A radioimmunoassay, using a rabbit antiserum directed against thymosin a,, was employed to detect the presence of crossreacting peptides in rat tissues. Highest concentrations were present in thymus, but thymosin al crossreacting material was also detected in brain, liver, kidney, lung, and spleen, in amounts ranging from 15% to 65% of the quantities found in thymus. In each case, the major immunoreactive peptide, after extraction and purification by a procedure that avoids proteolytic modification, was identified as prothymosin a, a peptide containing %112 amino acid residues. Prothymosin a is believed to be the endogenous peptide from which thymosin a, and other fragments are formed by proteolytic modification during the preparation of thymosin fraction 5. No peptides corresponding in size and chromatographic behavior to thymosin a, were detected with the extraction procedure employed.

Objective: Variations in thyroid function are known to be associated with changes in adrenocortical activity. Previous studies in animals have suggested that long-standing hyperthyroidism may be associated with diminished adrenal functional reserve despite a continuing hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. In humans, there has been no direct assessment of adrenal secretory reserve in clinical thyrotoxicosis. This study aimed to assess adrenocortical reserve in response to low-dose ACTH, following dexamethasone suppression, in patients with severe thyrotoxicosis. Design and methods: Ten patients (four men and six women, 30-45 years) with severe long-standing thyrotoxicosis due to Graves' disease (n = 6) or toxic nodular goitre (n = 4) were studied at diagnosis and again when in a stable euthyroid state following drug therapy for 8-12 months. All patients underwent ACTH stimulation tests at 0800 h with ACTH 1-24 (Cortrosyn; 0.1 mg/kg body weight, i.v.) following overnight suppression of the HPA axis with dexamethasone (1 mg per os at 2300 h). Serum cortisol was assayed at ¹15, 0, 15, 30, 60 and 90 min after the administration of ACTH. Results: The mean (Ϯ S.D.) peak and delta cortisol responses to ACTH (634.5 Ϯ 164 nmol/l and 618 Ϯ 196 nmol/l respectively), as well as the net area under the response curve (36 769 Ϯ 12 188 nmol/l × min) in the hyperthyroid patients were significantly lower compared with the values when the same patients were euthyroid (911 Ϯ 157 nmol/l, 905 Ϯ 160 nmol/l and 57 652 Ϯ 10 128 nmol/l × min respectively; P < 0.005). Subnormal peak cortisol responses (<500 nmol/l) were observed in two severely toxic patients. The findings were independent of the cause of thyrotoxicosis. Conclusion: In patients with severe thyrotoxicosis, cortisol secretion in response to low-dose ACTH stimulation, following dexamethasone suppression, is lower in the hyperthyroid than in the euthyroid state. It appears that thyrotoxicosis is associated with subtle impairment of adrenocortical reserve.

Goat prothymosin alpha, a highly acidic polypeptide of pI3.5, 109 amino acid residues, has been isolated from lymphoid and non-lymphoid tissues of young female goats. Unlike rat, murine and porcine prothymosins alpha, goat prothymosin alpha appears at a higher concentration in the spleen compared with the thymus. The sequence of segments of the polypeptide involving known mutations has been determined, by automatic sequencing of its tryptic peptide fragments. The acidic amino acid-rich segment in the middle of the molecule, including residues 49-83, has not been sequenced. Goat prothymosin alpha closely resembles bovine prothymosin alpha, with only one substitution, proline for alanine at position 85. It also resembles human prothymosin alpha, with only three substitutions. It differs more significantly from rat and murine prothymosins alpha, by two deletions and three substitutions. The results show the highly conserved nature of the molecule, with substitutions at given positions only.

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