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Biomedical subjects

R Johansson

Publications and source records attributed to R Johansson.

At least 163 records · Page 9Linked to original sources

Human adipose tissue in culture V. Studies on the metabolic effects of insulin.

Specimens of human adipose tissue were cultured for one week with or without the addition of insulin. The basal as well as the noradenaline-stimulated lipolysis were enhanced in the explants cultured with insulin, showing that the long-term effect of the hormone is lipolytic. However, an acute antilipolytic effect of insulin could be demonstrated in these explants in the subsequent short-term incubations. The basal rate of glucose incorporation into the lipids was enhanced in the explants cultured with insulin. When insulin was added in the short-term incubations these explants did not further respond to the hormone while this was the case with the explants cultured without insulin. Thus, it seems that prolonged exposure to insulin leads to a diminished acute effect of the hormone on glucose metabolism. However, the same explants responded to the antilipolytic effect showing that insulin was able to bind itself to the membrane. The activities of hexokinase (HK), glucose-6-phosphage dehydrogenase (G6PDH), pyruvate kinase (PK) and lactate dehydrogenase (LDH) were increased in large fat cells both in freshly excised tissue and in cultured explants. However, the activity of phosphofructokinase (PFK) did not correlate with the cell size. The presence of insulin during the culture period enhanced the activities of G7PDH, PK, and LDH, while this was not found for HK or PFK. The data thus suggest that the metabolic capacity of human fat cells is enhanced by long-term exposure to insulin. Although enzyme induction could be shown for G6PDH, PK and LDH it seems unlikely that this is of importance for the increased rates of glucose metabolism in these explants since the rate-limiting enzymes, HK and PGK, were not increased. Most probably, then, this stimulating effect of insulin is exerted on the membrane and the rate of glucose transport.

Adipose Tissue↗

Effect of some synandrogens and antiandrogens on the conversion of testosterone to dihydrotestosterone in the cultured rat ventral prostate.

The actions of prolactin, insulin and cortisol on the conversion of testosterone to dihydrotestosterone in the cultured rat ventral prostate were examined in conditions in thich they have been demonstrated to act synergistically with testosterone on the macromolecule synthesis of the prostate. On the other hand oestradiol, progesterone and cyproterone were tested similarly in conditions where they have been shown to be effective antiandrogens. The metabolism of testosterone to dihydrotestosterone was found to be extremely rapid and approximately 70% of the radioactive steroids in the tissue was dihydrotestosterone from 5 min onwards, but only insignificant amounts of dihydrotestosterone were found in the culture medium during the first hour. Physiological concentrations of the synandrogens did not alter the metabolism of testosterone or the accumulation of the steroids into the tissue. Oestradiol, progesterone and unlabelled testosterone in a 500-fold concentration markedly reduced th e conversion of tritiated testosterone to dihydrotestosterone while cyproterone and dihydrotestosterone had no effect. The possible role of other hormones in the alteration of testosterone metabolism in the target organs as the mechanism of synandrogenic or antiandrogenic action is discussed.

Animals↗

Effect of prolactin, growth hormone and insulin on the uptake and binding of dihydrotestosterone to the cultured rat ventral prostate.

The effects of prolactin, growth hormone and insulin on the total uptake and specific binding of tritiated dihydrotestosterone in the cultured rat ventral prostate were examined. In similiar conditions prolactin and insulin act synergistically with testosterone on the macromolecule synthesis of the prostate, but have no effect on the conversion of testosterone to dihydrotestosterone. The total uptake of tritiated dihydrotestosterone to the tissues was slightly, but not statistically significantly, increased by prolactin, insulin and growth hormone. The majority of the radioactive dihydrotestosterone in the tissue was in free form or very loosely bound. None of these three hormones altered the binding of tritiated dihydrostestosterone to the cytoplasmic receptors. Non-radioactive dihydrotestosterone, cyproterone and cyproterone acetate in 1000 fold excess strongly decreased the binding of tritiated dihydrotestosterone to the cytoplasmic reseptors and to the nuclei. That part of the binding, which was inhibited by the hormones was considered to represent the specific binding to the receptors. Insulin stimulated both the specific and the unspecific uptake of dihydrostestosterone to the nuclei. Prolactin only stimulated the specific uptake to the nuclei while growth hormone had no effect. Autoradiography of the nuclear fraction indicated a firm binding of tritiated dihydrotestosterone to the nuclei. The radioactivity of the other contaminating cell components in this fraction appeared to be negligible.

