Antigenic and immunogenic properties of totally synthetic peptide-based anti-fertility vaccines.
(33/3269)
In this study we describe the results of experiments in which a variety of totally synthetic luteinizing hormone releasing hormone (LHRH) vaccines were assembled and examined for their abilities to elicit antibody responses and induce sterility in mice. It is shown that totally synthetic vaccines consisting of a 15 residue-defined T cell epitope and the 10 residue LHRH epitope not only induced high titers of antibody but also induced sterility. This effect did not appear to correlate with antibody titer, antibody isotype or comparative antibody affinity, but may be related to the length of time for which antibodies are present to exert their influence. (+info)
Mimicry in primary rat hepatocyte cultures of the in vivo perivenous induction by phenobarbital of cytochrome P-450 2B1 mRNA: role of epidermal growth factor and perivenous oxygen tension.
(34/3269)
Treatment of male rats with phenobarbital (PB) results in a perivenous and mid-zonal pattern of cytochrome P-450 (CYP)2B1 mRNA expression within the liver acinus. The mechanism of this zonated induction is still poorly understood. In this study sinusoidal gradients of oxygen and epidermal growth factor (EGF) besides those of the pituitary-dependent hormones growth hormone (GH), thyroxine (T4), and triiodothyronine (T3) were considered to be possible determinants for the zonated induction of the CYP2B1 gene in liver. Moreover, heme proteins seem to play a key role in oxygen sensing. Therefore, the influence of arterial (16% O2) and venous (8% O2) oxygen tension (pO2), and of the heme synthesis inhibitors CoCl2 and desferrioxamine (DSF) on PB-dependent CYP2B1 mRNA induction as well as the repression by EGF and, for comparison, by GH, T4, and T3, of the induction under arterial and venous pO2 were investigated in primary rat hepatocytes. Within 3 days, phenobarbital induced CYP2B1 mRNA to maximal levels under arterial pO2 and to about 40% of maximal levels under venous pO2. CoCl2 annihilated induction by PB under both oxygen tensions, whereas desferrioxamine and heme abolished the positive modulation by O2, suggesting that heme is a necessary component for O2 sensing. EGF suppressed CYP2B1 mRNA induction by PB only under arterial but not under venous pO2, whereas GH, T4, and T3 inhibited induction under both arterial and venous pO2. Thus, in hepatocyte cultures, an O2 gradient in conjunction with EGF mimicked the perivenous induction by PB of the CYP2B1 gene observed in the liver in vivo. (+info)
Microsomal long-chain acyl-CoA thioesterase (carboxylesterase ES-4) is regulated by thyroxine.
(35/3269)
Long chain acyl-CoA thioesterase activity is mainly located in microsomes after subcellular fractionation of liver from untreated rats. The physiological function and regulation of expression of this activity is not known. In the present study we have investigated the effect of thyroxine on expression of carboxylesterase ES-4, the major acyl-CoA thioesterase of liver microsomes. Thyroidectomy of rats decreased the palmitoyl-CoA thioesterase activity to about 25% of normal activity. This decrease was accompanied by similar decreases at the protein and mRNA levels (31% and 57%, respectively, of controls). Treatment with thyroxine completely reversed the effect of thyroidectomy and resulted in elevated levels in both thyroidectomized and control rats. For reasons of comparison we also studied the possibility that ES-10 and ES-2, two other members of the same gene family, are affected by thyroxine. ES-10 was not changed at the protein or mRNA level by any of the treatments, while ES-2 expression in liver was decreased by thyroxine treatment. The data shows that changes in activity and expression of ES-4 correlate to thyroxine status in the rat suggesting a physiological regulatory role by this hormone. Since thyroxine regulates the expression of lipogenic enzymes, these results are consistent with a function for this microsomal acyl-CoA thioesterase in fatty acid synthesis and/or secretion, rather than in oxidative degradation of fatty acids. (+info)
Sensitivity of thyroid gland growth to thyroid stimulating hormone (TSH) in rats treated with antithyroid drugs.
(36/3269)
Antithyroid drugs and phenobarbital (PB) have been shown to promote thyroid tumors in rats. It has been proposed that increased thyroid-stimulating hormone (TSH) mediates the thyroid tumor-promoting effect of antithyroid drugs and PB, and is increased because of decreased thyroxine (T4) concentration. However, PB is much less effective than antithyroid drugs at increasing TSH. It has been proposed that small increases in serum TSH produced by PB treatment is sufficient to promote thyroid tumors. However, the level to which TSH must be increased to stimulate the thyroid gland has not been reported. Therefore, we have examined the effect of increasing serum TSH concentration on thyroid growth by measuring thyroid gland weight and thyroid follicular cell proliferation. Serum TSH concentrations were increased by feeding rats various concentrations of propylthiouracil (PTU) or methimazole (MMI) for 21 days. Serum total T4, free T4, total T3 (triiodothyronine), free T3, and TSH concentrations were measured by radioimmunoassay. Thyroid follicular cell proliferation was measured by autoradiography and expressed as a labeling index (LI). PTU and MMI treatments reduced total and free T4 more than 95% by day 21, whereas total and free T3 were reduced 60%. TSH, thyroid follicular cell proliferation and thyroid weight were increased 560%, 1400%, and 200%, respectively, by day 21. TSH was significantly correlated with thyroid weight and LI. Moderate increases in serum TSH of between 10 and 20 ng/ml increased the number of proliferating thyroid follicular cells, but had no effect on thyroid weight. These results support that small increases in serum TSH can be sufficient to stimulate thyroid follicular cell proliferation. Furthermore, thyroid follicular cell proliferation may be more useful than thyroid weight alone for assessing alterations in thyroid growth in rats treated with chemicals that produce only small to moderate increases in serum TSH. (+info)
Treatment of thyrotropin-secreting pituitary adenomas with octreotide.
