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Biomedical subjects

K Carlström

Publications and source records attributed to K Carlström.

At least 145 records · Page 8Linked to original sources

On the regulation of sex-hormone-binding globulin--a challenge of an old dogma and outlines of an alternative mechanism.

In this review, the different factors known to affect SHBG levels are discussed with respect to their possible significance in the physiological regulation of this protein: Sex steroids, puberty, nutritional status, thyroid hormones and liver disease. It is concluded that the serum levels of SHBG are related to general metabolic factors, nutritional status, growth and ageing than to the estrogen/androgen balance. The authors suggest that SHBG is regulated primarily by growth hormone, somatomedin-C and possibly other growth factors. Growth hormone may promote SHBG synthesis in the liver while somatomedin-C may stimulate its extravasation and uptake in target tissues. It is suggested that sex steroids merely have an indirect, modulating influence.

Female↗

Secretory pattern of growth hormone regulates steroid sulfatase activity in rat liver.

Steroid sulfatase activity was quantified in liver microsomes from hypophysectomized adult female rats treated with estradiol and continuous or intermittent human growth hormone (hGH). Hypophysectomy clearly enhanced sulfatase activity as compared to intact female rats. Normal female values were completely restored by continuous infusion of hGH (1.4 i.u./kg/day). Neither the same dose of hGH given as two daily injections nor estrogen replacement therapy had any effect. It is concluded that liver microsome sulfatase activity in the non-pregnant rat is regulated by the sexually dimorphic secretory pattern of GH.

Animals↗

Dehydroepiandrosterone sulfate in postmenopausal women: lack of influence of parity.

Serum concentrations of dehydroepiandrosterone sulfate (DHAS) were analyzed in 251 healthy, medicine-free postmenopausal women 46-65 years of age. Twentyfour of the women were nulliparous and 227 parous (1- to 7-parous). There was no association, whatsoever, between parity and DHAS levels. The data are at variance with previous findings in menstruating women of higher DHAS levels in nulliparous than in parous women. This difference between menstruating and postmenopausal women may reflect an influence of age per se on DHAS metabolism. It may also reflect the exclusion in this study of women with i.e. endometrial hyperplasia/cancer, diseases often associated with elevated DHAS levels and increased risk for nulliparous women.

Aged↗

Scheduled intermittent periods of in vitro fertilization treatments.

Organization and results of an in vitro fertilization program at the Huddinge University Hospital are given from its beginning in August 1985: 6 months in advance a scheme is scheduled with 2 weeks open for treatment followed by free intervals of 3-4 weeks. Follicular development is stimulated with clomiphene citrate and hMG, and assessed by analyses of estradiol and LH in serum combined with ultrasound examinations. Following the administration of hCG, eggs are collected by transvesical aspiration guided by ultrasound. The ova are inseminated with about 50,000 motile spermatozoa, and cultured for 48 h. Up to four eggs are transferred transcervically to the uterine cavity. 158 egg pickups have been performed (August 1985 to December 1987) in 106 patients resulting in fourteen intrauterine and two ectopic pregnancies, biochemical pregnancies not counted. This protocol has restricted routine work load allowing these treatments to be part of the clinical routine. It has also allowed the application of research programs and thus optimized limited resources.

Adult↗

Influence of the maturity of the vaginal epithelium upon the absorption of vaginally administered estradiol-17 beta and progesterone in postmenopausal women.

Serum concentrations of estradiol-17 beta and its metabolites estrone (unconjugated) and total estrone (mainly estrone sulfate) and of progesterone were measured before and after application of one vaginal suppository containing 250 micrograms estradiol-17 beta and 10 mg progesterone to 10 previously unsubstituted healthy postmenopausal women with normal pretreatment serum steroid levels. Vaginal hormone cytology was performed prior to administration of the estrogen-progesterone combination. An atrophic vaginal mucosa was found in 5 and a moderate proliferation in the other 5 women. A significant association was found between proliferation and pretreatment values of estrone, but not with other steroids. There was a clear, significant association between steroid absorption kinetics and the condition of the vaginal mucosa as indicated by cytological data: significantly higher absorption was found in women with an atrophic vaginal mucosa.

