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Biomedical subjects

E Roti

Publications and source records attributed to E Roti.

At least 91 records · Page 5Linked to original sources

Effect of pharmacological doses of oxytocin on insulin response to glucose in normal man.

In this study we have examined the effect of the administration of oxytocin on basal blood concentrations of insulin, glucagon, cortisol, growth hormone, and on the dynamic secretory response of these hormones to intravenous glucose administration (0.33 g/kg) in basal condition and after the injection of 3 IU (1 plus 2 IU/1 h) or 6 IU (2 plus 4 IU/1 h) of oxytocin (6 subjects for each group). The highest dose of oxytocin (6 IU) used significantly increased insulin secretion in response to intravenously administered glucose. No significant change of insulin secretion was observed with 3 IU of oxytocin. Glucagon, cortisol, and growth hormone response to intravenous injection of glucose was not affected by oxytocin (3 or 6 IU) administration. These results suggest that high doses of oxytocin affect beta-cell function in normal man.

Adult↗

The effects of propylthiouracil, iodothyronines, and other agents on thyroid hormone metabolism in human placenta.

Human and rat placental homogenates contain inner ring deiodinase activity (PT4ase) towards T4 and T3. This activity may decrease the transfer of T4 and T3 across the placenta and influence thyroid hormone disposal in the fetal circulation. Data are now presented on human PT4ase in subcellular fractions, the Km of human PT4ase, and the effects of drugs and other compounds on human and rat PT4ase. The specific activity (nanograms of rT3 produced per min/mg protein) of each fraction of human placenta was as follows: nuclear, 0.07; mitochondrial, 0.15; lysosomal, 0.19; microsomal, 1.30; and cytosol, 0.01. The apparent Michaelis-Menton (Km) for PT4ase in human placental microsomes was 1.2 X 10(-7) M. T3, 3,3'-diiodothyronine, iopanoic acid, iodoacetic acid, diamide, and propranolol all exhibited dose-dependent inhibition of human and rat PT4ase when tested in the presence of 10 mM dithiothreitol (DTT). Propylthiouracil did not inhibit PT4ase at 10 mM DTT, but when the DTT concentration was lowered to 0.25 mM, up to 71% inhibition was noted. Many drugs, as noted in other organs with respect to outer and inner ring iodothyronine deiodinases, inhibited human PT4ase. These studies may be relevant to the practice of administering propylthiouracil, propranolol, and iopanoic acid to pregnant women.

Animals↗

Inhibition of foetal growth hormone (GH) and thyrotrophin (TSH) secretion after maternal administration of somatostatin.

Somatostatin (SRIF) was infused (500 micrograms over 30 min) into 68 pregnant women during labour. As a control, saline was infused into 26 pregnant women. Maternal blood was obtained prior to the infusion and at delivery and cord blood was obtained at delivery. The subjects were divided into 4 groups based upon the interval of time from the termination of SRIF infusion and delivery. There was a marked decrease in cord blood thyrotrophin (TSH) from 0 to 180 min and in cord blood growth hormone (GH) from 0 to 120 min following SRIF infusion. SRIF infusion did not affect cord blood iodothyronine and thyroglobulin concentrations. SRIF administration induced a small but significant (P less than 0.05) decrease in serum GH concentration but had no other effect on maternal hormone values. These studies strongly suggest that SRIF crosses the human placenta and transiently suppresses foetal anterior pituitary TSH and GH secretion.

Blood Glucose↗

Inner ring deiodination of thyroxine and 3,5,3'-triiodothyronine by human fetal membranes.

Indirect evidence, based on injection of thyroxine (T4) into the amniotic cavity of humans, and maternal thyroidectomy in the rat, suggests that fetal membranes might be capable of converting T4 to 3,3',5'-triiodothyronine (rT3) by virtue of inner ring iodothyronine deiodinase activity. The present study was undertaken to provide direct evidence that human fetal membranes contain inner ring iodothyronine deiodinase activity directed toward T4 and 3,5,3'-triiodothyronine (T3). Homogenates of human fetal membranes were incubated with 125I-labeled T4, rT3, and T3, and with stable T4. Conversion of 125[I]-T4 to 125[I]-rT3 was noted in chorion and amnion. 125I-T3 was converted to 125[I]-3,3'-diiodothyronine (T2) in chorion and amnion. 125[I]-rT3 was stable in fetal membranes under the incubation conditions employed. Time-, temperature-, pH-, and protein content-dependent conversion of stable T4 to rT3 was found in fetal membranes. Iodothyronine metabolism did not occur in the absence of dithiothreitol. These studies indicate that human fetal membranes contain an inner ring deiodinase enzyme. Because of its intimate contact with the amniotic cavity, this enzyme may generate a portion of the rT3 found in amniotic fluid.

