Ornithine decarboxylase activity in rat pituitary glands.
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Biomedical subjects
Publications and source records attributed to G N Burrow.
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Thyrotropin (TSH) stimulation of ornithine decarboxylase (ODC) activity and polyamine levels was studied in vitro in rat thyroids. The elevation in ODC activity was related to the concentration of TSH in the incubation medium with peak activity at a concentration of 25mU/ml. ODC activity with 50 mU/ml of TSH was 3 to 5-fold higher than control activity at 5 h of incubation; this stimulation was enhanced by the addition of 0.5 mM 3-isobutyl-l-methyl xanthine (MIX), a phosphodiesterase inhibitor. Dibutyryl cyclic AMP (DbcAMP) also stimulated ODC activity with a dose response up to 2.0 mm. The increase in ODC activity with TSH and MIX was prevented by incubation with actinomycin D (10 microgram/ml) or puromycin (0.2 mM). Putrescine concentrations in rat thyroids rose to three times basal levels after 6 h of incubation with TSH and MIX; no significant elevation in spermidine or spermine was observed after up to 7 h incubation. The increase in tissue putrescine preceded a rise in [3H]uridine incorporation into acid-soluble material that occurred at 7 h. The results suggest that stimulation of thyroid ODC activity by TSH is mediated by a cyclic AMP; the data further are consistent with a role for polyamines in the control of RNA synthesis in the thyroid.
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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.
The relation of one school's admission decisions to performance in medical school was examined by comparing accepted applicants who chose to attend other institutions with rejected applicants who went to those same institutions. When differences among schools were controlled, no effect of admission decisions was observed.
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To study and predict a set of screening decisions in a medical school admission process, a stratified sample (n = 864) was drawn to represent the range of applicants to the Yale University School of Medicine during a single year. A smaller sample from the following year's applicants was drawn in a similar fashion for purposes of cross-validation. Prior to the prediction of screening decisions, a set of independent variables was selected by a factor analytic procedure from credentials in an applicant's admission folder. These folder variables ranged in nature from quantitative measures of academic performance to demographic information and types of extracurricular activity. Two multivariate statistical procedures, Sonquist's Automatic Interaction Detection (AID) and linear discriminant analysis (LDA), were used to predict screening decisions. Measures of academic performance and ability proved to be the most effective predictors of screening decision, as evidenced in the final AID tree and the discriminant function.
To assess the effect of TRH on the secretion of hCG, TRH in doses of 25 to 500 mug was administered to 10 pregnant women of 6 to 12 weeks or 16 to 20 weeks of gestation. There was no significant change in the serum hCG concentration during the ensuing 90 min. In women 6 to 12 weeks pregnant, doses of 25 mug, 100 mug, or 500 mug TRH elicted similar increments to serum TSH. Women 16 to 20 weeks pregnant had a slightly higher baseline TSH and a greater TSH response to TRH than the 6-12 week pregnant group. Although hCG may be an important thyroid stimulator in the first trimester of pregnancy, its secretion is not affected by TRH.
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.
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The thyroids of two brothers aged 13 and 15 with congenital goitre, butanolinsoluble iodine in blood and which had pronounced decrease of immunoreactive thyroglobulin content in the thyroid were studied. Two types of thyroglobulin were identified. The first amounted to only about 200-300 mug/g wet tissue and was fully immunoreactive with anti normal human thyroglobulin antiserum (iTG-G). It was purified by affinity chromatography. The other was mainly associated with intracytoplasmic membranes, amounted to about 8 mg/g wet tissue and was only partially immunoreactive (piTG-G). Both had abnormal amino acid compositions but only iTG-G showed a decreased carbohydrate content. Surprisingly, piTG-G showed a normal iodination level (0-5%) and a normal iodoamino acid composition. Immunochemical studies performed on slices or cell-free fractions incubated in the presence of labelled amino acids and/or monosaccharides showed that: (1) thyroglobulin peptide chains were being synthesized and almost normally discharged into the cisternae of the rough endoplasmic reticulum; (2) incorporation of sugars into iTG-G was decreased; (3) sialyl- and galactosyltransferase activities were normal and the enzymes normally located, and (4) albumin which is present in the thyroid as the iodinated protein was probably not synthesized by the goitrous tissues. Two major abnormalities were detected by light and electron microscopy: absence or pronounced scarcity of colloid in the follicular lumina and overdistended endoplasmic reticulum cisternae. These observations are compatible with a defect in TG transport from the cell into the lumen as the cause of the goitre. Whether defective thyroglobulin export is basically related to abnormality of the protein structure or to another cause is discussed.
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.
TSH (1.0 U im) caused a 22-fold increase in thyroidal ornithine decarboxylase activity (ODC) 6 hours after administration in intact rats. Hypophysectomized rats treated with 1 U TSH showed a 5-fold increase in thyroid ODC activity. This stimulation appeared to be specific for TSH since hormones known to induce ODC activity in other target tissues, such as ACTH or LH, showed no significant stimulation. DIBUTYRYL CYCLIC AMP and aminopylline caused a 12-fold increase in ODC activity 5 hours after administration. Prostaglandins have also been implicated in the TSH-induced stimulation of cyclic AMP. Indomethacin (1.0 mg/100 g body wt, ip), an inhibitor of prostaglandin synthesis, was administered 3 hours before TSH with a resulting 30% diminution (P less than .001) in ODC activity compared with the administration of TSH alone. To rule out the possibility that the increase in ODC activity with TSH might be due to increased thyroid hormone secretion, ODC activity was evaluated 6 hours after triiodothyronine administration (60 mug/100 g body wt), and no significant increase in thyroid ODC activity was found. Stimulation of ODC activity was 90% inhibited by the intraperitoneal administration of actinomycin D (80 mug/100 g body wt) or cycloheximide (400 mug/100 g body wt) given simultaneously with TSH. These results indicated that TSH specifically stimulated thyroid ODC activity, which may be important for the growth-promoting action of the hormone on the thyroid gland. This action may be mediated by cAMP and prostaglandins and may require new protein synthesis.
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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.
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.