Absorption↗

Endocrine regulation of cytochrome P-450 in the rat brain and pituitary gland.

In an effort to understand the physiological functions of cytochrome P-450 in the central nervous system and pituitary gland, we evaluated changes in the level of the enzyme as a function of the endocrine status of rats and the ability of these tissues to synthesize or degrade steroids. The P-450 content of microsomes prepared from the hypothalamic preoptic area (HPOA), the olfactory lobes and the cerebrum was 0.040 +/- 0.009 and in the pituitary gland 2.2 +/- 0.6 (S.D.) nmol/g tissue. The P-450 content of the HPOA and olfactory lobes, but not of the rest of the cerebrum, was influenced by the endocrine status of rats. In microsomes it increased five- to tenfold over control levels during late pregnancy in the olfactory lobes and during lactation in the HPOA, and in both brain regions treatment of rats with 5 alpha-dihydrotestosterone (DHT) caused an eight- to tenfold increase in the P-450 content. Androstenedione was not a good substrate for brain P-450. The level of androstenedione 19-hydroxylase in the olfactory lobe microsomal fraction was 0.50 +/- 0.06 nmol 19-hydroxyandrostenedione formed/g tissue per h. This activity was tenfold lower in other brain areas and was not detectable in the pituitary gland. The rate of aromatization of androstenedione to oestradiol in the HPOA and olfactory lobe of lactating rats was 0.46 +/- 0.14 and 0.38 +/- 0.05 pmol/oestradiol formed/g tissue per h respectively. 5 alpha-Androstane-3 beta,17 beta-diol (A-5 alpha-3 beta,17 beta-diol) was a much better substrate for P-450 throughout the brain and pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

5-alpha-Dihydroprogesterone↗

Pancreas-specific protein. New serum marker for graft rejection in pancreas-transplant recipients.

A radioimmunoassay for a novel human pancreatic protein (pancreas-specific protein, PASP) has been developed. We studied the possibility that serum PASP levels reflect pancreas-graft rejections in human pancreas-transplant recipients. Ten patients subjected to combined pancreas-kidney transplantation and 4 patients subjected to pancreas transplantation alone were studied. Twelve kidney recipients served as control subjects. On several occasions, PASP levels were elevated at kidney rejections in patients with combined pancreas-kidney grafts and then decreased after antirejection therapy, although no other indications for concomitant pancreas-graft rejection were at hand. In the recipients of pancreas grafts alone, PASP levels increased before or at the same time as graft rejections were indicated by current methods. In two cases of chronic graft rejection, PASP rose to high levels long before hyperglycemia occurred. In the control group of kidney-graft recipients, PASP levels were stable and were not affected by high serum creatinine levels, kidney-rejection episodes, or antirejection therapy. This study indicates that PASP may be a good serum marker for pancreas-graft rejection.

Adult↗

A novel assay for pancreatic cellular damage: III. Use of a pancreas-specific protein as a marker of pancreatic graft dysfunction in humans.

Pancreas-specific protein (PASP) is a recently isolated and partially characterized major protein in the human pancreas. It has not been described previously. Serum levels of PASP and amylase were analyzed in 21 patients subjected to combined renal and segmental pancreatic transplantation with both organs obtained from the same donor and in eight kidney transplant patients. In the pancreas transplant patients, PASP and amylase levels were elevated in episodes of graft pancreatitis. With chronic graft rejection, PASP rose to high levels long before other indications. In episodes of renal rejection, the levels of PASP, but not always of amylase, were elevated on several occasions. They decreased after antirejection therapy. This may indicate accompanying pancreatic graft rejection. PASP and amylase levels were stable in kidney transplant patients and were not affected by serum creatinine levels, renal rejection, or antirejection therapy. The results support earlier observations that renal rejection in combined pancreas and renal transplant patients may or may not be accompanied by a rejection process in the pancreatic graft. PASP may be the means by which to tell when the pancreatic graft is involved.

