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Biomedical subjects

S Edén

Publications and source records attributed to S Edén.

At least 73 records · Page 4Linked to original sources

Altered growth hormone secretion during oral contraception.

Serum profiles of growth hormone (GH) were recorded for 24 h in 9 young healthy women before and during treatment with monophasic, combined contraceptives. During treatment, there was a change in GH secretion towards a pattern of smaller peaks at a higher frequency. The mean peak amplitude decreased from 11.2 to 7.3 mU/l, the mean peak area from 24.1 to 14.1 mU/l, and the mean interpeak interval from 4.3 to 3.0 h. The biological impact of altered GH secretion is well-known from animal experiments. A sex-steroid-induced change in GH secretion may be relevant for certain metabolic effects of oral contraceptives.

Adult↗

Effects of growth hormone and hypophysectomy of pregnant rats on serum concentrations of pregnancy-associated murine protein-1.

Continuous infusion of bovine GH to hypophysectomized non-pregnant rats increased serum concentrations of pregnancy-associated murine protein-1 (PAMP-1) to the levels of adult female rats and pregnant rats. Serum concentrations of PAMP-1 were followed from Day 16 of gestation until 3 days after parturition in hypophysectomized (on Day 14 of gestation) and intact pregnant rats. In the intact pregnant rat there was a decrease in PAMP-1 values from Day 16 until delivery. The serum concentrations of PAMP-1 in hypophysectomized pregnant rats were similar to those in intact pregnant rats before parturition, but PAMP-1 concentrations decreased markedly after parturition in the hypophysectomized rats. We suggest that the serum concentrations of PAMP-1 can be maintained without pituitary GH in late pregnancy, while serum values of PAMP-1 in non-pregnant rats is dependent upon a continuous secretion of pituitary GH.

Animals↗

The plasma pattern of growth hormone in conscious rats during late pregnancy.

The plasma GH levels of female rats during late pregnancy were determined using an automatic method for repetitive blood sampling from conscious animals. The plasma GH patterns were analysed by a pulse analysis computer program (PULSAR). The mean plasma GH levels were about twofold higher in pregnant females on days 15, 18 and 22 of gestation than in age-matched non-pregnant females. The basal plasma GH levels were also increased, while there was no change in GH pulse amplitude or frequency. The augmentation of GH release was even more pronounced on day 20 of gestation, with a fourfold increase in mean plasma GH levels compared with those in non-pregnant females. This increase reflected an increase in both basal plasma GH levels and GH pulse amplitude, but there was no increase in pulse frequency. In female rats that delivered on day 22 of gestation, the basal and mean plasma GH levels increased during parturition. Pregnant females consistently responded to multiple i.v. infusions of 1 microgram human GH-releasing factor analogue (hGRF(1-29)-NH2) given at 45-min intervals on day 18 of gestation. Both basal and GRF analogue-stimulated plasma GH levels were undetectable after hypophysectomy of pregnant rats. The present study demonstrates an increase in basal plasma GH levels during late pregnancy and a marked increase in both basal plasma GH levels and GH pulse amplitude on day 20 of gestation. Furthermore, hypophysectomy of pregnant rats results in undetectable GH levels, indicating that the high levels of GH during pregnancy are derived from the pituitary.

Animals↗

Body composition in acromegaly: the effect of treatment.

Total body water (TBW) and total potassium (TBK) were measured in patients participating in a follow-up investigation of all acromegalic patients seen between 1956 and 1984. The results were compared with population-based estimates of TBK and TBW calculated from height (BH), weight (BW) age and sex, using data from a large number of healthy subjects (n = 476). The findings were compared with values obtained at diagnosis and were also related to growth hormone (GH) and IGF-I/SmC concentrations at follow-up. BW at follow-up was unchanged compared to BW at diagnosis and was 9.7 and 10.0 kg higher in males and females, respectively, than in healthy subjects of the same BH (BWnorm). Growth hormone concentration at follow-up correlated directly with excess extracellular fluid volume (ECW%) (P less than 0.001) and inversely with the ratio observed/predicted body fat (BF%) (P less than 0.001) as well as with BW/BWnorm (P less than 0.05). On the other hand, GH concentration did not correlate with excess body cell mass (BCM%) estimated from TBK. IGF-I/SmC concentration correlated with GH concentration at follow-up (P less than 0.001) and with ECW% (P less than 0.01) but not with BCM% or BF%. In 39 patients, data on body composition were also available at diagnosis. Of these, three males had developed gonadal insufficiency and their BCM had decreased markedly. One patient had suffered from hemiplegia. Five patients had not received any treatment. In the remaining 30 treated patients, those with a post-treatment GH concentration below 5 mU/l were normalized with respect to ECW and BF. BCM, however, was unchanged. In contrast, patients with GH concentration greater than or equal to mU/l displayed unchanged body composition. Furthermore, BH decreased significantly in successfully treated patients.

