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Biomedical subjects

K Carlström

Publications and source records attributed to K Carlström.

At least 163 records · Page 9Linked to original sources

Serum levels of estrogens and of five 'steroid sensitive' proteins in early normal pregnancy.

Serum concentrations of sex hormone binding globulin (SHBG), pregnancy associated alpha 2-glycoprotein (alpha 2-PAG), caeruloplasmin (Cp), alpha 1-antitrypsin (alpha 1-At) and transferrin (Tf), unconjugated and total estrone, and unconjugated estradiol-17 beta were measured twice at a 4-5 week interval in 43 cases of early normal pregnancy (gestational weeks 6-19). Significant correlations between estrogen and protein levels in the total material were observed for all proteins except for Tf. However, within 2-week intervals of pregnancy, significant correlations were obtained only in certain intervals between estrogens on one hand and SHBG, Cp and alpha 1-At on the other. Significant correlations between rates of increase of estrogens and of proteins were obtained only at certain occasions for SHBG, Cp, Tf and alpha 1-At. The results indicate that, although estrogens may have a modulatory function in 'steroid-sensitive' protein synthesis, they are probably not the main physiological regulator.

Ceruloplasmin↗

Novel assay for pancreatic cellular damage: 1. Characterization of protein profiles in human pancreatic cytosol and purification and characterization of a pancreatic specific protein.

The protein patterns of cytosols from normal human pancreas and pancreatic carcinoma were studied by a two-dimensional separation technique using high-performance liquid chromatography followed by isoelectric focusing on polyacrylamide gels and visualization of the focused proteins by Coomassie Blue staining. Almost identical protein patterns were obtained for 20 different specimens from normal pancreas, whereas quite different protein patterns were found in 12 samples of pancreatic carcinoma. A major protein in normal pancreatic cytosol, not identical to any macromolecule previously tested as a marker for pancreatic function, was selected for further studies. The protein was not found in specimens of pancreatic carcinoma. It was purified by a single step chromatofocusing procedure, focused at pH 6.9, and moved as one single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 44,500 daltons. Total amino acid analysis revealed a high concentration of glutamic acid, leucine, and lysine. The purified protein had no amylase activity or lipase immunoactivity. It constituted approximately 2% of the total normal pancreatic cytosol protein. Later immunological studies have shown the protein to be highly specific for normal human pancreas, indicating a possible future use as a marker for pancreatic cell damage.

Adenocarcinoma↗

Dehydroepiandrosterone sulfate in saliva.

Concentrations of dehydroepiandrosterone sulfate (DHAS) in saliva and serum were determined in 11 healthy men aged 23-40 yrs, 55 healthy, non-medicated women aged 20-81 yrs and 13 healthy women aged 20-30 yrs, all taking combined oral contraceptives (OC). Serum DHAS was higher in men than in women of corresponding age and was negatively correlated to age in OC-free women. These sex- and age-related differences were not found for salivary DHAS. Salivary and serum DHAS values were poorly correlated and the ratios between salivary and serum DHAS were variable, with a tendency to higher values in older subjects. Low saliva/serum DHAS ratios were found in OC users. The lack of a uniform, unequivocal relation between DHAS concentrations in saliva and serum renders salivary DHAS assays unsuitable for clinical purposes.

Adult↗

Single drug polyestradiol phosphate therapy in prostatic cancer.

Serum concentrations of testosterone (T) and estradiol-17 beta (E2) were analyzed in prostatic cancer patients treated with 160, 240, or 320 mg polyestradiol phosphate (PEP) i.m. every fourth week as single drug therapy during a 6 month period. Estrogen effects on the liver were studied by analyzing serum levels of sex hormone binding globulin (SHBG) in the 320 mg group and compared with values obtained in patients treated with 80 mg PEP i.m. every fourth week + oral ethinylestradiol (EE2) 150 micrograms daily, or by orchidectomy. Orchidectomy levels of T were reached within 3 weeks in the 320 and 3 months in the 240 mg group. In the 160 mg group, mean T levels reached the upper limit of orchidectomy values after 6 months. Accumulation of E2 occurred to mean levels 1,300-2,500 pmol/L at 6 months. At 6 months, SHBG levels had increased to 617% of pretreatment values in the oral EE2 group, to 166% in the 320 mg group, and were unaffected by orchidectomy. No cardiovascular side effects occurred during single-drug PEP treatment.

