PubMed Health⌕ Search

Biomedical subjects

S W Spaulding

Publications and source records attributed to S W Spaulding.

At least 55 records · Page 3Linked to original sources
PubMed1980

Increased 17 beta-hydroxysteroid dehydrogenase activity in a masculinizing adrenal adenoma in a patient with isolated testosterone overproduction.

The patient studied had noted the onset of virilization shortly after menopause. Urinary 17-ketosteroid levels were normal, as were fractionated 17-ketosteroid levels by gas liquid chromatography, but for 3 yr, serum testosterone levels had been greater than 490 ng/dl. The ovaries were found to be normal by laparoscopy. Abdominal exploration revealed a 1-cm adenoma in the right adrenal. A part of the adenoma excised from our patient was homogenized and incubated with 5 microCi [14C]androstenedione. Five percent of the 14C was converted by the tumor homogenate to a metabolite with the same mobility as testosterone on LH-20 chromatography. After thin layer chromatography, the radiolabeled material together with 3H-labeled authentic testosterone were crystallized to a constant specific activity. The net rate of testosterone synthesis by the tumor was 26 pmol/mg wet tissue wt.h vs. 0.56 pmol/mg.h by a control adrenal homogenate. Thus, the tumor demonstrated a 50-fold increase in 17 beta-hydroxysteroid dehydrogenase activity compared to normal adrenal tissue. This is the first report to identify altered activity of a specific enzyme system in this syndrome of isolated adrenal testosterone overproduction.

17-Hydroxysteroid Dehydrogenases↗
PubMed1979

Early effects of thyrotropin on ribonucleic acid transcription in the thyroid.

Previous studies on the effects of TSH on the incorporation of labeled precursors into RNA have demonstrated an increase in the percentage of label in the phosphorylated nucleotide precursors of RNA. To avoid this nonspecific effect of TSH, we chose to measure RNA transcription in a system which uses exogenous phosphorylated precursors. Isolated nuclei were prepared from the thyroids of dogs which had been injected 90 min earlier with TSH. TSH caused a mean increase of 168% above control in total transcriptional activity, 193% in polymerase II-mediated (alpha-amanitin-sensitive) activity, and 155% in RNA polymerase I- and III-mediated (alpha-amanitin-resistant) activity. To determine whether part of this early effect of TSH was due to increased activity of RNA polymerase, incubations were also carried out in the presence of actinomycin D, which blocks transcription of endogenous template but does not inhibit transcription of added synthetic template poly deoxyadenylic-deoxythymidylic acid (dA.dT). Under these conditions, about half of the TSH-induced increase in the transcription of endogenous template could still be detected. Thus part of the early effects of TSH on RNA synthesis appears to be mediated through increased polymerase activity as well as enhanced template activity.

Amanitins↗
PubMed1979

Nitrogenous compounds reversibly inhibit the adenosine 3',5'-monophosphate response to thyrotropin: this effect is dissociated from altered guanine 3',5'-monophosphate levels.

Nitrogenous compounds were studied for their effect on cGMP levels in the thyroid. Several agents, including sodium nitrite and hydroxylamine, could generate a rise of over 100-fold in cGMP. At a concentration of 20 mM, HN2OH and NaNO2 significantly reduced cAMP levels previously generated by 0.5 mU/ml TSH. If the slices were rinsed and placed in new buffer without the latter nitrogenous compound, the cAMP response to TSH was restored even though intracellular cGMP levels remained elevated. Thus, the counterregulatory effect of these agents on cAMP levels is not correlated with the presence of high levels of cGMP per se. Both the rise in cGMP and the fall in cAMP could still be detected when Ca++ was deleted from the incubation medium, in contrast to other reported stimuli that elevate cGMP levels in the thyroid.

Animals↗
PubMed1978

Time course of thyrotropin-dependent protein phosphorylation in thyroid slices.

The time course of TSH-dependent protein phosphorylation was studied in calf thyroid slices labeled in vitro with 32Pi. Several of the proteins identified by two-dimensional electrophoresis displayed striking increases in 32P labeling in the presence of TSH. Phosphorylation of histones H3 and H1 (two subgroups) was enhanced about 3.7-and 10-fold, respectively, after incubation with TSH (15 mu/ml) for 70 min. Histone phosphorylation showed a lag after exposure to TSH; a major increase occurred only after 30-min incubation but then increased progressively up to 2 h. The lag in histone phosphorylation was also observed with slices prelabeled with 32P before the addition of TSH. In contrast, phosphorylation of a minor basic protein, A5 was also increased by 15 mU/ml TSH but displayed different kinetics, increasing substantially at 10 min. This time course correlates well with the rise in intracellular cAMP levels and protein kinase activity in thyroid slices after TSH.