Animals↗

Plasma levels of imipramine and desipramine in man after different routes of administration.

With the object of studying the kinetics of imipramine and desipramine five healthy volunteers received single intramuscular, oral and intravenous doses and multiple oral doses of imipramine hydrochloride on different occasions. Two of the volunteers also received single intramuscular and oral doses of desipramine hydrochloride. Great interindividual differences were noted in the plasma concentrations of imipramine and the formed desipramine after single doses of imipramine hydrochloride. In all subjects more desipramine was formed after oral than after parenteral adminstration of imipramine. The bioavailability of an orally administered dose of imipramine ranged between 29.5 and 54.7%. The concentration of imipramine was generally lower in the blood cells than in the plasma, unlike the concentration of desipramine which was considerably higher in the blood cells. The half-lives of imipramine ranged from 4.0-17.6 hrs (M = 7.6 +/- 2.5) after single oral doses and between 9.2 and 20.2 hrs (M = 14.0 +/- 1.9) after multiple oral doses. The half-lives of the formed desipramine ranged between 13.5 and 61.5 hrs (M = 29.9 +/- 8.7) after multiple oral doses of imipramine hydrochloride. The observed mean steady-state plasma concentration after multiple oral doses of imipramine hydrochloride, 50 mg t.i.d. varied from 21.4-69.0 mug/1 (M = 38.2 +/- 8.7) for imipramine and from 33.7-136.0 mug/1 (M 72.3 +/- 19.5) for desipramine. The great difference in the ability to form desipramine after oral and parenteral administration of imipramine hydrochloride may have therapeutic consequences as imipramine and desipramine have differing pharmacological properties.

Administration, Oral↗

DNA and protein synthesis of prostatic cultures in relation to histological response under the influence of testosterone and its metabolites.

Testosterone as well as dihydrotestosterone and 5alpha-androstane-3beta, 17beta-diol were capable of maintaining, in rather low concentrations (0.02, 0.02 and 1.0 mug/ml, respectively), the histological structure of the rat ventral prostate in organotypic tissue culture. By means of histometrical analysis testosterone and dihydrotestosterone were found to be active in lower concentration (0.05 mug/ml) than adrostanediol. In addition to the visual evaluation of the structure of the explants their total DNA and protein content was measured as well as their rate of incorporation of tritiated thymidine and leucine. In a concentration of 1 mug/ml the response of the ventral prostate culture was almost equal to all the steroids. Androstanediol, however, caused no stimulation in lowest concentrations (0.02-0.1 mug/ml) and was not toxic in the highest concentrations (100 mug/ml) at which testosterone and dihydrotestosterone were definately cytolytic. When the serum from the culture medium was omitted even hormone concentrations close to the physiological level (0.003 mug/ml) could stimulate thymidine and leucine incorporation into the cultured ventral prostate.

Androstanes↗

RNA, protein and DNA synthesis stimulated by testosterone, insulin and prolactin in the rat ventral prostate cultured in chemically defined medium.

In an organ type tissue culture of the rat ventral prostate in a chemically defined medium insulin (0.08 IU/ml) stimulated the synthesis of RNA within 6-12 h, the synthesis of protein within 6-12 h and the synthesis of DNA within 2-4 days. Testosterone (10(-8)m) stimulated these synthetic processes somewhat more slowly: the synthesis of RNA within 12-24 h, protein within 12-24 h and DNA at 4 days. Rather high concentrations of insulin were needed while testosterone was effective at a physiological concentration. Prolactin (1000 ng/ml) stimulated the synthesis of RNA and protein, but not DNA, when added together with either testosterone or insulin, but was completely ineffective when added alone. The response times resembled those of insulin. The lower concentrations of prolactin were ineffective. Growth hormone, luteinizing hormone and follicle stimulating hormone did not stimulate the synthesis of RNA, protein or DNA even when added with testosterone. The results confirm the findings of the numerous in vivo experiments that the hypophyseal hormone prolactin has a direct effect on the ventral prostate.

Animals↗