Acromegaly↗

Body composition in acromegaly.

Total body water (TBW) and potassium (TBK) were measured in untreated acromegalic patients seen between 1956 and 1984 and the results were compared to values predicted from height (BH), weight (BW), age and sex, using data from a large number of healthy subjects (n = 476). Normal body weight for each patient (BWnorm) was predicted from BH and sex, the regression equations being derived from a representative population sample (n = 4017). The BH for each patient was compared with data on BH in 15,000 Swedes. The patients were significantly taller than the control population (P less than 0.001). In 107 (70%) of the 156 patients BH was above the median. Patients with an early onset of the disease were taller than those with a later onset. TBK and TBW were significantly higher than predicted from observed BW (P less than 0.001) and so was the quotient extracellular water (ECW)/intracellular water (ICW). Body fat (BF), on the other hand, was lower than predicted (P less than 0.001). Observed BW in male acromegalics was 8.1 kg higher than predicted from healthy subjects of the same BH (BWnorm), a difference explained by an average increase of 4.7 kg in body cell mass (BCM) (P less than 0.001) and 7.1 kg in extracellular water (P less than 0.001) simultaneously with a mean decrease of 3.7 kg in BF (P less than 0.01). Female acromegalics weighed on average 6.4 kg more than healthy women, a difference explained by an increase in BCM of 3.3 kg (P less than 0.001) and in ECW of 4.6 kg (P less than 0.001) concomitantly with a decrease in BF of 1.5 kg. Mean hGH concentration at diagnosis correlated inversely with the quotients observed/predicted BF (P less than 0.01) and BW/BWnorm (P less than 0.05) but not with the quotients observed/predicted TBK, TBW or ECW/ICW.

Acromegaly↗

Diurnal variations in thyrotropin, prolactin and cortisol during human pregnancy.

Diurnal variations in serum concentrations of thyrotropin (TSH), prolactin (PRL) and cortisol were measured in 4 women during late stages of pregnancy (gestational weeks 34-38), in 2 women at an early stage of pregnancy (gestational weeks 11 and 17) and in 2 nonpregnant women. Blood samples were obtained through a nonthrombogenic catheter using continuous withdrawal of blood by means of a portable pump changing the recipient tube at 30-min intervals. Serum TSH concentrations showed a diurnal variation in both pregnant and nonpregnant women with maximal values around midnight. Serum PRL concentrations were elevated in pregnant women but the concentrations showed marked variations indicating episodic secretion of the hormone. Serum cortisol concentrations increased in pregnant women, but the typical diurnal pattern persisted with nadir levels around midnight and marked elevations during the early morning hours. The results suggest that also during human pregnancy there is a diurnal variation in TSH and cortisol secretion, as well as an episodic secretion of PRL.

Circadian Rhythm↗

Differential effects of continuous versus intermittent administration of growth hormone to hypophysectomized female rats on serum lipoproteins and their apoproteins.