Animals↗
PubMed1977

Effect of increased iodide intake on thyroid function in subjects on chronic lithium therapy.

Thyroid function tests were obtained in 10 patients on chronic lithium therapy before and after the administration of potassium iodide 250 mg q.i.d. Mean serum TSH rose by 8.9 muU/ml and mean serum T3 rose from 70 to 101 ng/dl. Two patients became hypothyroid; a third showed a rise in TSH without any change in T3 or T4. A fourth patient developed hyperthyroidism probably secondary to the Jod-Basedow phenomenon. Pharmacologic doses of iodine should be administered with caution to patients on chronic lithium therapy.

Adult↗
PubMed1976

Effect of caloric restriction and dietary composition of serum T3 and reverse T3 in man.

To evaluate the effect of caloric restriction and dietary composition on circulating T3 and rT3 obese subjects were studied after 7-18 days of total fasting and while on randomized hypocaloric diets (800 kcal) in which carbohydrate content was varied to provide from 0 to 100% calories. As anticipated, total fasting resulted in a 53% reduction in serum T3 in association with reciprocal 58% increase in rT3. Subjects receiving the no-carbohydrate hypocaloric diets for two weeks demonstrated a similar 47% decline in serum T3 but there was no significant change in rT3 with time. In contrast, the same subjects receiving isocaloric diets containing at least 50 g of carbohydrate showed no significant changes in either T3 or rT3 concentration. The decline in serum T3 during the no-carbohydrate diet correlated significantly with blood glucose and ketones but there was no correlation with insulin or glucagon. We conclude that dietary carbohydrate is an important regulatory factor in T3 production in man. In contrast, rT3 concentration is not significantly affected by changes in dietary carbohydrate. Our data suggest that the rise in serum rT3 during starvation may be related to more severe caloric restriction than that caused by the 800 kcal diet.

Adult↗
PubMed1976

The effect of aspirin and indomethacin on the TRH response in man.

A double-blind study of the effect of two inhibitors of prostaglandin synthesis on the TRH stimulation of serum TSH and prolactin was carried out in 35 normal males. The subjects were evaluated before and after the administration of indomethacin or aspirin for one week. Both indomethacin and aspirin lowered plasma prostaglandin E and F levels significantly. Indomethacin treatment had no effect on the serum TSH or prolactin response to 100 mug TRH or the serum T3 and T4 levels. In contrast, aspirin treatment significantly decreased the serum TSH response to TRH and significantly lowered mean total serum T3 (RIA) and T4 (D). There was no effect on the prolactin response to TRH. These findings suggest that aspirin blocks TRH responsiveness by a mechanism other than the inhibition of prostaglandin synthesis, probably by its previously demonstrated effect on increasing the fraction of unbound thyroid hormone.

Adolescent↗
PubMed1975

Effect of PGE1 and TSH on cAMP-dependent protein kinase activity in the thyroid.

PGE1, like TSH, can increase cAMP-dependent protein kinase activity in calf thyroid slices. The intracellular levels of cAMP produced by either of these agents alone appeared to correlate well with the degree of kinase activation. PG synthesis did not appear to be necessary for TSH action in this system, since indomethacin, and inhibitor of prostaglandin synthesis, did not alter either cAMP levels or kinase activity in slices incubated with TSH. Both the cAMP level and kinase activity rose when a submaximally effective dose of TSH was added to a maximal dose of PGE1. However, neither the cAMP levels nor the kinase activity produced by a maximal dose of TSH was affected by the addition of PGE1.

Animals↗
PubMed1975

Dopamine infusion acutely inhibits the TSH and prolactin response to TRH.

Ten normal males were given 100 mug TRH, and blood samples obtained for serum TSH and serum prolactin. After a period of at least one week, the TRH test was repeated while the patients were receiving a dopamine infusion. Both the TSH and prolactin response to TRH were inhibited by dopamine. Dopaminergic neurons may act through the pituitary-portal system to play a role in the regulation of TSH and prolactin secretion.

Adult↗
PubMed1975

Phosphoprotein phosphatase activity in the thyroid.

Phosphoprotein phosphatase activity in the calf thyroid was found in various subcellular fractions. The relative amount in each fraction varied according to the substrate used: The 500g fraction had the highest specific activity when protamine was used, while the 5000g fraction was highest when histone was used. Triton X-100 tended to increase activity in all the particulate fractions, the greatest change being found in the 105,000g pellet. DEAE chromatography of the 105,000 g supernatant resolved at least three peaks of phosphoprotein phosphatase activity.

Animals↗