[Adenylate- and guanylate cyclase systems in pathology of the adrenal glands]. / Adenilat- i guanilattsiklaznye sistemy pri patologii nadpochechnikov.

The authors have summed up the results of a study of the activity of adenylate and guanylate cyclase system in the adrenals of patients with the Icenko-Cushing disease and syndrome and in the adrenals of experimental animals after unilateral adrenalectomy and in ACTH administration. It has been established that the biochemical mechanisms of compensatory hypertrophy of the adrenals in the normal and pathological tissue differ significantly. It has been shown for the first time that an increase in the basal activity of adenylate cyclase, resulting in the restoration of the initial hormonal level, is an obligatory condition for the compensation of organ function. Disorder in hormonal regulation of adenylate cyclase and diverse changes of the cyclase activity may indicate to the transition of tissue into a pathological state. Cyclic changes of the basal and stimulated activity of cyclases and protein kinases have been established for the first time in the adrenals of animals during administration of 2.5 units of ACTH for 5-40 days. The importance of detected changes in the mechanism of ACTH proliferative action is discussed.

[Biologically active fragments of protein hormones]. / Biologicheski aktivnye fragmenty belkovykh gormonov.

As shown in a number of experiments, corticotropin-like and opiate hormones are synthesized in a body as high molecular protein precursors, involving their biologically-active fragments. Pharmacological properties and perspectives for practical use of somatotropin fragments, synthetic opiate peptides as well as the peptides active in stimulation of pancreatic hormones secretion are considered in details.

[Adenylate and guanylate cylase system function in human hyperplastic adrenals in Itsenko-Cushing disease]. / Sostoianie adenilat- i guanilattsiklaznoi sistem v giperplazirovannykh nadpochechnikakh cheloveka pri bolezni Itsenko-Kushinga.

The content of cyclic nucleotides and the activity of adenylate and guanylate cyclases as well as of cAMP phosphodiesterase in the human hyperplastic adrenals were determined after one- and two-step bilateral adrenalectomy for Itsenko-Cushing's disease. A decrease in cGMP concentration and a corresponding increase in cAMP/cGMP correlation were seen in the 2nd hyperplastic adrenal comparatively to those in the 1st one. An enhanced basal activity of adenylate cyclase and its lowered sensitivity to ACTH were found in the 1st and the 2nd adrenals. These changes correlate with a rise in the blood ACTH concentration in patients after the ablation of one adrenal. It is suggested that the augmented adenylate cyclase activity leads to an increased activation of steroidogenesis enzymes in the rest adrenal, ensuring the elevated rate of corticosteroid secretion. The nature of changes in guanylate cyclase activity is contrary to that of adenylate cyclase; namely, guanylate cyclase basal activity of the 2nd hyperplastic adrenal was shown to be lower than that of the 1st one. The cAMP phosphodiesterase activity in the 1st and the 2nd adrenals remained unchanged.

[Changes in cyclic nucleotide metabolism in compensatory adrenal hypertrophy (following unilateral adrenalectomy)]. / Izmeneniia v metabolizme tsiklicheskikh nukleotidov pri kompensatornoi gipertrofii nadpochechnikov (posle odnostoronnei adrenaléktomii).

The cyclic nucleotide content, adrenocortical adenylatecyclase, guanylatecyclase, cAMP and cGMP phosphodiesterase activity, as well as the blood corticosteroid content of guinea pigs were determined at the different periods after bilateral adrenalectomy. The raised basal adenylatecyclase effect was also seen during compensatory hypertrophy of the sole adrenal. The response of adenylatecyclase to ACTH and Na is also enhanced at this moment. It is suggested that a physiological increase in the blood ACTH concentration, resultant of unilateral adrenalectomy, intensifies the adenylatecyclase catalytic activity and does not induce enzyme desensitization. The guanylatecyclase activity grows. It was established that changes in both cyclase activities are dependent on the postoperative time and are equal by character. The alteration of adenylatecyclase state always leads to the rise of guanylatecyclase activity. Changes in the cAMP and cGMP phosphodiesterase activity were not observed.

[Amino acid sequence of seiwhale somatotropin]. / Aminokislotnaia posledovatel'nost' somatotropina seivala.

Thirteen homogenous peptides were isolated from the chymotryptic hydrolysate of seiwhale somatotropin. The amino acid composition and sequence of the chymotryptic peptides were determined. Two large peptides were isolated from the tryptic hydrolysate of the performic acid-oxidized somatotropin. One of them had 20 amino acid residues and contained cysteic acid; the other one consisted of 31 residues and contained tryptophane and numerous leucine residues. The amino acid sequence of tryptic peptides was established after their hydrolysis with chymotrypsin. Based on these and earlier published data a complete amino acid sequence of seiwhale somatotropin comprising 190 amino acid residues was proposed. O comparison of primary structure of somatotropins from 6 different sources revealed the most conservative and variable regions of the hormone polypeptide chain.