Aged↗

Steroid-sensitive proteins, growth hormone and somatomedin C in prostatic cancer: effects of parenteral and oral estrogen therapy.

The effects of parenteral and parenteral plus oral estrogen therapy on the serum levels of sex hormone binding globulin (SHBG), pregnancy-associated alpha 2-macroglobulin (alpha 2-PAG), growth hormone (GH), and somatomedin C (SmC) were studied in 26 patients with prostatic cancer. Intramuscular polyestradiol phosphate treatment, yielding a mean serum level of estradiol-17 beta of 1,446 pM and a mean testosterone level of 4.5 nM, had no significant effects on alpha 2-PAG, GH, and SmC and increased SHBG levels only marginally. Combined treatment with intramuscular polyestradiol phosphate and oral ethinyl estradiol greatly increased SHBG and alpha 2-PAG levels and caused elevated GH and decreased SmC levels. The route of estrogen administration is probably of major importance for the hormonal effects on hepatic activity as reflected by SHBG and alpha 2-PAG levels. Bypassing the portal circulation might be advantageous with respect to liver-related side effects of estrogen therapy. GH and SmC might act as mediators of estrogen effects on the human liver.

Administration, Oral↗

Hormonal regulation of an estramustine-binding protein in the submaxillary gland of the rat.

An estramustine binding protein, in many aspects similar to the prostatic secretion protein (PSP), has partly been characterized in the submaxillary gland of the male rat. The [3H]estramustine-macromolecule complex is found in the void volume of a Sephadex G 200 column, indicating a Stokes radius larger than 52 A. The estramustine binding protein is bound to Concanavalin-A, indicating a glycoprotein structure. Like PSP, the macromolecule complex that is bound to Concanavalin-A inhibits the binding of the androgen-receptor complex to DNA-cellulose. The concentration of the protein is decreased following testectomy or estrogen treatment but can be restored to normal values following testosterone administration. These results strongly indicate that the estramustine binding macromolecule in the submaxillary gland belongs to the same group of proteins as PSP. We have earlier proposed a role for PSP as an intracellular regulator of androgen activity. Based on these new results it is tempting to speculate that androgen sensitive glycoproteins may act in the same way in all androgen sensitive tissues.

Animals↗

Analysis of an estrogen binding macromolecule in human pancreas by radioimmunoassay.

A radioimmunoassay for quantitation of the human pancreatic estrogen binding protein (hEBP) was developed using polyclonal rabbit hEBP antiserum and iodinated purified hEBP. Parallel dose-response curves were obtained when serial dilutions of human serum and of cytosols obtained from human pancreas, prostate and colon were analyzed simultaneously with serial dilutions of purified hEBP standard. Very high levels of hEBP (500-1000 mg/kg wet weight) were found in normal pancreas. High as well as medium levels were found in pancreatic carcinoma tissue and medium values (0.1-1 mg/kg wet weight) in prostate, colon and ovarian tissue. Other tissues and serum from healthy volunteers showed low values, usually below 0.1 mg/kg. When serial dilutions of rat pancreatic cytosol were analyzed in the hEBP assay, [125I]hEBP was displaced by the rat preparation, but the dose-response curves were not parallel to the standard curves, indicating similarity but non-identity between the estrogen binding proteins in human and in rat pancreas.

Animals↗

Mouse monoclonal antibodies against rat estramustine binding protein.

