bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for secondary 5α-reductase deficiency in genital and supra-pubic skin of subjects with androgen insensitivity syndrome
Authors: Wilson S. C. , Oakey R. E. , Scott J. S.
Published: December 2008

Abstract. The activity of 5 in genital and supra-pubic skin (homogenate or fibroblasts) from subjects with complete or incomplete androgen insensitivity syndrome was low compared with mean activity in samples from normally differentiated male controls. Also, in two subjects with incomplete androgen insensitivity syndrome the ratio of the concentration of testosterone to that of 5α-dihydrotestosterone in plasma was raised after hCG stimulation but normal under basal conditions. In three subjects with complete androgen insensitivity syndrome there was no evidence of raised ratios of testosterone to 5α-dihydrotestosterone in plasma under basal or hCG-stimulated conditions. The activities of other steroid metabolizing enzymes, e.g. 17β-hypdroxysteroid dehydrogenase, 3α/β-hydroxysteroid dehydrogenase, were not decreased. The low 5α-reductase activity of androgen insensitive subjects reported here, and by others, may imply that this enzyme in genital skin is in some way androgen dependent, or responsive to other factors associated with androgen insensitivity syndrome.
Endocrine responses to acute stress in castrated rams: no increase in oxytocin but evidence for an inverse relationship between cortisol and vasopressin
Authors: Parrott R. F. , Thornton S. N. , Robinson J. E.
Published: December 2008

Abstract. Plasma concentrations of cortisol, oxytocin, vasopressin and prolactin were measured by radioimmunoassay in eight castrated rams subjected to handling (control), restraint or isolation. Determinations were also made of hematocrit and plasma osmolality. Blood was collected by jugular venipuncture 60 and less than 1 rnin before, and 5, 15, 30, 60 and 120 min after the start of treatment. Plasma cortisol was raised above pre-treatment levels during isolation and restraint but only transiently after handling. In the first 30 min of treatment, cortisol concentrations were higher following isolation than after restraint or handling and, in the final 60 min, levels were higher during both isolation and restraint than after handling. Oxytocin concentrations showed little change but vasopressin levels were reduced 15, 30 and 60 min after the start of isolation and were negatively correlated with those of cortisol. Plasma prolactin concentrations decreased during handling and restraint but remained unaltered after isolation. Osmolality and hematocrit decreased in all three treatment conditions. These findings indicate that stress does not alter oxytocin levels in sheep, but changes in vasopressin secretion and water balance may occur if cortisol release is greatly enhanced.
Vasoactive intestinal peptide stimulates gonadotropin-releasing hormone release from rat hypothalamus in vitro
Authors: Ohtsuka Shirou , Miyake Akira , Nishizaki Takamichi , Tasaka Keiichi , Tanizawa Osamu
Published: December 2008

Abstract. The effects of vasoactive intestinal peptide (VIP) on the releases of LH and GnRH were examined in a sequential double chamber perifusion system by perifusing the medio-basal hypothalamus and/or pituitary excised from normal female rats in diestrus or ovariectomized rats. When the medio-basal hypothalamus and pituitary from normal rats in series were perifused with VIP (10−6 mol/l), the concentration of LH in the efflux was increased by 59–181% above that before the injection (P < 0.05), VIP having a dosedependent effect. VIP had no effect on LH release from the pituitary perifused alone. Infusion of VIP at 10−6 mol/l induced a significant release (84–159% increase, P < 0.05) of GnRH from the medio-basal hypothalamus. Infusion of 10−6 mol/l VIP induced a significant release (41–99% increase, P < 0.05) of LH in ovariectomized rats. These findings suggest that VIP induces GnRH release from the medio-basal hypothalamus, resulting in LH release from the pituitary, and that this process does not require ovarian estrogen.
Intermediary metabolism, insulin sensitivity and insulin receptor status under comparable long-term therapy with insulin injections and continuous subcutaneous insulin infusion
Authors: Marshall S. M. , Taylor R. , Home P. D. , Alberti K. G. M. M.
Published: December 2008

Abstract. We have compared metabolic parameters, insulin sensitivity and insulin receptor status in 12 patients with insulin-dependent diabetes after 6 months treatment with insulin injection therapy and continuous subcutaneous insulin infusion therapy (CSII) in random order. Mean 24-h blood glucose, intermediary metabolite, plasma free insulin and counter-regulatory hormone concentrations were equivalent on the two regimes despite a significantly lower insulin dose on CSII (49.8 ± 4.0 vs 39.3 ± 2.2 U/24 h, P < 0.01). When compared with a group of matched normal subjects, mean blood glucose and M-value, blood 3-hydroxybutyrate and free insulin concentrations were significantly higher on both regimes whilst blood alanine levels were depressed. Peripheral insulin sensitivity as assessed by the euglycemic clamp, basal hepatic glucose output, glucose carbon recycling, adipocyte insulin binding, adipocyte insulin sensitivity and lipogenesis were all similar after the two treatments. Insulin-stimulated initial rates of glucose uptake by adipocytes were higher after CSII (1.78 ± 0.16 vs 2.35 ± 0.27 pmol per cm2 cell membrane per 20 sec, P < 0.005).
Receptors for insulin-like growth factor-I in plasma membranes isolated from bovine mesenteric arteries
Authors: Bornfeldt Karin E. , Arnqvist Hans J. , Dahlkvist Hans H. , Skottner Anna , Wikberg Jarl E. S.
Published: December 2008

