Ser and insulin treatment corrected Gln and Ser but not Lys levels. Branched-chain amino acids did not show the large elevation characteristic of the non-pregnant diabetic rat. Placental levels of Tau, Gln, HPr, Thr and Lys were depressed in the diabetic animals and insulin treatment only partially improved these amino acid profiles. Placental amino acid levels did not always reflect maternal serum levels. Serum levels of most amino acids were lower in the fetus of the diabetic rat than in the fetus of the control rat. The notable exception was Ala which was higher in the fetuses of the diabetic animals. Insulin treatment of the mother did not correct many of the fetal amino acid levels even though maternal and fetal serum glucose levels at the time of autopsy were normal. The ability to maintain normal serum levels of many amino acids is impaired in the fetus of the diabetic rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1987

Effects of streptozotocin-induced diabetes in pregnant rats on placental transport and tissue uptake of alpha-amino-isobutyric acid.

Placental transport and tissue uptake of amino acids were studied in streptozotocin (STZ)-induced diabetic rats by using the non-metabolizable amino acid [U-14C]-alpha-amino-isobutyric acid (AIB). Fifteen minutes prior to autopsy, animals of each group, control (C), diabetic (D), diabetic-insulin treated (DI) and diabetic-T4 followed by 3-5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT) treated (DTD), received an injection of the [U-14C]-AIB SC. Disintegrations per minute (DPM) were measured in serum and tissues subsequent to autopsy. There were no differences in maternal serum DPM/ml among groups. Fetal serum DPM, however, were lower in D and DTD groups than in the C group. The whole fetal tissue homogenate radioactivity was lower in the D, DTD, and DI groups than in the C group. In general, more AIB was taken up by fetal tissues of C than D animals. Maternal liver AIB uptake was reduced in D, DI, and DTD from C animals and net placental transport of AIB was less in D and DTD than C animals. Fetal liver protein concentrations were depressed in D and DTD animals from C and DI, but fetal brain protein concentrations showed no significant differences. Furthermore, the lower organ and fetal body weights of the D and DTD groups compared with the C and DI groups support the proposal that fetal anabolism is impaired. Maternal and fetal serum T4 concentrations were lower in D and DTD than in C and DI animals. Insulin therapy improved serum T4 levels in both mother and fetuses. It did not, however, correct all other measured parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoisobutyric Acids↗
PubMed1987

Iodothyronine-5'-deiodinase activity in progenies of hypothyroid rats.

Iodothyronine-5'-deiodinase activity (I-5'DA) was measured in the progenies of control rats, hypothyroid (Tx) rats, and hypothyroid treated with ovine GH (Tx + GH) during gestation. The enzyme was measured in cerebral cortex and cerebellum at 22 days gestation and at 5, 10, 30 and 60 days postpartum. In addition, the pituitary I-5'-DA was assessed in the postnatal animals. The experiments were undertaken because the tissues of the progenies of rats that were hypothyroid during pregnancy appeared in many ways to resemble those of hypothyroid animals, even at ages when serum thyroxine (T4) and triiodothyronine (T3) levels were normal. It was found that the progenies of Tx mothers had low liver 5'-deiodinase activities. This is a likely cause of the low serum T3 levels with normal T4 levels seen in these progenies in the neonatal period. Cerebral and cerebellar 5'-deiodinase activities were low in these progenies during the thyroid hormone-dependent perinated period of brain development. The progenies of GH-treated Tx dams had higher enzyme activities than the progenies of untreated Tx dams. These pups from GH-treated Tx mothers have been shown previously to have significantly less neurological impairment than the progenies of untreated Tx mothers. As most of the brain intracellular T3 is produced in situ, a functional thyroid deficiency could result from such a 5'-deiodinase deficiency. As the deiodinase deficiency was still seen in the progenies of Tx mothers at 60 days of age, such a deficiency could explain why, even though serum T4 and T3 levels were normal, brain metabolism was in many ways characteristic of hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Prenatal exposure of the fetal rat to excessive L-thyroxine or 3,5-dimethyl-3'-isopropyl-thyronine produces persistent changes in the thyroid control system.

Studies were conducted to determine if brief exposure, in utero, to high levels of T4 or to the synthetic thyromimetic agent 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) can produce permanent disruption of the thyroid control system in a manner analogous to the changes in the "set point" reported to occur due to neonatal T4 exposure in the "neo-T4 syndrome". If such a change were to occur, it could explain the persistent thyroid disturbances seen in the progeny of hypothyroid mother rats. These latter progeny are exposed in utero to both low and high serum T4 levels. Maternal T4 treatment produced a 4-fold elevation in fetal serum T4 accompanied by a large decrease in serum TSH levels. The brief treatment in utero with high doses of T4 or of DIMIT resulted in higher neonatal mortality and the T4-treatment produce subsequent growth stunting. These treatments resulted in suppression of the fetal/neonatal thyroid which was very apparent at 5 days of age. At 30 days post-partum, the thyroid control system of the progeny of the T4 and DIMIT-treated animals was still abnormal with low serum T4 levels accompanied with normal serum TSH and T3 levels. At 60 days of age, serum T4 levels remained low in the progeny of the T4-treated animals and the TSH response to TRH was subnormal in both the progeny of the T4-treated and the DIMIT-treated animals. However, serum and pituitary TSH and serum T3 were normal. The thyroid control system of the rat is sensitive to prenatal exposure to hyperthyroxinemia as it is to postnatal exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Pituitary-thyroid function of fetuses of hypothyroid and growth hormone treated hypothyroid rats.

