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Biomedical subjects

S Edén

Publications and source records attributed to S Edén.

At least 91 records · Page 5Linked to original sources
PubMed1987

Regulation of insulin-like growth factor II receptors by growth hormone and insulin in rat adipocytes.

The acute and long-term effects of growth hormone (GH) on the binding of insulin-like growth factor II (IGF-II) were evaluated in adipose cells from hypophysectomized rats given replacement therapy with thyroxine and hydrocortisone and in cells from their sham-operated littermates. After the cells were incubated with insulin and/or GH, the recycling of IGF-II receptors was metabolically inhibited by treating the cells with KCN. IGF-II binding was 100 +/- 20% higher in cells from GH-deficient animals when compared with sham-operated controls. These GH-deficient cells also showed an increased sensitivity for insulin as compared with control cells (the EC50 for insulin was 0.06 ng/ml in GH-deficient cells and 0.3 ng/ml in control cells). However, the maximal incremental effect of insulin on IGF-II binding was reduced approximately 27% by hypophysectomy. GH added to the incubation medium increased the number of IGF-II binding sites by 100 +/- 18% in cells from hypophysectomized animals. This increase was rapidly induced (t1/2, approximately 10 min), but the time course was slower than that for the stimulatory effect of insulin. Half-maximal effect of GH on IGF-II binding was obtained at approximately equal to 10 ng/ml. Thus, GH added in vitro exerted a rapid insulin-like effect on the number of IGF-II receptors. GH also appears to play a regulating role for maintaining the cellular number of IGF-II receptors and, in addition, modulates the stimulatory effect of insulin on IGF-II binding.

Adipose Tissue↗
PubMed1987

Effects of oestrogen and human growth hormone on pregnancy-associated plasma proteins in the rat.

The serum concentrations of pregnancy-associated murine protein-1 (PAMP-1), acute phase alpha 2-macroglobulin, albumin, transferrin, and complement factor 3(C3) were followed in male rats during continuous infusions of oestradiol-17 beta and human growth hormone. Three different patterns of protein response could be distinguished. A distinct acute phase response without any additive influence of the given hormones was recorded for alpha 2-macroglobulin, whereas the levels of albumin, transferrin and C3 were virtually unaffected throughout the experiment. Growth hormone gave a rapid and pronounced increase of PAMP-1 levels, whereas the response to oestradiol of this 'steroid-sensitive' protein was significantly weaker and delayed. It is suggested that the apparent oestrogenic influence on certain pregnancy-associated plasma proteins is mediated via growth hormone.

Animals↗
PubMed1986

Specific binding of human growth hormone but not insulin-like growth factors by human adipocytes.

Binding of human GH (hGH) and insulin-like growth factors I and II (IGFI and II) to isolated human adipocytes from adult subjects was studied. Binding equilibrium for hGH at 24 degrees C was reached at 120 min and half-maximal specific binding at 6-8 ng/ml. Apparent Ka was 2.1 X 10(9) M-1 and Bmax 7.3 X 10(-11) M/10(6) cells. The human fat cell growth hormone receptor recognized neither bovine, ovine or rat GH nor human prolactin or placental lactogen. No specific receptors for human IGFII could be demonstrated. Thus, human adipocytes do not possess IGF receptors but have specific GH receptors which recognize hGH but not GH from lower species.

Adipose Tissue↗
PubMed1986

Induction of growth hormone (GH) receptors in adipocytes of hypophysectomized rats by GH.

The ability of GH to regulate its own receptor in adipocytes of hormone-substituted hypophysectomized rats was studied. Male rats (130-150 g) were hypophysectomized and substituted with T4 and cortisone. A fixed dose of GH (bovine GH, human GH, or ovine GH), was administered for 5-6 days in three different ways: 1) two injections/day, 2) four injections/day, or 3) by osmotic minipumps. GH binding was measured in cell aliquots using [125I]human GH. In unsubstituted hypophysectomized animals, GH binding was decreased and was approximately 25% of the binding observed in adipocytes of normal rats. With T4 and cortisone replacement, GH binding was partially restored. When GH was administered in four daily injections or via osmotic minipumps, a further increase in GH binding was observed. This increase was observed if the animals were killed up to 6 h but not 12 h after the last GH injection. GH given in two daily injections had no effect on GH binding even when studied at different time periods after the last GH injection. The GH receptor induced by frequent or continuous administration of GH was mainly somatogenic, since an excess of unlabeled ovine PRL inhibited GH binding only to a minor extent. There was no difference in accumulated body weight gain between the GH-treated groups during the treatment period. The results show that GH regulates its own receptor in adipocytes and that the mode of administration of the hormone is of importance for this effect of GH.