Hybridomas producing antibodies against rat prostatic estramustine binding protein (rEMBP) have been obtained by fusion of spleen lymphocytes from Balb/c mice, immunized with rEMBP, and SP2/0 Ag 14 mouse myeloma cells. Anti-rEMBP IgG producing cultures were identified in a solid phase ELISA using alkaline phosphatase conjugated sheep antimouse IgG. Cultures producing specific antibodies were subcloned and expanded. The produced immunoglobulins were characterized according to interaction with subunits of rEMBP. No interaction was found with [3H]estramustine-human estramustine binding protein. Following development of a radioimmunoassay, tissue distribution of rEMBP in the rat was studied. Despite high specificity, shown by selective interaction with rEMBP (F and S subunits), macromolecules interacting with anti-rEMBP were found in high concentrations in the prostrate and also in low concentrations, in other tissues of the male genital tract, and further in the adrenals, pancreas and submaxillary gland. The high specificity also makes it possible to study the F and S subunit selectively. These results show that macromolecules very similar to rEMBP are present in hormone-sensitive tissues in the rat.

Animals↗

Adrenal steroids in post-menopausal women: relation to obesity and to bone mineral content.

Basal levels and ACTH-induced increments of serum 17 alpha-hydroxyprogesterone (170HP), cortisol, 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), and dehydroepiandrosterone sulphate (DHAS) were related to the degree of obesity and to trabecular bone mineral density in 29 postmenopausal women. The ACTH-induced increment of 170HP (delta 170HP) was negatively correlated to basal DHA and delta DHA. Positive correlations were found between obesity, expressed as Broca's index, and delta DHA and the delta DHA/delta 170HP ratio. Bone mineral density was positively correlated to basal DHAS, delta DHA, delta DHAS and the delta DHA/delta 170HP ratio, and negatively correlated to delta 170HP. DHA and 170HP represent a crossroad in adrenocortical steroid biosynthesis, leading to delta 5-androgens and glucocorticoids as main products. Besides age, obesity may also influence the intra-adrenal distribution between these two main steroidogenic pathways. The results suggest that differences at a very early stage of the adrenal steroidogenesis may influence calcium homeostasis in the post-menopausal woman.

Adrenal Cortex Hormones↗

Orchidectomy or oestrogen treatment in prostatic cancer: effects on serum levels of adrenal androgens and related steroids.

Peripheral serum levels of dehydroepiandrosterone (DHA) and its sulphate (DHAS), 4-androstene-3, 17-dione (A-4), 17 alpha-hydroxyprogesterone (17-OHP), cortisol and albumin were measured in patients with prostatic cancer before treatment and after orchidectomy or during combined oral and intramuscular oestrogen treatment. Orchidectomy caused a pronounced decrease in 17-OHP levels and minor but significant decreases in the levels of A-4 and DHAS. Dehydroepiandrosterone, cortisol and albumin were unaffected by treatment. Oestrogen treatment caused a pronounced decrease in the serum levels of DHA, DHAS, 17-OHP and A-4 and a small but significant decrease in serum albumin. Cortisol levels increased, probably due to elevated transcortin levels. The ratio of DHA to DHAS was unaffected by either orchidectomy or by oestrogen treatment. These results confirm that the testis contributes to circulating DHAS. The mechanism behind the more pronounced decrease in adrenal androgens during oestrogen treatment is not known but, for DHAS, increased metabolic clearance due to the decrease in albumin levels may contribute in this respect. The unchanged values for the ratio of DHA to DHAS indicate that this sex-specific sulphatase/sulphotransferase balance is insensitive to endocrine manipulations in adult men. The results further invalidate the hypothesis that there is a 'compensatory' increase in adrenal androgen output following orchidectomy.

17-alpha-Hydroxyprogesterone↗

Serum prolactin assays have no prognostic value in treatment of prostatic cancer by orchidectomy or estrogens.

Eighty patients (54-75 years) with cytologically and/or histologically confirmed cancer of the prostate (CAP) were randomly allocated to either orchidectomy (ORX, n = 41) or combined intramuscular and oral estrogen treatment (ESTR, n = 39). Serum levels of prolactin (PRL) were determined prior to treatment and 6, 12 and 24 months after initiation of the treatment. In the ORX group, 32 patients responded to the treatment and 9 did not. In the ESTR group, 27 patients responded and 12 did not. Serum PRL levels were significantly increased by ESTR treatment in responders as well as in nonresponders, but were not affected by ORX. There were no differences in PRL values between responders and nonresponders at any time in any of the two treatment groups. It is concluded that serum PRL assays have no prognostic value in the employed endocrine treatment of CAP.