[Adenylate cyclase activity and cyclic nucleotide content in human adrenal tumors under Icenko-Cushing syndrome]. / Aktivnost' adenilattsiklazy i soderzhanie tsiklicheskikh nukleotidov v opukholiakh nadpochechnikov cheloveka pri sindrome Itsenko--Kushinga.

The adenylate cyclase activity and cyclic nucleotide content in excised human adrenal tumours (Icenko-Cushing syndrome) were determined. The experimental data were compared to those obtained for hyperplastic adrenals. All adrenal tumours under study revealed a decreased cAMP level, an increased cGMP level and a resulting decrease of the cAMP/cGMP ratio. In malignant adrenal tumours the adenylate cyclase activity was sharply increased in comparison with that in hyperplastic adrenals. In the majority of malignant tumours the adenylate cyclase response to ACTH was either altogether absent or sharply decreased. In benign adrenal tumours the basal activity of the enzyme was unchanged and the enzyme response to ACTH was essentially normal. The decrease of adenylate cyclase response to ACTH in malignant tumours is apparently not due to the impaired catalytic activity of the enzyme, since its response to stimulation by sodium fluoride remains unaffected. In some tumours (one malignant and two benign ones) a non-specific stimulation of adenylate cyclase by hormones, which are not natural activators of the enzyme was observed. It was assumed that these changes are due to the damage of hormonal receptors in adrenal tumours.

[Hormonal regulation of estrogen and progesterone receptor biosynthesis in human endometrial tissue culture]. / Gormonal'naia reguliatsiia biosinteza retseptorov éstrogenov i progesterona v kul'ture tkani éndometriia cheloveka.

Estradiol and progesterone effects on the biosynthesis of estrogen and progesterone cytoplasmic receptors have been studied in the endometrium culture tissue of pregnant women. It was established that in a 48-hour culture estradiol stimulated the biosynthesis of its own and progesterone receptors. Under the same conditions progesterone stimulated the biosynthesis of estrogen receptors but did not affect the biosynthesis of its own receptors.

[Effect of ACTH in the biosynthesis of prostaglandins, adenosine cyclic monophosphate and steroids in the adrenal cortex of rabbits in vivo]. / Vliianie AKTG na obrazovanie prostaglandinov, tsiklicheskogo 3', 5'-adenozinmonofosfata i steroidov v kore nadpochechnikov krolikov v usloviiakh in vivo.

The effect produced by intravenous injection of ACTH to rabbits on the content of prostaglandins E and F (PGE and PGF) in the adrenal glands was studied. At the same time a determination was made of the cAMP content in the adrenal glands and of the peripheral blood corticosterone concentration. PGE and PGF were revealed in the adrenal cortex in concentrations of 199--550 and 271--335 pg/g respectively. After a dose of 50 Units there was a 2--3-fold rise of PGE, and a 1 1/2-fold rise of the PGF content. PG synthesis was elevated maximally in the adrenal glands 15 minutes after the ACTH injection, remaining at this level for 60 minutes; similar dynamics was revealed for the cAMP and corticoterone formation. The results obtained indicated that, along with intensification of the steroids and cAMP formation, ACTH stimulated PG synthesis in the adrenal glands. These data permit a suggestion to be made that PG participated in the ACTH action on the adrenal glands.

[Prostaglandin regulation of the sex hormone receptor content in human decidual tissue]. / Regulirovanie prostaglandinami soderzhaniia retseptorov polovykh gormonov v detsidual'noi tkani cheloveka.

Prostaglandin F2 alpha (PGF2 alpha) and its synthetic analog, 15-methyl-PGF2 alpha effects on the receptor content of estrogens and progesterone in the human decidual tissue were studied in vitro and in vivo experiments. The receptor content in vivo experiments was determined by Sketchard's technique and in vitro by the saturation method. Three hours after intravaginal administration of 15-methyl-PGF2 alpha suppositories to pregnant women the level of estrogen and progesterone receptors in decidual tissue cytosol significantly increased. Affinity of receptors with hormones remained unchanged. 10, 20, 50 and 100 mcg/ml concentrations of PGF2 alpha produced a significant and dose-dependent increase in the receptor content of estrogens following 15, 30, 60 and 180 minutes incubation of decidual tissue sections. The receptor level of progesterone remained unchanged. In experiments with inhibitors of protein and RNA biosynthesis, it was shown that an augmentation of the estrogen receptor content under PGF2 alpha action is not associated with biosynthesis of receptors de novo.

[Effect of various 1,3,5(10)-estratrien derivatives on the estrogen receptor transport into the nucleus in the guinea pig uterus]. / Vliianie razlichnykh proizvodnykh 1,3,5(10)-éstratriena na transport retseptora éstrogenov v iadro v matke morskoi svinki.