Adipose Tissue↗
PubMed1985

Changes in growth hormone binding and metabolic effects of growth hormone in rat adipocytes following hypophysectomy.

Growth hormone (GH) binding and the effect of GH and insulin on glucose metabolism in rat adipocytes were studied at various time periods following hypophysectomy. Male rats were hypophysectomized at 33-34 days of age. After 6 h, 20 h or 3, 7 and 14 days adipocytes were prepared from epididymal fat pads by mild collagenase digestion (0.5 mg X ml-1, 60 min, 37 degrees C). Glucose metabolism was studied by determining the production of CO2 from [14C]glucose and the incorporation of [14C]glucose into lipids. GH binding was measured in cell aliquots using [125I]hGH. No difference in GH binding to adipocytes was observed between control rats and rats hypophysectomized or sham-operated 6 h earlier. GH binding was significantly decreased 20 h after hypophysectomy and declined further with time after hypophysectomy. Adipose tissue from normal rats is usually refractory to the insulin-like effect of GH. Adipocytes isolated from normal rats were, however, usually responsive to GH immediately after cell isolation, suggesting that refractoriness to the insulin-like effect of GH was lost during the time required for the preparation of adipocytes. The magnitude of the response to GH in adipocytes progressively declined with time after hypophysectomy. The decreased responsiveness to GH with time after hypophysectomy parallelled the decrease in GH binding. The results suggest that the pituitary, directly or indirectly, is necessary for the maintenance of GH binding sites in adipose tissue and that these binding sites are related to the insulin-like effect of GH.

Adipose Tissue↗
PubMed1985

Mode of action of pituitary growth hormone on target cells.

Normal postnatal somatic growth becomes progressively dependent on GH with time. In contrast to other hormones, GH is the only hormone known to produce a dose-dependent stimulation of postnatal growth. Most of the effects attributed to GH action appear to be the result of a direct effect of GH on cells in different peripheral tissues, including cartilage. In addition to the growth-stimulating effect, GH has the intrinsic properties of being able to exert both insulin-like and insulin-antagonistic effects in adipose tissue and skeletal muscle. These two apparently antagonistic effects seem to be explained by the stage of responsiveness of the target cells to GH, which is determined by the previous influence of endogenous GH. An inhibition of adenylate cyclase with a concomitant decrease in intracellular cAMP might be an important early cellular event in the course of GH action, but it is not known whether or how this change in nucleotide metabolism relates to the various expressed effects of the hormone. The recognition that GH directly interacts with chondrocytes in cartilage suggests that alterations in the concentration of circulating somatomedins cannot be the only factor regulating skeletal growth. The recent discovery by Green and coworkers (42) demonstrating that GH specifically stimulates the differentiation of cloned preadipose cells and myoblasts in tissue culture may be a major breakthrough in the understanding of the mechanism of action of the growth-promoting effect of GH. Green (42) has proposed that GH directly stimulates terminal differentiation of cells in many different tissues including epiphyseal plate cartilage. The finding that GH binds specifically to cells in the resting cell zone but not to differentiated chondrocytes in the growth plate suggests that prechondrocytes in the growth plate are the target cells for GH action. If it is correct that GH directly stimulates the differentiation of prechondrocytes, we suggest that, during the process of chondrocyte differentiation in the growth plate, the genes that code for growth factors of the somatomedin class, such as IGF-I, are expressed. As a consequence, the clonal expansion of the chondrocytes in the proliferative zone of the growth plate that occurs in vivo during the process of normal growth is the result of this local production of growth factors.

Animals↗
PubMed1985

Effects of hypophysectomy and GH administration on bovine and human GH binding to rat liver membranes.

