Staffan Edén

Cardiovascular and renal effects of growth hormone

OBJECTIVE With the advent of recombinant human GH (rhGH), it has become possible in controlled clinical studies to explore the effects of GH replacement in adults with GH deficiency. The objective of this study was to determine cardiovascular and renal effects of GH replacement in adults with GH deficiency.

Growth hormone 24‐h serum profiles during pregnancy—lack of pulsatility for the secretion of the placental variant

Summary. Serum profiles of growth hormone (GW) were recorded for 24 h in women at different stages of normal pregnancy. Two monoclonal antibodies directcd against different epitopes and unaffected by human placental lactogen were used in radioimmunoassays to distinguish the pituitary 22K‐GH from the placental GH variant. The ‘normal’ episodic peak activity of GH in non‐pregnant and first trimester pregnant women was dramatically changed into a continuous very stable secretion during late pregnancy. This change was first observed at 17 weeks gestation. It is concluded that during the second half of pregnancy, serum measurements of GH reflect a major contribution from a non‐cpisodically secreted placental GH variant and a concomitant suppression of pituitary GH. This specific signal, i.e. a continuous GH secretion, may be an important regulator of maternal liver metabolism during pregnancy.

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<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< 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< 0.001).

Evidence for a Growth Hormone Releasing Factor Mediating Alpha-Adrenergic Influence on Growth Hormone Secretion in the Rat

The effects of adrenergic receptor agonists on GH secretion were studied in adult, male rats pretreated with reserpine and somatostatin antiserum. Frequent blood samples were obtained from intra-aortic cannulae. Plasma GH was determined by radioimmunoassay. Reserpine (10 mg/kg i.p.) caused a complete suppression of the normal, pulsatile secretion of GH in all animals. Administration of somatostatin antiserum resulted in rapid elevations of plasma GH in reserpine-pretreated rats with peak levels at 30 min. GH levels then fell but remained slightly elevated for the duration of the sampling period (8 h). Apomorphine (0.5 mg/kg i.p.) had no effect on plasma GH levels, whereas clonidine (0.5 mg/kg i.p.) induced release of GH in both antiserum treated and control rats. The results indicate that the alpha-adrenergic influence on the secretion of GH is mediated not by inhibition of somatostatin release but rather by effects on the release of a GHRF.

Up- and down-regulation of central postsynaptic α2 receptors reflected in the growth hormone response to clonidine in reserpine-pretreated rats

The α-adrenergic mechanisms exert a stimulatory influence on the secretion of growth hormone (GH) in the rat. In the present study the α receptors involved in GH regulation were characterized with respect to subtype. It was also investigated whether the GH response to α receptor agonists can be utilized to assess changes in the responsiveness of central α receptors. The experiments were performed on rats with implanted intra-aortic cannulae allowing frequent blood sampling from freely moving animals. Plasma GH was determined by radioimmunoassay. Reserpine (10 mg/kg) caused a suppression of the normal pulsatile secretory pattern of GH. The α receptor agonist clonidine (CLON) given to reserpine-pretreated animals induced a dose-dependent increase in plasma GH. The effect of CLON (0.2 mg/kg) was prevented by pretreatment with the α2 receptor antagonist yohimbine (3 mg/kg), but not by the α1 receptor antagonist phenoxybenzamine (10 mg/kg). Chronic pretreatment with CLON or imipramine, either of which can be expected to produce a reduced sensitivity of central α2 receptors, resulted in reduced GH responses to CLON. On the other hand, chronic treatment with yohimbine, which should cause denervation supersensitivity of α2 receptors, led to enhanced GH responses to CLON. The results indicate that GH release in the rat is stimulated by postsynaptic α2 receptors. They also suggest that the GH response to CLON can be used as a valid in vivo model reflecting decreased, as well as increased responsiveness of this type of receptor.

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 < 0.001) and inversely with the ratio observed/predicted body fat (BF%) (P < 0.001) as well as with BW/BWnorm (P < 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<0.001) and with ECW % (P< 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/1 were normalized with respect to ECW and BF. BCM, however, was unchanged. In contrast, patients with GH concentration |Mg 10 mU/1 displayed unchanged body composition. Furthermore, BH decreased significantly in successfully treated patients.

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°C was reached at 120 min and half‐maximal specific binding at 6–8 . Apparent K a was 2.1 × 109 M−1 and B max 7.3 × 10−11 M/106 cells. The human fat cellgrowth 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.

Low dose continuously infused growth hormone results in increased lipoprotein(a) and decreased low density lipoprotein cholesterol concentrations in middle‐aged men

OBJECTIVE Animal studies have shown that slight increases in basal GH concentrations may result in changes in lipoprotein metabolism. Such changes in GH secretion have been observed in physiological and pathophysiological states such as fasting, uncontrolled diabetes and during oestrogen treatment. The aim of this study was to investigate the possible effects of increases in basal plasma GH concentrations on lipoprotein concentrations.

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.

Recombinant human insulin‐like growth factor‐I decreases serum lipoprotein(a) concentrations in normal adult men

OBJECTIVE Lipoproteln(a) is a lipoprotein fraction associated with atherosclerosis. The serum concentration of llpoprotein(a) has been shown to be mainly genetically determined but recently evidence for hormonal regulation has been presented. The aim of the present study was to Investigate the effects of insulin‐like growth factor‐I on serum lipoproteins, especially lipoprotein(a).