The effects of the plasma pattern of GH on serum and lipoprotein levels of total cholesterol, triglycerides, apolipoprotein A-I (apo A-I), apolipoprotein B 48/100 (apo B), and apolipoprotein E (apo E) were studied in hypophysectomized female Sprague-Dawley rats, which had been given replacement therapy with L-T4 and hydrocortisone. Bovine GH (1 mg/kg.day) was administered sc either continuously by means of osmotic minipumps or by two daily injections. Serum lipoproteins were separated by sequential ultracentrifugation into very low density lipoproteins [density (d) less than 1.006 g/ml], low density lipoproteins (LDL; d 1.006-1.063 g/ml) and high density lipoproteins (HDL; d 1.063-1.21 g/ml). The content of total cholesterol and triglycerides were then determined. Apo A-I, apo B, and apo E were isolated from rat serum and antibodies raised in rabbits. In serum and in lipoprotein fractions, the content of apo A-I, apo-B, and apo E were determined by electroimmunoassay. After hypophysectomy, there occurred a decrease in serum cholesterol and serum levels of apo A-I and apo E, in spite of replacement therapy with T4 and cortisone. Similar changes were also observed in HDL. In contrast, apo B, cholesterol, and triglycerides were increased in LDL. Estradiol treatment had no effect on these changes. Continuous infusion of GH resulted in an increase in cholesterol and apo E in serum and HDL to the levels of intact females. In contrast, GH given twice daily had no effect. Therefore, the sexually dimorphic secretion of GH may be important for the regulation of sex differences in apo E and HDL cholesterol levels. There were no consistent effects of GH treatment on the levels of apo A-I in serum or HDL, but GH treatment resulted in a decrease in apo B and triglycerides in both serum and LDL, regardless of the mode of administration. This suggests that GH regulates the serum and LDL levels of apo B and triglycerides independently of the secretory pattern.

Animals↗

Plasma growth hormone profile in acromegaly before and ten days after transsphenoidal surgery.

Profiles of plasma GH, plasma somatomedin-C and serum PRL concentrations as well as serum GH response to iv TRH were determined in 11 patients with acromegaly before and 10 days after surgery. Blood for profile determinations was drawn from a peripheral vein with a continuous withdrawal pump changing the recipient tube at 30-min intervals. Before surgery all patients had high plasma GH concentrations with irregular peaks and somatomedin-C concentrations were elevated. The response to TRH was abnormal in 8 patients. Three patients had slightly elevated PRL concentrations and one had high PRL concentration (6900 mU/l). Ten days after surgery GH concentrations were still high in 2 patients (greater than 5 mU/l), as were somatomedin-C concentrations (3.2 and 2.4 U/l, respectively). In 3 patients basal GH concentrations were less than 5 mU/l and somatomedin-C concentrations were normal, but there were no major peaks in plasma GH concentrations. In 2 patients major peaks in GH concentrations appeared after surgery, but basal GH concentrations were 1.9 and 0.95 mU/l, respectively. One patient with hyperprolactinemia still had slightly elevated PRL concentration (486 mU/l), but the response to TRH was normalized. Finally, in 4 patients, mean GH concentrations were markedly reduced, somatomedin-C concentrations normalized and apparently normal plasma GH profiles appeared with low or undetectable basal levels separating major peaks. The results indicate that in some patients with acromegaly apparently normal GH secretion can be demonstrated 10 days postoperatively. Characterization of circadian GH rhythms during the early postoperative stage may contribute to the evaluation of the effect of surgery.

Acromegaly↗

Demonstration of growth hormone receptors in cultured rat epiphyseal chondrocytes by specific binding of growth hormone and immunohistochemistry.

Growth hormone has been reported to exert direct effects on rat and rabbit epiphyseal chondrocytes in vitro, indicating that GH interacts with specific receptors on these cells. To investigate this possibility, binding of GH to cultured rat epiphyseal chondrocytes was studied under various experimental conditions. Chondrocytes were isolated enzymatically from epiphyseal growth plates of the proximal tibia of 20-day-old male rats and were cultured in monolayer in Ham's F-12 medium supplemented with 10% calf serum and 1% of a serum substitute. The cells were seeded at various densities (25,000-200,000 cells/well) and cultured for 5-16 days. Twenty-four hours before binding experiments, the medium containing calf serum was changed for one containing serum obtained from hypophysectomized rats, in order to avoid binding of GH present in the calf serum. Binding was studied by incubating 125I-labelled human GH (hGH) with the cells in the presence or absence of various concentrations of unlabelled hGH, bovine GH (bGH), rat GH (rGH) and ovine prolactin (oPRL). Specific binding could be demonstrated in cells cultured for 5-16 days. Binding was dependent upon time and temperature, and maximal binding was obtained by incubating the labelled hormone for 4-6 h at 24 degrees C. An increase in binding was noted between 7 and 12 days in culture. In cells cultured for 12 days, addition of unlabelled hGH, bGH or rGH caused a dose-dependent displacement of 125I-labelled hGH, whereas oPRL was ineffective. Scatchard analysis resulted in a linear plot, and the number of binding sites/cell was approximately 5700, with a dissociation constant of 0.46 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sex differences in fatty acid composition of rat liver phosphatidylcholine are regulated by the plasma pattern of growth hormone.