Maternal hypothyroidism induced by surgical thyroidectomy (Tx) of the rat resulted in significantly higher fetal serum levels of thyroid stimulating hormone (TSH) and thyroxine (T4) on day 22 of gestation. Surprisingly, administration of growth hormone (GH) to hypothyroid mothers increased further the fetal serum T4 and TSH. The in vitro uptake of 131I-T4 by erythrocytes was elevated significantly when incubated with serum from fetuses of both hypothyroid and hypothyroid GH-treated mothers. Although the plasma protein levels of hypothyroid mothers and their fetuses are decreased significantly as compared to controls this is not true of hypothyroid GH-treated mothers and their fetuses. The T4 levels of both groups of Tx mothers were significantly below that of controls. However, as in the case of their fetuses, the serum T4 of GH-treated hypothyroid mothers was elevated from that of Tx only animals. It is concluded that the pituitary-thyroid system of fetuses of hypothyroid mothers is activated excessively during late gestation, that considerable T4 can be transported from the fetus to the mother during this period and that these fetuses are in fact born in a hyperthyroid state which is aggravated by maternal treatment with GH.

Animals↗
PubMed1979

The effects of growth hormone, thyroxine and insulin on the activities of reduced nicotinamide adenine dinucleotide phosphate dehydrogenase, glucose-6-phosphatase and glycogen phosphorylase in fetal rat liver.

Growth hormone (GH), thyroxine (T4) and insulin were injected, in utero into 20.5 day-old rat fetuses to study the effects of these hormones on the activities of liver NADPH dehydrogenase, glucose-6-phosphatase and glycogen phosphorylase. It was found that at 21.5 days of gestation, GH increases the fetal liver glucose-6-phosphatase activity and decreases the liver glycogen phosphorylase activity. T4 treatment augments the activity of NADPH dehydrogenase even at 0.3% of the dose shown previously to produce premature elevation of activity. Prior to this experiment T4 in large doses has been shown to be capable of elevating glucose-6-phosphatase. However, at the lower T4 dose used, no treatment effect was observed. The fetal rat liver is responsive to insulin at 21.5 days and insulin was able to depress glucose-6-phosphatase activity. Thereby, showing that the influence of insulin on this enzyme begins prior to birth instead of just subsequent to birth.

Animals↗
PubMed1976

A comparison of the effects of altered thyroid and parathyroid function on reproduction in the rat.

Mild maternal hypothyroidism produced by surgical thyroidectomy resulted in significantly reduced food intake along with retarded reproductive performance in rats. Hyperthyroidism increased food consumption above the control level along with an increase in fetal resorptions which was the only parameter of reproductive performance altered by the twenty-second day of gestation. In animals which underwent pregnancies, reproductive performance suffered a further decline in the second gestation due to increasing duration of the hypothyroidism. Food restriction alone failed to duplicate these adverse effects on fetal development. Serum gonadotropins (LH and FSH) were not significantly altered by mild maternal hypothyroidism of hypoparathyroidism. The hematocrit and total blood volume of hypothyroid but not hypoparathyroid rats was significantly reduced from normal. Maternal hypoparathyroidism alone did not affect fetal development grossly.

Animals↗
PubMed1976

The effects of growth hormone treatment of thyroid-deficient pregnant rats on maternal and fetal carbohydrate metabolism.

Maternal hypothyroidism in rats has been shown previously to result in alterations of maternal, placental, and fetal metabolism. Maternal treatment with 2 IU GH/day for three days prior to autopsy (on the 22nd day of pregnancy) corrected many of the observed alterations of carbohydrate metabolism in hypothyroidism. The maternal and fetal liver glycogen concentrations and the fetal serum glucose levels of the hypothyroid animals were elevated significantly by the GH treatment. In most cases, the utilization of a [1-14C]glucose tracer dose was returned to normal by GH treatment. These results suggest that the impairment of fetal metabolism occurring in maternal hypothyroidism may be due in part to insufficient maternal GH secretion. However, GH alone in the absence of sufficient thyroid hormones did not totally correct all of the observed fetal abnormalities.

Animals↗
PubMed1975

The effect of maternal hypothyroidism on maternal and fetal tissue glucose-1-14C incorporation in rats.

These experiments were conducted to help elucidate the mechanism for the impaired fetal development occurring during maternal hypothyroidism. The disposition of glucose was measured using glucose-1-14C. Maternal hypothyroidism depressed glucose utilization in thematernal-fetal system. Maternal net glycogen synthesis from the labeled glucose was impaired. However, while the fetal glycogen storage system may be capable of at least relatively normal glycogen synthesis, abnormally low levels of glycogen were measured. If, as the data suggest, enzymatic deficiencies do not exist, the low liver glycogen might be a result of the inability of the maternal-placental system to provide adequate substrate to the fetus.

Animals↗
PubMed1975

Hypoglycemia and glycogen deficits in fetuses of hypothyroid pregnant rats.

Maternal hypothyroidism, when induced by surgical thyroidectomy with parathyroid hormone replacement, results in fewer live fetuses and smaller fetuses at the 22nd day of gestation. The hypothyroid mother shows the ability to mobilize adequate amounts of glucose even at the expense of her own reserves but the supply of glucose to the fetus appears to be impaired. These fetuses have subnormal skeletal muscle and liver glycogen and are severely hypoglycemic. The impaired development of these fetuses may result from alterations of either transplacental carbohydrate transport or placentofetal carbohydrate metabolism.

Animals↗