[The hypothalamo-hypophyseal system in patients with multinodular colloid euthyroid goiter].

Eighty patients with multinodular colloidal euthyroid goiter were examined. Thyrotropin-releasing hormone (TRH) test was carried out in 22 patients and 7 healthy women. The results of the test indicate a clear-cut tendency to reduction of hypophyseal TTH reserve in patients with multinodular euthyroid goiter with enlarged thyroid.

[Humoral autoimmunity markers in autoimmune endocrine diseases].

To clarify the value of autoantibodies as risk factors of complications in various endocrine abnormalities, the incidence of autoantibodies to thyroid microsomal antigen (ATMA), thyroglobulin, and the surface antigens of the rat islet, adrenal cortex, adenohypophyseal cells and human skin fibroblasts was studied in patients with insulin-dependent mellitus (IDDM), at the onset of the disease and during one-year insulin therapy, non-insulin-dependent diabetes mellitus (NIDDM), Hashimoto thyroiditis, Graves' disease, diabetes associated with thyroidal dysfunction, euthyroid polynodular goiter, Schmidt and polyglandular syndromes and in the population. The antibodies were determined by ELISA. Polyclonal activation of the immune system was found in all abnormalities, except in polyglandular in children.

[Determination of autoantibodies to pancreatic beta-cells, non-islet endocrine cells and fibroblasts in patients with newly detected diabetes mellitus].

The clinical onset of insulin-dependent diabetes (IDD) is characterized by the onset of circulation of autoantibodies to beta-cells. Thirty-three newly detected IDD patients and 14 newly detected patients with noninsulin-dependent diabetes mellitus were examined for autoantibodies to antigen P 64-69, to surface antigen of islet cells, to thyrocyte microsomal fraction, thyroglobulin, hypophysis, fibroblasts; the levels of circulating immune complexes were measured as well. IDD debut was found associated with the appearance of antibodies to pancreatic islet cells, thyroid, thyroglobulin, hypophysis, fibroblasts, this indicating a polyclonal activation of the immunity system.

[An immunoenzyme method for determining autoantibodies to the microsomal antigens of human thyrocytes].

In order to investigate the role of autoantibodies in the pathogenesis of autoimmune thyroid diseases and for clinicoimmunological control of treatment, an enzyme-linked immunosorbent assay (ELISA) for the determination of autoantibodies against human thyroid microsomal antigens (TMA) was developed. ELISA was evaluated using sera from 156 patients with different thyroid pathology and diabetes mellitus and from 54 healthy donors. In parallel experiments the same sera were analyzed by an indirect immunofluorescence method for the presence of autoantibodies against TMA.

[Hypoinsulinemia, hyperglycemia and circulating antibodies to the islet cells during the development of streptozotocin diabetes in rats].

The time course of metabolic parameters and islet cell surface antibodies (ICSA) in low-dose streptozotocin (STZ)-induced diabetes in rats was studied, a total STZ dose being 160 mg/kg body weight. Two-phase diabetes development was observed. Initial mild hypoinsulinemia and hyperglycemia turned to more severe diabetes after day 24 which was preceded by the first ICSA peak at day 13.

[The morphology of diabetic nephropathy in experimental diabetes induced by low doses of streptozotocin].

Kidneys of 16 Wistar rats were examined by light and electron microscopy, immunofluorescence and biochemically for the transamidinase activity at various periods of experimental diabetes induced by the fractionated intraperitoneal administration of low (40 mg/kg) doses of streptozotocin. 18 rats of the same age and sex served as control. This model of diabetes is characterized by a gradual decrease of the serum immunoreactive insulin, increase of hyperglycemia, the presence of "insulitis" 19 days after the beginning of the experiment and the development of nephropathy in the genesis of which immune mechanisms might participate.

[Molecular biological aspects of the pathogenesis of diabetes mellitus].

The discovery of the key role played by the immune system in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) opens up new possibilities for its early diagnosis, at the stages preceding its clinical manifestation. Analysed are the markers of genetic susceptibility to IDDM associated with some major histocompatibility complex antigens (specifically with HLA-DR 3, HLA-DR4, and HLA-DQ), of the cellular and humoral anti-islet autoimmunity, as well as the origin of the islet-cell autoantigens. The markers' significance for the diagnosis and prognosis is discussed.

[Comparative study of physico-chemical and biological properties of human somatotropin produced by genetic engineering and isolated from the pituitary gland].

Human somatotropin hormono (STH), produced by means of gene engineering in the complex program "Human growth hormone", managed by the Academy of Sciences of the USSR, Ministry of Medical and Biological Industry of the USSR and Ministry of Public Health of the USSR, was shown to be similar in its physico-chemical properties to the main isoform of highly purified STH, isolated from human hypophysis. As distinct from the hypophyseal STH (STHhyp) containing minor isoforms of the hormone, the preparation of biosynthetic STH (des-Phe1-STH; STHbio) proved to be homogeneous. Studies of biological properties showed that STHbio exhibited high, similar to STHhyp, immunological, growth-stimulating and insulin-like activities as well as it possessed the lipotropic effect in vivo.