The effects of continuous and intermittent (at 12 h intervals) administration of growth hormone (GH), and the effects of gonadal steroids on the regulation of the fatty acid composition of liver phosphatidylcholine were studied in gonadectomized and hypophysectomized adult female Sprague-Dawley rats. Gonadal steroids have been shown to influence the fatty acid composition of liver phosphatidylcholine in the rat. It is shown in the present study that neither testosterone nor estradiol had any effects on liver phosphatidylcholine in hypophysectomized rats. There was a 'masculinizing' effect of hypophysectomy of female rats on the fatty acid composition of liver phosphatidylcholine (i.e., an increase in the proportion of palmitic, oleic and linoleic acids and a decrease in the proportion of stearic and arachidonic acids). Continuous infusion of human GH and bovine GH partly reversed the 'masculinizing' effect of hypophysectomy. In contrast, there were no effects of intermittent administration of human GH. Also, there was no effect of prolactin infusion. It is concluded that the sexually dimorphic secretory pattern of GH may be involved in the regulation of the sexual differentiation of the fatty acid composition of liver phosphatidylcholine in the rat.

Animals↗

Epidemiology and long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984.

In 1985, a follow-up investigation was performed of all patients with acromegaly (n = 166, 89 women and 77 men) seen over a 30-year period (1955-1984) at our Endocrine Unit, referral centre for the western region of Sweden (population 1.5 million). At the end of 1984, the prevalence of the disease was 6.9 per 10(5) inhabitants, the average incidence per year was 3.3 per million people. Mean age at diagnosis was 46.3 years and at death (n = 62) 64.1 years. About one-third of the patients (50/153), in whom it had been possible to estimate the total duration of the disease, had survived for more than 25 years. Mortality was, however, increased compared to the normal population. The observed number of deaths from vascular and malignant disorders was 32 and 15, respectively, compared to the expected numbers 9.0 (p less than 0.001) and 5.6 (p less than 0.01).

Acromegaly↗

Plasma pattern of growth hormone regulates sexual differentiation of phosphatidylcholine in rat plasma.

The effects of continuous and intermittent administration of human growth hormone (hGH) in the regulation of plasma phosphatidylcholine fatty acid composition was studied in adult hypophysectomized male and female Sprague-Dawley rats. Human GH was given for 7 days, either continuously by means of Alzet osmotic minipumps implanted s.c. or intermittently by means of s.c. injections at 12-h intervals. The 'masculinizing' effect of hypophysectomy on the fatty acid composition of plasma phosphatidylcholine in female rats, i.e. an increase in the proportions of palmitic and linoleic acids and a decrease in the proportions of stearic and arachidonic acids, was to a large extent reversed by continuous administration of hGH, while intermittent administration had no consistent effect. This effect of continuous hGH administration similar effect of continuous administration of hGH was also observed in hypophysectomized male rats. Prolactin had no effect on the fatty acid composition of phosphatidylcholine. Replacement therapy with thyroid hormones and glucocorticoids had a small effect on the proportions of palmitic and stearic acids in plasma phosphatidylcholine. It is concluded that the more continuous secretory pattern of GH in female rats is involved in the sexual differentiation of the fatty acid composition of plasma phosphatidylcholine.

Animals↗

Secretory pattern of growth hormone regulates plasma concentration of pregnancy-associated murine protein-1 in the non-pregnant rat.

Serum concentrations of pregnancy-associated murine protein-1 (PAMP-1) were followed in hypophysectomized adult female rats during treatment with oestradiol and continuous or intermittent human growth hormone (hGH). After hypophysectomy a rapid decrease in PAMP-1 values was recorded while concentrations of albumin and the acute phase alpha 2-macroglobulin were unaffected. PAMP-1 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 oestrogen replacement treatment had any effect. It is concluded that the serum concentration of PAMP-1 in the non-pregnant rat is regulated by the sexually dimorphic secretory pattern of GH.