The capacity of five derivates of 1, 3, 5 (10)-estratrien to be transported together with estradiol receptor from the cytoplasm into the nucleus in the uterus of sexually immature guinea pig was investigated. The extent of this transport was assessed by the amount of estrogen receptor in the nucleus following incubation of the uterine slices in the presence of the compound tested (2.5.10(-7) M). The content of estrogen receptor in the nucleus of the intact guinea pig uterus served as control. Incubation of the uterine slices with compounds containing 17 beta-hydroxyl group (2-brom-1, 3, 5 (10)-estratriendiol-3, 17 beta, 4-brom-1,3,5 (10)-estratriendiol, 3, 17 beta, 1, 3, 5 (10)-estratrienol-17 beta), led to a 1.9--4.2-fold increase in the content of nuclear estrogen receptor, this pointing to the transport of the estrogen receptor complex with these compounds into the nucleus. Two compounds (1, 3, 5 (10) estratrienol-3 beta and 3-methoxy-1, 3, 5 (10)-estratrien) contained no 17 beta-hydroxyl group and failed to increase the contents of the estrogen receptor in the nucleus in comparison with control. 17 beta-hydroxyl group is apparently necessary for the formation of conformative changes in the receptor molecule transforming the steroid-receptor complex into the active one, capable of transporting into the nucleus.

[Lipolytic effects of a synthetic tetradecapeptide, corresponding to 31-44 amino acid sequence of human somatotropin]. / Kharakteristika zhiromobilizuiushchego deistviia sinteticheskogo tetradekapeptida, sootvetstvuiushchego aminokislotnoi posledovatel'nosti 31-44 somatotropina cheloveka.

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. Both in rats and rabbits the in vivo lipolytic effect of native somatotropin was pronounced only after a 2-hr latency. Actinomycin D and cycloheximide did not prevent the lipolytic effect of the tetradecapeptide in isolated adipose tissue; however, this effect was not exerted in the absence of Ca2+. The hexapeptide fragment of tetradecapeptide was inactive in rats in vivo, but had a slight effect an isolated rat adipose tissue when taken at high doses. Thus, the lipolytic effect of the tetradecapeptide requires Ca2+ and is more pronounced in rabbits than in rats. Contrary to somatotropin, the effect of tetradecapeptide is fast and independent of RNA and protein synthesis. These data and previously shown tetradecapeptide lipolytic effect on isolated human adipose tissue suggest that the tetradecapeptide possesses structural features required for the lipolytic effect of the whole hormone.

[Study of the possibility of using the "artificial pancreas" in the treatment of diabetes mellitus]. / Izuchenie vozmozhnosti primeneniia apparata "iskusstvennaia podzheludochnaia zheleza" v lechenii bol'nykh sakharnym diabetom.

A short survey of the literature data on the use of an artificial pancreas in the treatment of patients suffering from diabetes mellitus is presented. These data point to the high efficacy of the artificial pancreas in diabetic patients, this confirming the author's personal observations.

[Sex hormone regulation of progesterone and estradiol receptors in the cytosol of human endometrium in normal and pathologic pregnancy]. / Regulirovanie polovymi gormonami soderzhaniia retseptorov progesterona i estradiola v tsitozole endometriia cheloveka pri normal'noi i patologicheskoi beremennosti.

Hormonal control of progesterone and estradiol receptors was studied in the cytozol of short-lived culture of human endometrium in normal and undeveloping pregnancy. Endometrium was cultivated in the presence of estradiol or progesterone for 16 hours. In cultivation of normal endometrium with estradiol the content of estradiol receptors increased 4-fold in comparison with unstimulated tissue, and of progesteron receptors--3-fold. In cultivation of normal endometrium with progesterone the content of estradiol receptors rose 4--5-fold, and of progesterone receptors--3-fold. In cultivation of pathological endometrium with estradiol or progesterone the number of estradiol receptors was only doubled, and of progesterone receptors--increased only 1 1/2 times, this pointing to a diminished sensitivity of pathological endometrium to the regulating action of sex hormones.

PIP: Hormonal control of progesterone and estradiol receptors was studied in the cytozol of a short-lived culture of human endometrium in both normal and undeveloping pregnancy. Endometrium was cultivated in the presence of estradiol or progesterone for 16 hours. In the cultivation of the normal endometrium with estradiol, the content of estradiol receptors increased 4-fold in comparison with the normal tissue, and the progesterone receptors increased 3-fold. In the culturation of the normal endometrium with progesterone, the content of the estradiol receptors rose 4-5-fold while the progesterone receptors increased 3-fold. In the cultivation of the pathological endometrium with either estradiol or progesterone, the number of estradiol receptors only doubled and the progesterone receptors increased only 1-1/2 times. This points to a diminished sensitivity of a pathological endometrium to the regulating action of sex hormones. (Authors' modified)