Amnion↗

Naloxone does not alter the effect of gamma aminobutyric acid derivative, baclofen, on GH release in man.

To evaluate the interaction between opioid peptides and GABAergic system in regulating GH secretion we administered 5 mg of baclofen, a GABA derivative, to eight normal male subjects. The results were compared to those obtained in the same subjects treated with naloxone (10 mg/2 h) plus baclofen. GH levels increased significantly above basal value either after baclofen and naloxone plus baclofen without any significant difference between GH responses during the two tests. It is suggested that the two substances do not act at the level of the same receptor site. The evaluation of a possible interaction between opioid peptides and GABAergic system on GH release requires further investigation.

Adult↗

Effect of metoclopramide on maternal and fetal hyperprolactinemia.

To investigate the effect of metoclopramide (MET), a dopaminergic antagonist drug, on serum PRL concentration in maternal and cord blood (CB) serum, the drug was injected in 94 at term pregnant women whereas 28 mothers received saline. Maternal serum (MS) samples were obtained before MET injection and at the parturition time. According to the interval of time between MET administration and birth, MS specimens were grouped in 7 groups. CB was obtained from neonates whose mothers were injected with saline, group 0 and from newborns whose mothers were treated with MET, groups 1 to 7. In the 7 groups of women the mean PRL concentration before MET ranged between 307 and 439 ng/ml. After MET injection a significant increase has been observed in all groups with a minimum and maximal mean value of 639 and 931 ng/ml. The highest net increment of PRL has been measured in group 1 sampled at 5 to 30 minutes after MET. CB PRL concentration in group 0, saline treated, was not different from the values measured in group 1 to 7, treated groups, with a range between 504 and 703 ng/ml. These findings suggest that maternal lactotropes are still responsive to MET. On the opposite, fetal pituitary does not release PRL after MET injection probably because PRL secretory activity is maximal or because the dopaminergic receptors' system is still immature.

Female↗

Failure of metoclopramide to affect thyrotropin concentration in the term human fetus.

Metoclopramide (MET), a potent dopamine receptor-blocking drug, or saline was administered to 125 term pregnant women at various time intervals (5-412 min) before delivery. Maternal serum was obtained before and after MET injection. Cord blood was obtained at delivery in MET-treated and saline-treated (control group) women. No significant changes in serum TSH, T4, T3, or rT3 concentrations were observed in maternal or cord blood after MET administration. These results suggest that, in contrast to euthyroid nonpregnant women and men, MET administration does not induce a rise in serum TSH concentration in term pregnant women or in the term fetus. Thus, the dopaminergic inhibitory effect on anterior pituitary TSH secretion may not be an important factor in TSH regulation during pregnancy or in the fetus, or the dose of MET employed may be unable to overcome the dopamine inhibitory effect.

Female↗

Rat placenta is an active site of inner ring deiodination of thyroxine and 3,3',5-triiodothyronine.

Inner ring deiodination of L-T4 and L-T3 by rat placental homogenates resulted in the generation of rT3 from T4 and 3,3'-diiodothyronine and 3'-monoiodothyronine from T3. Dithiothreitol is required in the incubation medium. There was little or no detectable outer ring deiodination of T4 and T3. These findings suggest that placenta enzymatic inner ring monodeiodination of T4 and T3 could prevent the transplacental passage of T4 and T3 from dam to fetus. They also provide an explanation for our previous observations that fetal serum rT3 is partially dependent on maternal thyroid function.

Animals↗

Ontogenesis of placental inner ring thyroxine deiodinase and amniotic fluid 3,3',5'-triiodothyronine concentration in the rat.