(37/3269)
Five hyperthyroid patients with TSH-secreting pituitary adenoma were treated with octreotide. Acute administration of octreotide decreased plasma TSH levels in all patients (mean decrease, 50.6 +/- 14%). Treatment with octreotide (25-300 microg/day) for 2-360 weeks resulted in reductions in plasma TSH and alpha-subunit levels in three patients, and serum free thyroxine levels were normalized with concomitant clinical improvements such as disappearance of excessive sweating, tachycardia and finger tremors. In two patients, plasma TSH and free thyroxine levels were initially decreased, but tachyphylaxis occurred 3 and 10 weeks after the initiation of therapy. Mild to marked shrinkage of the tumor was observed 2-50 weeks later in four patients. Shrinkage of the tumor seems to be reversible in one case. Frequent bowel movements and epigastric discomfort occurred in two patient. Somatostatin receptor subtype 2 (sst2) mRNAs were detected in two adenoma tissues studied by RT-PCR. Long-term treatment with octreotide is effective in controlling hyperthyroidism and tumor growth in patients with TSH-secreting pituitary adenoma. (+info)
Long-term treatment with bromocriptine of a plurihormonal pituitary adenoma secreting thyrotropin, growth hormone and prolactin.
(38/3269)
A 48-year-old female presented with acromegaly, amenorrhea and hyperthyroidism associated with high serum free T4 levels and measurable TSH concentrations. The administration of GHRH induced significant increases in GH, PRL and TSH. Conversely, intravenous infusion of dopamine or oral administration of bromocriptine effectively inhibited GH, PRL and TSH secretion. Serum alpha-subunit levels were neither affected by GHRH, dopamine nor bromocriptine. Transsphenoidal surgery was performed and immunostaining of the tissue showed that the adenoma cells were positive for GH, PRL or TSH. The patient was treated with bromocriptine at a daily oral dose of 10 mg after surgery. Serum TSH were initially suppressed but returned within reference intervals with persistent normalized free T4 levels. Serum PRL became undetectable and GH levels were stable around 6 ng/ml except the periods of poor drug compliance, when serum TSH, GH and PRL levels rose considerably. The patient was followed-up for 10 years without any change in the residual adenoma tissues as detected by magnetic resonance imaging. These findings suggest that long-term bromocriptine therapy is effective in treating the hypersecretory state of a plurihormonal adenoma secreting TSH, GH and PRL. (+info)
A case of Graves' disease associated with autoimmune hepatitis and mixed connective tissue disease.
(39/3269)
The patient was a woman of forty-eight. Liver dysfunction was pointed out at the age of forty-five. She was admitted to hospital because of her hyperthyroidism. Her palmar skin was wet and her fingers were swollen like sausages. She had a diffuse and elastic hard goiter with a rough surface. The serum levels of free T3 (9.6 pg/mL) and free T4 (3.76 ng/dL) were high and that of TSH (0.11 microU/mL) was low. The activity of TSH-binding inhibitory immunoglobulin (TBII) was 89%. The uptake rate of 123I to the thyroid was 55.1% and the uptake pattern was nearly diffuse. The goiter was proved to contain several nodules by ultrasonography, but aspiration cytology showed no malignant cells. She was diagnosed to have Graves' disease with adenomatous goiter. She also had high ALT (34 IU/L) and gamma-globulin (1.97 g/dL). She had positive antinuclear antibody (speckled type), positive anti-ribosomal nuclear protein antibody, and positive LE cell phenomenon. The liver biopsy revealed mononuclear cell infiltration with fibrosis in the portal area. These data indicated that she also had autoimmune hepatitis (AIH) and mixed connective tissue disease (MCTD). The analysis of human leukocyte antigen (HLA) showed positive A11 which had been reported to relate to Graves' disease, and positive DR4 which had been reported to relate to AIH and MCTD. These results suggested that HLA would determine susceptibility to three distinct autoimmune diseases in this case. (+info)
A case of congenital hypopituitarism: difficulty in the diagnosis of ACTH deficiency due to high serum cortisol levels from a hypothyroid state.
(40/3269)
A three-month-old boy presented congenital hypopituitarism in which the hypothyroid state masked ACTH deficiency. Multiple anterior pituitary hormone deficiencies, including ACTH, were finally confirmed. High basal serum cortisol levels (up to 45.1 microg/dl) were observed during a stressful episode before L-thyroxine replacement therapy was started. Decreased morning serum cortisol levels (5.0 microg/dl or below) were observed on the sixth day of L-thyroxine replacement therapy despite mild hypoglycemia (lowest serum glucose level of 50 mg/dl). ACTH deficiency was then confirmed by insulin-induced hypoglycemia test (peak serum cortisol level of 4.9 microg/dl). The present findings showed that serum cortisol levels can be high during a stressful episode in an infant with ACTH deficiency and a coexisting hypothyroid state. Thus, the diagnostic evaluation of adrenal function soon after L-thyroxine replacement therapy is important in order to verify a possible subclinical ACTH deficiency, even in the presence of high serum cortisol levels before L-thyroxine replacement therapy. (+info)