[The role of proteolytic processes in the stimulation of lipolysis in the adipose tissue by somatotropin, adrenocorticotropin and beta-lipotropin].

The influence of proteinase inhibitors on the lipotropic effect of somatotropic (STH), adrenocorticotropic (ACTH) and beta-lipotropic (LPH) hormones in adipose tissue was studied in vitro. The effect of STH was found to be completely dependent on the activity of tissue serine proteinases of trypsin and chymotrypsin types. The effect of LPH partly depended on serine proteinases of chymotrypsin type, whereas that of ACTH--on chymotrypsin and carboxylic proteinases.

[Effect of the synthetic tetradecapeptide corresponding to the amino acid sequence of human somatotropin 31-44 on rat blood and liver lipids].

Although synthetic tetradecapeptide, involving the 31-44 amino acid sequence of human growth hormone, exhibited a distinct lipolytic effect, content of triglycerides was not increased in rat blood and liver tissue during chronic experiments. At the same time, the level of atherogenic lipoproteins as well as activities of postheparin lipase and liver triglyceride lipase were also unaltered. The data obtained suggest that the tetradecapeptide studied stimulated simultaneously both lipolysis and oxidation of free fatty acids.

[Suppression of lipotropic action of human somatotropin by protease inhibitors].

The effect of protease inhibitors on the lipotrophic action of the human growth hormone was studied in rabbits in vivo and in vitro. The human growth hormone at a concentration of 25-100 micrograms/ml stimulated lipolysis in isolated rabbit perirenal fat tissue 3-5 fold. An addition of 250 or 500 E Trasylol or 5 mM methylamine to the incubation mixture inhibited the growth hormone lipotrophic effect by 50%.

[Chronic action of the fat-mobilizing fragment of human somatotropin on the fat content of fat depots and the plasma glucose level in rabbits].

The effect was studied of synthetic tetradecapeptide-the fat-mobilizing human somatotropin fragment 31-34--on the fat content in fat depot and glucode concentration in the rabbit blood plasma and urine. A marked decrease in subcutaneous (the nape region), perirenal, mesenteric and epididimal fat content, accompanied by partial replacement of the fatty tissue by the connective one, was seen 3 to 4 weeks after tetradecapeptide injection to rabbits. Peptide effect manifested itself only under condition of the inadequate diet and was especially pronounced in young animals.

[Lipolytic effects of a synthetic tetradecapeptide, corresponding to 31-44 amino acid sequence of human somatotropin].

A synthetic tetradecapeptide 31--44 developed a fast lipolytic effect in rats and rabbits in vivo and in vitro. The concentration of plasma fatty acid was maximal after 30 min following the injection and came down to the initial level after 60--120 min. The effect was prolonged when the tetradecapeptide was injected in the form of Zn-suspension.

[Primary structure of cyanogen bromide fragments of sei whale (Balaenoptera borealis) pituitary somatotropin].

5 fragments are isolated after the degradation of somatotropin from sei whale pituitary glands with cyanogen bromide: N-terminal 4-segmented; C-terminal 12-segmented with the internal disulfide bond; middle 25- and 30-segmented and a high molecular weight fragment following N-terminal tetrapeptide and bound with disulfide bond to 30-segmented fragment. Complete amino acid sequence of three shortest cyanogen bromide fragments is deciphered and N- and C-terminal sequence is investigated in two large fragments after their uncoupling under performic acid oxidation. Amino acid sequence is deciphered of a peptide obtained after trypsine hydrolysis of 30-segmented cyanogen bromide fragment.

[Effect of synthetic tetradecapeptide corresponding to 31-44 amino acid sequence of growth hormone on lipolysis in human adipose tissue].

Fat mobilyzing activity of synthetic tetradecapeptide, which corresponds in 31--44 amino acid sequence of human growth hormone, is studied in vitro in human fat tissue. The peptide at concentrations of 3--33 microng/ml considerably stimulated lipolysis in subdermal fat tissue, omentum and shoulder ateroma. Minimal efficient peptide concentration was 3 microng/ml in most experiments, sometimes it was 0.

[Lipid-mobilizing activity of a synthetic peptide identical to 33-44 fragment of human growth hormone].

The lipid-mobilizing activity of a synthetic peptide, NH2-Phe-Glu-Glu-Ala-Tyr-Ile-Pro-Lys-Glu-Gln-Lys-Tyr-Ser-Phe-COOH, corresponding to the 31-44 amino-acid sequence of human growth hormone, was studied. The peptide stimulated lypolysis upon administration to fasted rats and during incubation with isolated epidiymal adiposed tissue of rat and perirenal adiposed tissue of rabbit. The lipid-mobilizing effect of the peptide,unlike the corresponding effect of the native growth hormone, developed fast and was markedly pronounced 15-30 min after the incubation was started.