Adult↗

Prognostic value of serum hormone concentrations in prostatic cancer.

Seventy-eight patients with cytologically and/or histologically confirmed prostatic cancer were randomly allocated to orchidectomy (ORX, n = 37) or combined intramuscular and oral estrogen treatment (ESTR, n = 41). Serum levels of testosterone (T), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, total estrone (tE1; sum of unconjugated and conjugated estrone, greater than or equal to 85% estrone sulfate), cortisol, luteinizing hormone, follicle-stimulating hormone, prolactin, growth hormone, sex hormone-binding globulin (SHBG), and albumin were determined prior to treatment and 12, 24, and 36 months after initiation of treatment. Fifty patients responded to treatment or had stable disease, and 28 did not respond (12 in the ORX and 16 in the ESTR group). There was no association between pretreatment hormone or protein levels and outcome of the treatment, neither in the total material nor within either of the two treatment subgroups. Significantly higher pretreatment levels of cortisol and prolactin and significantly lower levels of T, tE1, and albumin and a significantly lower T/SHBG-ratio (index on biologically active T) were found in patients with metastatic disease, compared with the patients without metastases. There was no association between testicular or adrenal androgens, SHBG, T/SHBG, and albumin values during treatment and the clinical outcome. The differences found between metastatic and nonmetastatic disease probably simply reflect the more stressful and catabolic condition and generally poorer health in patients with disseminated malignant disease. Furthermore, the study does not lend any support to the hypothesis that indicates an important role of adrenal "rest androgen" in prostatic cancer tumor growth.

17-alpha-Hydroxyprogesterone↗

Cardiovascular follow-up of patients with prostatic cancer treated with single-drug polyestradiol phosphate.

Thirty-eight patients with cancer of the prostate were treated with strict parenteral estrogen in the form of monthly polyestradiol phosphate injections--160 mg, 240 mg, and 320 mg--in this nonrandomized study. In contrast to studies with oral estrogens, there have been no cardiovascular complications at a mean follow-up of 12.9 +/- 0.7 months (SEM). Twenty-nine of the 38 patients (76%) have responded to therapy.

Aged↗

Effects of estrogen and growth hormone on steroid sulfatase activity and estrogen binding in rat liver.

It is now well established that the activity of certain liver enzymes displays sex differences and that administration of human growth hormone to male rats alters the liver metabolism in a "female" direction. In this work we studied steroid sulfatase activity and binding of estradiol-17 beta in livers from intact rats and found a sex difference, with considerably higher enzyme activity in male as compared to female liver tissue. Continuous infusion of native and recombinant human growth hormone and estradiol-17 beta to male rats reduced sulfatase activity to "female" levels. A specific binding of estradiol-17 beta with receptor properties was found in the rat livers, but the concentration of binding sites did not change after administration of growth hormone or estradiol in this group of intact animals. Our data confirm previous reports that continuous administration of human growth hormone "feminize" liver metabolism, and since estradiol was found to have an identical effect on sulfatase activity it is suggested that the effect of estradiol-17 beta in this respect may be indirect, mediated via an altered secretory pattern of rat growth hormone.

Animals↗

The estrogen binding protein in human pancreas: concentrations in subcellular fractions of normal pancreatic tissue, in duodenal juice during pancreatic stimulation and in peripheral serum in normal and pathological conditions.