Experiments were conducted to investigate the specific binding of highly purified bovine and human growth hormones (bGH and hGH) to purified liver plasma membranes of male rats at various times after hypophysectomy and after the acute intravenous administration of bGH. Liver membranes prepared from hypophysectomized male rats showed a two- to threefold increase in the specific binding of either [125I]iodo-bGH or [125I]iodo-hGH, when compared with membranes prepared from the livers of age-matched normal male rats. The increase in GH binding was apparent within 3 days after hypophysectomy and persisted for a number of weeks after the operation. The increase in GH binding produced by hypophysectomy appeared to be due to an increase in the number of binding sites present on the membranes. The intravenous injection of 200 micrograms of bGH into hypophysectomized male rats 5-60 min before they were killed markedly reduced the ability of liver membranes prepared from these animals to bind [125I]iodo-bGH specifically. This decrease in GH binding seen after the injection of bGH may have been due to the development of a slowly dissociating hormone-binding site complex, which thereby reduced the number of available binding sites. This conclusion is supported by the finding that bGH, which is bound in vitro to isolated liver membranes, dissociates slowly and incompletely in the presence of an excess of unlabeled hormone. Moreover, the degree to which the bound hormone can dissociate appears to depend on the length of time that association is allowed to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Sexual dimorphism in the control of growth hormone secretion.

The secretory pattern of GH in the mature rat is sexually differentiated. In male rats GH is secreted in pulses occurring at regular 3- to 4-h intervals. In females the pulses are lower and plasma GH levels between the pulses are higher than in males. The continuous presence of testosterone appears to be necessary to maintain low basal GH levels in adult male rats. Neonatal, but not prepubertal, gonadectomy decreases GH pulse height in adult male rats to female levels. Administration of testosterone neonatally to castrated animals returns GH pulse height to normal suggesting that neonatal testicular androgen secretion is one determinant for GH pulse height in adult male rats. Administration of testosterone neonatally or during adult life to neonatally ovariectomized rats also produces higher GH pulses. In contrast to testosterone, estrogens elevate basal plasma GH levels and suppress the GH pulses under some conditions. Estrogens may stimulate basal GH secretion by acting directly on the pituitary. The physiological significance of the secretory pattern of GH has been investigated in hypophysectomized rats by simulating different plasma patterns of GH. The results suggest that high, infrequent GH pulses with low plasma GH levels in between (i.e. a masculine plasma GH pattern) promotes growth more effectively than an intermediate, rather constant level of plasma GH (i.e. a feminine plasma GH pattern). Since male sex steroids masculinize the secretory pattern of GH and have only minor growth-promoting effects in hypophysectomized animals it appears that the growth promoting effect of androgens is indirect and is due to an altered secretory pattern of GH. Presumably, neonatal androgen secretion stimulates body growth during adult life by irreversibly masculinizing the secretory pattern of GH. In contrast, estrogens appear to influence body growth by mechanisms that are mainly independent of the secretory pattern of GH. Evidence is accumulating that the secretory pattern of GH in the rat also affects various sexually differentiated hepatic characteristics such as steroid metabolism and prolactin receptor concentration. Thus, a feminization of the liver develops after continuous, but not intermittent, administration of GH to hypophysectomized rats. GH secretion is predominantly regulated by two hypothalamic peptides; GRF, and the GH-release-inhibiting factor, somatostatin.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗
PubMed1985

Effect of insulin treatment of hypophysectomized rats on adipose tissue responsiveness to insulin and growth hormone.