Animals↗

Continuous 24-hour secretion of growth hormone during late pregnancy. A regulator of maternal metabolic adjustment?

A dramatic change in growth hormone secretion was demonstrated during the 3rd trimester of human pregnancy, when compared with the non-pregnant state. The pulsatile pattern, with intermittent high peaks, and low or undetectable levels between peaks, characteristic of normal men and non-pregnant women, was completely abolished. All the 10 pregnant women investigated had the same stable basal circulating growth hormone concentration. Values were in the range 6-10 mU/l and there was no evidence of pulsatile activity. Previously, in animal experiments, a continuous secretion of growth hormone has been shown to 'feminize' hepatic steroid metabolism, hepatic prolactin receptors, hepatic sulphatase activity and to stimulate pregnancy protein synthesis. The same biological principle could be valid also during human pregnancy and be related to maternal metabolic adjustment.

Circadian Rhythm↗

Growth hormone secretion during termination of pregnancy. Further evidence of a placental variant.

Serum profiles of growth hormone (GH), hPL and hCG were recorded in 5 pregnant women during termination of pregnancy at cesarean section and legal abortion. Two monoclonal antibodies directed against different epitopes on the GH molecule were used to distinguish the pituitary 22K-GH from the placental GH variant. After placental removal at cesarean section, a rapid fall in GH as well as in hPL and hCG concentrations was recorded. On the other hand GH levels were unaffected when early pregnancy was terminated by legal abortion. The importance of an intact placental function for the maintenance of high GH levels lends further support to the concept that a placental GH variant is produced during late pregnancy.

Abortion, Induced↗

Screening for thyroid disease in the elderly. Serum concentrations of thyrotropin and 3,5,3'-triiodothyronine in a representative population of 79-year-old women and men.

Thyroid function in individuals from a representative population of 79-year-olds was evaluated clinically and from measurements of serum thyrotropin (TSH) and 3,5,3'-triiodothyronine (T3). High TSH concentrations (greater than or equal to 10 mU/l) were found in 16 of 320 women (5%) and 2 of 204 men (1%). Signs and symptoms which traditionally are regarded as related to hypothyroidism were as common in subjects with high TSH concentration as in the remaining population and occurred in 10-50% of the subjects. In the 16 women with high TSH, free thyroxine (free T4) concentrations were low in 10, whereas only one subject had low thyroxine (T4) and T3 concentrations, indicating that free T4 is a more sensitive parameter for thyroid hypofunction in the elderly. Based on the T3 assay, there was no evidence for hyperthyroidism in this population. The results indicate that high TSH concentrations are common in elderly women, less common in men. The results show that classical symptoms of thyroid dysfunction are quite common in 79-year-olds, but do not correlate with biochemical indicators of thyroid dysfunction, indicating that defining "clinically euthyroid" in an elderly may be almost impossible.

Aged↗

The influence of gonadal steroids and the pituitary on the levels and composition of plasma phospholipids in the rat.

Gonadal steroids have been shown to influence plasma phospholipids. In the present study, the possible interaction between gonadal steroids and the pituitary in the regulation of plasma phospholipids was studied in rats. The total phospholipid concentration (higher in females) and the fatty acid composition of plasma lecithin was different in male compared to female rats. Gonadectomy resulted in a "feminization" of plasma phospholipids (total concentration and fatty acids in lecithin) in male rats but had no effect in females. Testosterone treatment of gonadectomized males or intact females resulted in a "masculinization" of plasma phospholipids, whereas estrogen treatment of intact males resulted in a "feminization." Hypophysectomy resulted in a marked decrease in plasma phospholipid concentration and the fatty acid composition of lecithin showed a "masculine" pattern in both males and females. Neither testosterone nor estrogen treatment had any effects on plasma phospholipids in hypophysectomized male and female rats, respectively. It is concluded that gonadal steroids and the hypothalamic-pituitary axis interact in the regulation of the synthetic and perhaps also degradative pathways controlling plasma phospholipids.

Animals↗