The steroid binding properties of the human pancreatic estrogen binding protein (hEBP) in cytosol were studied by equilibrium dialysis. A high ligand specificity of the protein was revealed. hEBP in cytosol binds unconjugated steroid estrogens with a medium affinity (Kd = 10(-7) M) but does not bind conjugated estrogens or unconjugated androgens, gestagens, glucocorticoids or cholesterol. Quantitation of hEBP by radioimmunoassay in subcellular fractions of human pancreatic tissue indicated that the protein is translocated into different subcellular compartments. Duodenal juice taken from patients following stimulation of pancreatic secretion by food ingestion (Lund's test) showed high hEBP concentrations, and the levels of hEBP changed concomitantly with the levels of pancreatic isoamylase, indicating that hEBP secretion was stimulated by food ingestion. The levels of hEBP in peripheral serum from healthy subjects showed no sex difference, but were positively correlated to age. Highly elevated (10-20-fold) hEBP levels were found in serum from patients with acute pancreatitis, while normal serum hEBP values were found in other abdominal diseases. It is speculated that hEBP might have a specific role in the transport of estrogens from the peripheral circulation via the pancreas to the duodenum. The elevated hEBP levels in patients with acute pancreatitis indicate that this protein may be used as a marker of cellular damage in the pancreas.

Carrier Proteins↗

Dehydroepiandrosterone sulphate and dehydroepiandrosterone in serum: differences related to age and sex.

Serum concentrations of dehydroepiandrosterone sulphate (DHAS) were determined in 590 healthy women aged 20-87 yr. Simultaneous assays of dehydroepiandrosterone (DHA) were performed in 417 of the women. DHA and DHAS levels correlated negatively with age while the DHA/DHAS ratio proved to be unrelated to age. When values for 60 healthy men in the age range 20-84 yr were compared with those obtained in 60 randomly-selected healthy women who were exactly age-matched, the DHAS levels were found to be significantly lower and the DHA/DHAS ratios significantly higher in the women. These results might be of use in establishing normal clinical ranges for serum DHA, DHAS and the DHA/DHAS ratio in women.

Adult↗

Serum levels of oestrogens, progesterone, follicle-stimulating hormone and sex-hormone-binding globulin during simultaneous vaginal administration of 17 beta-oestradiol and progesterone in the pre- and post-menopause.

Serum concentrations of 17 beta-oestradiol (E2), unconjugated oestrone (E1), total oestrone (tE1), progesterone (P), follicle-stimulating hormone (FSH) and sex-hormone-binding globulin (SHBG) were measured before and after daily intravaginal administration of 250 micrograms micronized E2 and 10 mg micronized P for 14 days to 12 post-menopausal and for 1 day only (during cycle days 5-8) to 11 pre-menopausal women. In the post-menopausal women the levels of all steroids increased to maximum values on day 1, 8-10 h after administration and fell thereafter. In the pre-menopausal women the steroid concentrations rose slowly to a plateau level 10-15 h after administration. Significantly higher absorption of E2 and E1 (area under the curve increments) was noted in the post-menopausal than in the pre-menopausal women. In the post-menopausal women the steroid levels measured on days 7 and 14 corresponded to those observed in the very early or late luteal phase. Area under the curve increments were usually smaller on days 7 and 14 than on day 1 and the absorption kinetics altered to a 'pre-menopausal' pattern. FSH levels were significantly reduced as from 12 h after administration on day 1 and onwards. A slight (10%) but significant increase in SHBG levels was noted on day 14. It was concluded that the combined E2 and P treatment used in this investigation brings about a physiological response with only minimal side effects on the liver as judged from changes in SHBG concentrations.

Administration, Intravaginal↗

Metabolism of estrone sulfate in endometriotic tissue and in uterine endometrium in proliferative and secretory cycle phase.