The effects of insulin treatment and dietary glucose on the responsiveness of adipose tissue to insulin and GH after hypophysectomy were studied. Male rats, 130-150 g, were hypophysectomized. Glucose metabolism was measured by determining the production of CO2 from [14C]glucose and the incorporation of glucose into lipids in the epididymal fat pad. Basal levels of glucose oxidation as well as the response to insulin were markedly decreased 7 days after hypophysectomy. In hypophysectomized animals given drinking water containing 10% glucose, insulin responsiveness was partially restored, and an enhanced response to the insulin-like effect of GH was observed. Plasma insulin levels decreased after hypophysectomy. Additional glucose caused a significant increase in plasma insulin levels, but these levels were still lower than those in sham-operated animals. To examine the possibility that endogenous insulin levels are important for the capacity of adipose tissue to metabolize glucose and respond to insulin and GH, hypophysectomized rats were injected with different, progressively increasing doses of insulin for 7 days, beginning on the day after the operation. Basal levels of glucose oxidation were decreased in hypophysectomized control animals and gradually increased in a dose-dependent manner in insulin-treated animals. Basal levels were normalized when the total dose of insulin injected was 16.5 U. In these animals, the response to insulin was enhanced, and there was an increase in the magnitude of the response to GH. Similar results were obtained when glucose incorporation into lipids was determined. The decrease in basal and insulin-stimulated glucose oxidation levels after hypophysectomy were most pronounced when measured at a high glucose concentration (50 mM), when glucose transport is not rate limiting. The results indicate that the changes in glucose metabolism and hormonal responsiveness of adipose tissue after hypophysectomy are, at least in part, dependent upon the decrease in endogenous insulin levels.

Adipose Tissue↗
PubMed1985

Effect of human growth hormone on proteoglycan synthesis in cultured rat chondrocytes.

We have previously demonstrated that hGH stimulates DNA synthesis in cultured chondrocytes in the absence of serum. The present study is concerned with the effects of hGH on proteoglycan synthesis by cultured chondrocytes. Chondrocytes were isolated from rat rib growth cartilage by collagenase digestion, plated in plastic dishes, transferred to serum-free MCDB 104 medium, and incubated for 24 h to establish growth arrest. The cultures were then preincubated for 0-24 h with various concentrations of hGH and ovine prolactin (oPrl) and finally pulse-labelled for 30 min with radioactive sulphate in the presence of hormone. hGH, but not oPrl, stimulated sulphate incorporation with an apparent maximum at 50 ng/ml (approximately 170%). The stimulatory effect was apparent after 2 h and maximal after 3h preincubation. After 12 h the stimulatory effect had decreased to insignificant levels. Qualitative analysis of isolated proteoglycans indicated that the stimulation of sulphate incorporation by hGH is exerted at the level of protein synthesis with little effect on glycosylation and sulphation. Further experiments are required to demonstrate whether the stimulatory effect on proteoglycan synthesis is a specific phenomenon or represents one aspect of a general stimulation on cell metabolism in preparation for DNA synthesis.

Animals↗
PubMed1985

Hormonal regulation of growth hormone binding and responsiveness in adipose tissue and adipocytes of hypophysectomized rats.

The hormonal regulation of GH binding and the effects of GH on glucose metabolism were studied in hypophysectomized rats. Male rats (130-140 g) were hypophysectomized and on the day after the operation treatment with one or a combination of two hormones was started and continued for 7 days. The different hormonal treatments were cortisone acetate, insulin, insulin plus cortisone acetate, thyroxine, thyroxine plus cortisone acetate and GH. Glucose metabolism was studied by determining the production of CO2 from [14C]glucose in epididymal fat pads and adipocytes and the incorporation of [14C]glucose into lipids in adipocytes. Binding of GH was measured in cell aliquots using 125I-labelled human GH. In hypophysectomized control animals, GH binding was decreased to approximately 25% of the binding observed in adipocytes of normal rats. Insulin treatment increased GH binding by approximately 100% and the response to GH was markedly increased. Similar effects were achieved by thyroxine treatment. Basal levels of glucose oxidation were markedly decreased after hypophysectomy but were increased towards normal by insulin or thyroxine treatment. Neither cortisone nor GH treatment had any effect on GH binding or glucose metabolism. The results show that insulin and thyroxine may be important for the GH receptor and the insulin-like effect of GH in adipocytes.

Adipose Tissue↗
PubMed1984

Thyroregulatory changes associated with smoking in 70-year-old men.