Human and rat placentae contain enzymatic activity which converts T4 to rT3 and T3 to 3,3'-diiodothyronine and 3'-monoiodothyronine. This study presents data on the ontogeny of this inner ring iodothyronine deiodinase activity (P-T4ase) in rat placenta. P-T4ase was measured by quantitating the conversion of T4 to rT3 in 700 x g supernatants of placental homogenates. Groups of rats were mated to permit the dams to be killed on the same day, on days 12, 14, 16, 18, and 20 of gestation. Sufficient placental tissue was obtained to measure P-T4ase on all but the 12th day of gestation. The highest level of P-T4ase was observed on day 16. P-T4ase on days 14, 18, and 20 was 52%, 77%, and 41%, respectively, of that observed on day 16 (P less than 0.01, day 16 vs. all other days). Amniotic fluid rT3 concentrations were highest on day 18 and were 61% and 64%, respectively, of that observed on day 18 (P less than 0.01, days 16 and 20 vs, day 18). At 20 days, maternal serum T4 concentrations were significantly lower (P less than 0.01) than on days 14, 16, or 18. A brief period of maternal hypothyroidism (4 or 9 days before the time that the animals were killed on day 20 of gestation) did not significantly alter P-T4ase. These studies indicate that there are age-dependent changes in placental inner ring deiodinase activity in the rat. Amniotic fluid rT3 concentrations may reflect these changes. Brief reductions in maternal serum T4 concentrations do not account for changes in placental inner ring deiodinase activity. These studies emphasize the importance of gestational age in studies of placental inner ring iodothyronine deiodinase.

Amniotic Fluid↗

Response of growth hormone to thyrotropin-releasing hormone during fetal life.

The effect of TRH administration to the term pregnant women on the GH response in cord blood (CB) was evaluated in 138 subjects. Previous studies have demonstrated that TRH readily crosses the placenta. TRH (400 microgram) was administered iv to 59 pregnant women just before delivery. CB samples were obtained at delivery and assigned to 6 groups, depending upon the duration of time between TRH injection and CB sampling. The control group comprised 79 pregnant women who received saline. A progressive rise and then a fall in the CB GH concentration were observed after TRH administration. Values were significantly elevated 61-90 min after TRH administration compared to values in saline-treated subjects (19.3 +/- 3.1 vs. 13.1 +/- 0.9 ng/ml; P less than 0.05). The present study is the first report of the effect of TRH on the GH concentration in CB and suggests that TRH stimulates GH release in the fetus.

Birth Weight↗

The sex-related difference in serum thyrotropin concentration is androgen mediated.

Studies were carried out on various aspects of hypothalamic-pituitary-thyroid function in normal and gonadectomized adult male and female rats. Consistent increases in the serum TSH concentration and the serum TSH response to TRH were observed in the male rat compared to values in the female. Orchiectomy induced a decrease in the serum TSH concentration and the serum TSH response to TRH, and these functions were equal in gonadectomized male and female rats. Oophorectomy did not affect basal and TRH-stimulated serum TSH concentrations. Replacement doses of testosterone (0.33 mg/day) to orchiectomized rats increased and restored these values to those observed in the normal male rat, while replacement doses of estradiol (0.33 microgram/day) to the oophorectomized rat had no effect on basal or TRH-stimulated TSH concentrations. No sex-related differences in pituitary TSH and hypothalamic TRH contents or in serum T4 and T3 concentrations were observed. The present studies strongly suggest that the increased TSH responsiveness observed in male compared to female rats is due to the presence of testosterone. (Endocrinology 108: 529, 1981)

Animals↗

Human placenta is an active site of thyroxine and 3,3'5-triiodothyronine tyrosyl ring deiodination.

Human placental homogenate deiodinates the tyrosyl ring of T4 and T3, converting these active thyroid hormones to the inactive iodothyronines, rT3 from T4, and 3,3'-diiodothyronine and 3'-monoiodothyronine from T3. The conversion of T4 or rT3 is time, temperature, pH, and protein content dependent and does not occur in the absence of the thiol-regenerating agent dithiothreitol. Phenolic ring deiodination of T4, T3, and rT3 was not detected. Failure of the transplacental passage of T4 and T3 from mother to fetus may be secondary to the placental tyrosyl ring deiodination of these iodothyronines.

Diiodothyronines↗

Human cord blood concentrations of thyrotropin, thyroglobulin, and iodothyronines after maternal administration of thyrotropin-releasing hormone.

TRH or saline was administered to 214 term pregnant women at various time intervals (8-820 min) before delivery. Cord blood (CB) was obtained, and plasma TSH, T4, T3, rT3, and thyroglobulin concentrations were measured by specific RIA. CB TSH was significantly elevated within 20 min after TRH administration and remained elevated for 180 min. CB T3 rose significantly by 60 min and remained elevated for 820 min. CB T4 was significantly increased from 120 to 820 min after TRH administration. There was no significant change in the CB thyroglobulin concentration. These findings demonstrate for the first time that TRH crosses the human placenta, that the fetal pituitary is responsive to TRH, and that endogenous TSH stimulates the fetal thyroid.

Female↗