The metabolism of [3H]estrone sulfate (E1S) into [3H]estrone (E1) and [3H]estradiol-17 beta (E2) was studied in samples of endometriotic tissue and uterine endometrium obtained simultaneously from 13 patients, 7 in the proliferative and 5 in the secretory cycle phase, and 1 menstruating. E1S was efficiently converted into E1 and E2 by both types of tissue. Total hydrolysis (formation of E1 + E2), as well as the specific formation of E2, was higher in uterine endometrium than in endometriotic tissue, especially in the proliferative phase. Cycle phase associated variations in E2 formation occurred in both tissues, but were statistically significant only for uterine endometrium. E2 formation and total hydrolysis were correlated in endometriotic tissue, but not in uterine endometrium, indicating certain differences in the regulation of estrogen metabolism.

Endometriosis↗

A novel serum assay for pancreatic cellular damage. II. High tissue specificity of a pancreatic protein.

A previously unknown major protein in human pancreatic cytosol has been purified and partly characterized. The protein, designated pancreas specific protein (PASP), has a molecular weight of 44,500 and a pI of 6.9. A two-dimensional gel separation technique revealed the protein to be specific for normal pancreatic tissue. Antibodies against PASP were raised in rabbits and a radioimmunoassay was developed for the quantitation of this protein. The following concentrations of PASP (mg/kg wet weight) were found in human tissues: normal pancreas 100-1,000; pancreatic carcinoma 0.1-20; prostate 0.5-5; and 13 other tissues less than 0.5. The levels of PASP in peripheral serum were less than 0.1 mg/L in normal subjects, 0.7-3 mg/L in cases of acute pancreatitis, and less than 0.1 mg/L in cases of pancreatic carcinoma, prostatic diseases, and other abdominal diseases investigated. The high tissue specificity and the specific elevation of serum PASP levels in acute pancreatitis may indicate a use of this protein as a marker of this pancreatic condition.

Biomarkers↗

Hormone levels in male ice hockey players during a 26-hour cup tournament.

Pituitary, adrenal and testicular hormones and steroid-binding proteins were analysed in 15 active ice hockey players and in 16 spectators, matched for physical fitness, during a 26-h cup tournament including three matches. Diurnal variations were noted for all compounds except FSH and SHBG. The levels of cortisol, dehydroepiandrosterone (DHA), 4-androstene-3, 17-dione (A-4) and prolactin increased in players but not in spectators following the matches played in the afternoons, but not following the match played in the morning. Albumin and DHA sulphate (DHAS) levels increased in players following all three matches and SHBG levels increased slightly in players following the afternoon matches, all probably due to haemoconcentration. DHAS and albumin showed simultaneous diurnal variations with a nadir in the morning. 17 alpha-hydroxyprogesterone (17-OHP) and total and non-SHBG-bound testosterone showed similar diurnal patterns in spectators, with maximum levels in the morning. Levels of 17-OHP were largely unaffected by physical stress, while the morning maximum for total and non-SHBG-bound testosterone was completely abolished in players. Minor or insignificant changes were noted for LH and FSH. While the changes in unconjugated adrenal steroids (cortisol, DHA and A-4) reflect changes in acute ACTH stimulation, changes in albumin binding may be more important for the short-term variations in levels of DHAS. The influence of physical stress upon the pattern of testosterone may be mediated mainly by inhibition of testicular steroidogenesis by elevated cortisol and/or prolactin levels, rather than by decreased gonadotrophic stimulation or by alterations in binding to SHBG.

17-alpha-Hydroxyprogesterone↗

Ciclosporin-associated hypertrichosis is not related to sex hormone levels following renal transplantation.

To study a possible relationship between ciclosporin-induced hypertrichosis and sex hormone pattern, the hair growth in different areas of the body was graded and hormone levels were assayed before and up to 6 months after kidney transplantation. Increased hair growth was observed in 100% (23/23) of the patients in skin areas connected with androgen action and in 78% of the patients in androgen-insensitive areas. After renal transplantation the pituitary, testicular and adrenal hormone levels normalized. The posttransplantation levels of these hormones would not explain the observation of increased hairgrowth. Thus, ciclosporin induces hypertrichosis via a mechanism independent of sex hormones.

Adult↗