In a previous study we have analysed serum free T4 concentrations in a representative population of 70-year-old men. In the present study the effect of previous or present tobacco smoking on free T4, T4, T3, rT3, TSH and thyroid hormone binding proteins was analysed in 181 of the 460 men, excluding those with past or present goitre, those who were obviously ill or had died between 70 and 75 years of age and those who had any disease or medication influencing free T4 concentrations. Smokers had higher T4 and rT3 levels, and lower TSH levels but T3 levels no different from non-smokers. The difference in T4 levels, but not rT3 or TSH levels, between smokers and non-smokers could be attributed to differences in body mass and also to differences in TBG levels. The results indicate that tobacco smoking is associated with long-term alterations in thyroregulatory function.

Aged↗
PubMed1984

Influence of gonadal steroids on age- and sex-related secretory patterns of growth hormone in the rat.

The influence of sex steroids on the pulsatile GH-secretory pattern was investigated in male and female rats of different ages. Neonatal and prepubertal gonadectomy was performed when the rats were 0-1 and 25 days old, respectively. Determinations of plasma GH levels were made in blood samples obtained from the tip of the tail or from a chronic intracardiac venous cannula. After blood sampling from the tip of the tail, maximum and minimum plasma GH levels were determined in individual rats in order to evaluate pulse height and baseline plasma GH levels. In the chronically cannulated rats the GH pulse height and plasma GH baseline levels in individual rats were determined by means of a pulse analysis computer program. Neonatal gonadectomy of male and female rats did not affect the increase in plasma GH that is observed during late prepubertal life in both sexes. However, the pulsatile, sexually differentiated, secretory pattern of GH seen in sexually mature male and female rats was modulated by gonadectomy. In adult male rats, GH was secreted in regular episodes at 3- to 4-h intervals, baseline levels being low or undetectable. After neonatal or prepubertal gonadectomy, GH baseline levels increased in comparison to the sham-operated controls. Replacement therapy with testosterone completely reversed this effect, indicating that a continuous presence of testosterone is necessary for maintaining the low baseline GH levels in adult male rats. Neonatal, but not prepubertal, gonadectomy decreased GH pulse height in male rats during adult life, suggesting that neonatal androgen secretion is a determinant for the pulse height in adult male rats. In female rats, GH pulse height was lower and baseline levels were higher than in male rats. Neonatal gonadectomy resulted in higher plasma GH pulses during puberty and decreased GH baseline levels postpubertally. There were no apparent differences in the GH-secretory patterns between male and female rats after neonatal gonadectomy. Neonatal gonadectomy of male rats decreased body weight gain as well as longitudinal bone growth, as measured in the proximal tibia by the tetracycline method. In contrast, neonatal gonadectomy of female rats resulted in a stimulation of body weight gain and longitudinal bone growth. The present results demonstrate that gonadal steroids influence GH secretion in the rat. We suggest that the sexual differentiation of the GH secretory pattern may be important for the difference in body growth between male and female rats.

Age Factors↗
PubMed1984

Interrelationships among body mass, thyrotropin, thyroid hormones, and thyroid-hormone binding proteins in healthy 70-year-old men.

In a previous study of a representative population of 460 men of age 70, we found that the free thyroxin (free T4) concentration was negatively correlated to body mass. In the present study we analyzed other indicators of thyroid function in relation to body mass and body mass index in 181 individuals without any disease or medication influencing thyroidal homeostasis or body mass. There was a significant negative relationship between body mass and body mass index and free T4, total T4, and 3,3',5'-triiodothyronine (rT3). Thus, individuals with high body mass normally had lower circulating concentrations of these hormones than lean individuals, whereas there was no such relationship for thyrotropin or 3,5,3'-triiodothyronine (T3). The thyroid-hormone binding proteins (thyroxin-binding globulin, prealbumin, and albumin) did not correlate with body mass or body mass index. As expected, thyroxin-binding globulin correlated with T4, T3, and rT3, but not with free T4 or thyrotropin. Concentrations of serum albumin correlated with T3 and rT3 concentrations but not with free T4, T4, or thyrotropin concentrations. Thyrotropin concentrations correlated negatively with free T4, T4, and rT3, but not with T3, indicating that circulating T4 plays the dominant role in feedback regulation of thyrotropin in healthy individuals.

Aged↗
PubMed1983

Regulation of sexually dimorphic hepatic steroid metabolism by the somatostatin-growth hormone axis.