Aged↗

Free testosterone and testosterone/SHBG index in hirsute women: a comparison of diagnostic accuracy.

Serum levels of sex hormone binding globulin (SHBG), total testosterone (T), free testosterone (fT), 4-androstene-3,17-dione (A-4) and dehydroepiandrosterone sulfate (DHAS) were determined in 30 patients with the polycystic ovary syndrome. Subnormal levels of SHBG were found in 60% of the patients. Elevated levels of T were found in 53%, of fT in 53%, of the T/SHBG ratio in 90%, of A-4 in 75% and of DHAS in 36% of the patients. The better diagnostic accuracy of the T/SHBG ratio compared to fT may be explained by the regulatory effect of SHBG binding upon the albumin-bound fraction of T, which may be another biologically active T fraction. It is concluded that the assay of fT does not offer any further diagnostic advance compared to conventional determinations of T. Assays of fT do not provide any information about the origin of the elevated levels of biologically active androgen.

Adult↗

Oestrogen and thyroxine-binding globulin levels in early normal pregnancy.

Peripheral serum levels of thyroxine-binding globulin (TBG), unconjugated and total oestrone, and unconjugated oestradiol-17 beta were measured twice in 60 cases of early normal pregnancy (gestational weeks 6-19). Although highly significant correlations between TBG and oestrogen levels were obtained in the total material, the correlations within two-week intervals of pregnancy were rather poor and mostly insignificant. Furthermore, there were no associations at all between the increase rates of TBG and those of the oestrogens, either within two-week intervals or in the total material. The findings do not support the common concept of continuously rising oestrogen stimulation as the main factor affecting the TBG synthesis during pregnancy.

Estradiol↗

Serum estrogen levels after topic application of estradiol-17 beta on two different cutaneous areas.

Circulating estrogen concentrations were compared in 11 postmenopausal women during 3 months of percutaneous administration of estradiol-17 beta on the skin of the abdomen and on the thigh. The absorption from the two different cutaneous areas was equally effective and the serum levels of estradiol-17 beta were in the same range as previously reported after oral therapy with doses of 2 mg estradiol. In contrast to oral therapy the excessive conversion into estrone was avoided. The medial inner aspect of the thigh could be used as an alternative to abdominal application during percutaneous estrogen therapy.

Abdomen↗

Serum sex hormone binding globulin (SHBG), testosterone/SHBG index, endometrial pathology and bone mineral density in postmenopausal women.

Serum levels of sex hormone binding globulin (SHBG) and testosterone (T) and bone mineral density (BMC) in the non-dominant forearm were determined in 28 postmenopausal women aged 44-62 years. Significant correlations (Spearman's rank correlation test) were found between BMC and SHBG (negative) and between BMC and the T/SHBG index on biologically active androgen (positive). Significant correlations were also found between endometrial pathology (Kruskal-Wallis test; 0 = atrophic, 1 = hyperplasia, 2 = cancer) and SHBG (negative) and the T/SHBG index (positive). It is suggested that SHBG may act as one common denominator in the pathogenesis of postmenopausal osteoporosis and endometrial disease by regulating the levels of unbound, biologically active androgens and estrogens.

Adult↗

Metabolism of estrone sulfate by normal human pancreatic tissue in vitro.

Homogenates of normal pancreatic tissue obtained from five female and nine male subjects transformed (3H)estrone sulfate into (3H)estrone and (3H)estradiol-17 beta in vitro. No other unconjugated (3H)metabolites were found. The rates of transformation were comparable to those previously demonstrated in mammary carcinoma and greatly exceeded those found in endocrinologically unrelated pectoralis and abdominal muscle. The results may provide additional indications for a possible association between estrogens and pancreatic function.

Estradiol↗