[Comparative study of physico-chemical and biological properties of human somatotropin produced by genetic engineering and isolated from the pituitary gland]. / Sravnitel'noe issledovanie fiziko-khimicheskikh i biologicheskikh svoistv somatotropina cheloveka, poluchennogo gennoinzhenernym metodom i vydelennogo iz gipofizov.

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 lipotropic effect of STHbio in vivo was less prolonged as compared with that of STHhyp, while in vitro it was only slightly expressed in isolated rabbit fat tissue. The effect did not depend on the hormone dose, apparently due to either absence of the hormone modified forms in the STHbio preparation or other hypophyseal contaminating substances responsible for the lipotropic activity. STHbio, similarly to STHhyp, did not stimulate DNA synthesis in blood serum-free culture of human fibroblasts. Studies of STHbio biological properties suggest that multifunctionality of native STHhyp appear to depend on intrinsic specificity of its molecule.

[The alpha subunit of glycoprotein hormones as a biochemical marker of pituitary tumors]. / Al'fa-sub''edinitsa glikoproteinovykh gormonov kak biokhimicheskii marker opukholei gipofiza.

Specific radioimmunoassay was developed for detection free glycoprotein hormone alpha-subunit (AS), by using AS prepared from highly purified human thyroid-stimulating hormone (TSH). The assay showed that the basal content of free serum AS in the majority of 24 females with hormonally pituitary tumors secreting somatotropic hormone (STH, growth hormone), prolactin or either and in 24 females with unfunctioning pituitary tumors was significantly higher the mean one in 12 females matched for the same age who had no endocrine diseases (control). The cultured cells of STH- and P-secreting tumors released excessive quantities of free AS along with STH and P into the medium with low glycoprotein holo-hormone levels. The content of AS changed little in 12 patients with non-functioning pituitary tumors despite the greatly increased serum TSH levels in response to the hypothalamic stimulator thyroid-releasing hormone. The findings suggest that free AS secreted into blood in excess despite hypothalamic control may be regarded as a biochemical marker of pituitary tumors.

[Important role of C-terminal amino acid sequence of the luteinizing hormone alpha-subunit in its recombination with the beta-subunit]. / Vazhnaia rol' C-kontsevoi aminokislotnoi posledovatel'nosti alpha-sub'edinitsy liuteiniziruiushchego gormona pri ee rekombinatsii s beta-sub'edinitsei

Five amino acid residues, i. e. serine, lysine, histidine and two tyrosine residues, are split from the C-end of the alpha-subunit of bovine luteinizing hormone by carboxypeptidase A. Gel-filtration through Sephadex G-100 demonstrated that the carboxypeptidase-treated alpha-subunit is not recombined with the native beta-subunit and does not form complex molecules of the hormone.

[Suppression of lipotropic action of human somatotropin by protease inhibitors]. / Podavlenie lipotropnogo deistviia somatotropina cheloveka ingibitorami proteinaz.

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%. Contrary to these protease inhibitors, the aminopeptidase inhibitor bacitracin did not affect the growth hormone action. Trasylol and methylamine did not diminish either basal or epinephrine-stimulated lipolysis in rabbit fat tissue. In vivo Contrical at the total dose of 5000 E infused 30 min before and 30 min after the growth hormone injection completely abolished the increase of plasma-free fatty acid level induced by the hormone. These data suggest that: 1) the inhibitor suppression of growth hormone lipotrophic action is not due to the inhibitor influence on lipolysis or on hormone action at the cell membrane level but is the result of direct protease inhibiton; 2) the late lipotrophic action of the growth hormone may require preliminary cleavage of the hormone molecule in which serine proteases may be involved.

[Immunoanalysis of free alpha-subunits of glycoprotein hormones in human blood serum and its relationship with pituitary glycoprotein hormones]. / Immunoanaliz svobodnoi alpha-sub"edinitsy glikoproteinovykh gormonov v syvorotke krovi cheloveka i ee vzaimootnosheniia s glikoproteinovymi gormonami gipofiza.

A radioimmunoassay test system has been designed for measurements of free alpha-subunit (AS) of glycoprotein hormones in human blood serum with a sensitivity of 0.15 ng/ml. This test system revealed the absence of a direct correlation between the levels of free AS and levels of glycoprotein hormones in the blood sera of women with various endocrine profile, this being indicative of the specificity of this test system, on the one hand, and, on the other, confirming the possibility of independent secretion by the pituitary of free AS into the blood. Basal blood serum level of free AS in normal subjects is low: 0.9 ng/ml in women aged 17 to 30. The level of free AS secretion in the blood of many patients with nonfunctioning tumors of the pituitary was found increased, this demonstrating the diagnostic significance of measuring free AS as a marker of such tumors.