Lesions in the periventricular hypothalamic area in male rats results in a "feminization" of steroid metabolizing enzymes in the liver. These lesions also resulted in a decrease of somatostatin levels in the median eminence. Since blockade of somatostatin by in vivo administration of an antiserum also caused "feminization" of the liver, it is possible that at least one hypothalmic factor responsible for "feminization" is related to somatostatin. Also extrahypothalmic areas seem to influence sexually differentiated functions in the liver. The neuroendocrine control of the "feminizing factor" secretion from the pituitary bears several resemblances to the central control of GH. The hypothesis that the plasma pattern of GH regulates hepatic steroid metabolism in the rat was studied in two different animal models: (1) Different plasma patterns of GH were achieved by administration of human GH (hGH) at different frequencies or by infusing the hormone continuously by means of Alzet osmotic minipumps to hypophysectomized female rats. (2) The plasma pattern of GH in animals with an intact pituitary gland was investigated under conditions which lead to "feminization" of hepatic steroid metabolism. The results demonstrate that the plasma pattern of GH influences hepatic steroid metabolism. Increased trough plasma GH values or absence of time periods with undetectable plasma levels of GH appears to be a major determinant for "feminization" of hepatic steroid metabolism. Since sex steroids were found to influence the plasma pattern of GH it seems as if differences in the plasma pattern of GH between male and female rats explain the sex-differentiated hepatic steroid metabolism.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1983

Factors influencing serum free T4 in 70-year-old men. Implications for reference intervals in the elderly.

We tested a procedure to obtain reference values based on careful clinical analysis of a population sample with the background (a) that there are conflicting reports of age effects on thyroid function parameters, possibly reflecting differences in numbers of sick and drug-treated subjects in the studied populations, and (b) that recommended procedures for the selection of reference subjects in elderly populations may give unacceptably high exclusion rates. Serum free T4 was determined by a ligand-analogue technique in a representative population of 460 males at age 70. The determinations were performed 5 years after the clinical study, and the results were analysed in relation to information obtained at the study as well as during a 5-year follow-up. The free T4 concentration was significantly low in subjects with neoplastic disease and subjects with chronic bronchitis and significantly high in subjects taking non-selective beta-adrenergic blockers. Selective beta 1-blockers had no apparent effect. Information on death during the 5 years after the study proved to have no significance. The free T4 concentration was found to be negatively correlated to body mass and body mass index, a correlation which has previously not been shown. Smoking was associated with a significantly low body mass but had no apparent effect on mean free T4 concentration. A procedure with successive exclusions of clinically defined diagnostic groups with significantly low or high analyte concentration and/or body mass may be used to obtain reference values for thyroid function and may reveal previously unknown relationships.

Adrenergic beta-Antagonists↗
PubMed1983

Sites of action of testosterone and estradiol on longitudinal bone growth.

In this study the mechanisms by which sex steroids influence body growth were investigated. The effect of different doses of testosterone propionate on longitudinal bone growth and body weight gain was studied in a) gonadectomized male rats, b) gonadohypophysectomized male rats, and c) gonadohypophysectomized male rats given replacement therapy with bovine growth hormone (bGH). The effect of different doses of estradiol benzoate on the same growth parameters was studied in female rats divided into the same experimental groups as the males. Accumulated longitudinal bone growth was determined using oxytetracycline as an intravital marker. Testosterone caused a dose-dependent increase in longitudinal bone growth in gonadectomized male rats. In contrast, testosterone exerted no significant increase in longitudinal bone growth in gonadohypophysectomized male rats with and without bGH replacement therapy. Treatment with estrogen inhibited longitudinal bone growth and body weight gain. The inhibitory effect of estradiol was approximately the same in gonadohypophysectomized female rats given bGH replacement therapy as in gonadectomized female rats. The results suggest that testosterone exerts its stimulatory effect on body growth mainly by modulating hypothalamopituitary functions, e.g., by altering the secretory pattern of GH. On the other hand, it seems that changes in the hypothalamopituitary functions are less significant for the inhibitory effect of estradiol on body growth. It is concluded from this study that the sites of action for estrogen and testosterone in modulating body growth in the rat are different.

Aging↗