Abstract. Binding of IGF-I to plasma membranes from bovine mesenteric arteries was studied. The maximal specific binding of IGF-I was found to be 7.4 ± 1.7% of total 125I-IGF-I added to the incubation medium. Unlabelled IGF-I displaced 125I-IGF-I with an IC50 value of 0.5 nmol/l and a maximal displacement of 64.2 ± 2.8% of total binding. The potency of insulin to displace 125I-IGF-I was 100–1000-fold lower. Crosslinking of 125I-IGF-I to the receptor with disuccinimidyl suberate, followed by SDS-polyacrylamide gel electrophoresis under reducing conditions showed an IGF-I binding protein with a molecular weight of 146000 Dalton. In summary, we have shown the presence of receptors for IGF-I in plasma membranes isolated from macrovessels. The binding characteristics and the size of the binding unit were found to be similar to those of the IGF-1 receptor found in cultured vascular smooth muscle cells. Furthermore, insulin at high concentrations was found to interact with the IGF-I receptor.
Inhibition of 5α-reductase activity in prepubertal female rats: effect on the timing of first ovulation
Authors: Uilenbroek J. Th. J. , Woutersen P. J. A.
Published: December 2008

Abstract. The activity of 5α-reductase in the ovary of prepubertal rats decreases prior to first ovulation. To determine whether this decrease causes the onset of first ovulation, prepubertal female were treated with a specific inhibitor of 5α-reductase activity and the effect on the time of first ovulation was studied. The steroid (6-methylene-progesterone, MEP) gives irreversible inhibition of ovarian 5α-reductase activity in vitro with testosterone as well as progesterone as substrate. A MEP-containing silicone tube, releasing 245 nmol per 24 h in vitro, was implanted sc in the back of 25-day-old female rats. This resulted a day 30 in a significantly lower 5α-reductase activity in the ovary than in control rats (42.0 ± 3.8 pmol/min per mg ovary in MEP-treated rats vs 98.8 ± 2.4 pmol/min per mg ovary in control rats). Nearly the same extent of inhibiton was found at day 35 27.4 ± 2.1 in MEP-treated rats vs 56.2 ± 5.9 in control rats). However, implantation of a MEP-containing silicone tube under the skin or inserting a pellet containing MEP under the ovarian capsule did not result in advancement of the first ovulation. These data indicate that in the female rat a decrease of 5α-reductase activity alone is not sufficient to induce the first ovulation.
The synthetic human growth hormone fragment (32–38) increases glucose uptake in the conscious dog
Authors: Stevenson Ralph W. , Stebbing Nowell , Jones Theodore , Carr Keith , Jones Peter M. , Hii Charles , Cherrington Alan D.
Published: December 2008

Abstract. hGH32-38 was tested to determine if the peptide could affect hepatic glucose production in the conscious dog under basal conditions (euglycemia) or if it could enhance glucose uptake when hyperglycemia was induced. hGH32-38 (1.6 nmol · kg−1 · min−1) or vehicle was infused in a cross-over design study into each of 4 conscious 16 h-fasted dogs for 3 h (0–180 min) following a 40 min control period. At 90 min, plasma glucose was raised to and maintained at 9.4 mmol/l by glucose infusion for 3 h (until 270 min). Neither hGH32-38 nor vehicle infusion had a significant effect on insulin and glucagon levels or on tracer determined ([3-3H]glucose) glucose production. As a result, neither treatment changed plasma glucose (5.72 ± 0.17 to 5.78 ± 0.17 mmol/l with hGH32-38; 5.50 ± 0.22 to 5.50 ± 0.17 mmol/l with vehicle). Induction of hyperglycemia (9.4 mmol/l) caused glucagon concentrations to fall similarly to about 50 ng/l with and without hGH32-38. Insulin rose to similar levels in both protocols, yet more glucose was required to maintain the same hyperglycemia with hGH32-38 (135– 180 min) (74.9 ± 12.7 vs 43.7 ± 7.1 μmol · kg−1 · min−1, P < 0.05). In summary, hGH32-38 significantly increased glucose disposition during hyperglycemia and this effect may be attributed to enhanced insulin action or to an insulin independent action of the peptide.
A technique for superfusion of isolated granulosa cells. Dynamics of cAMP production and steroidogenesis in response to gonadotropins
Authors: Johanson Carl , Johanson Viktor
Published: December 2008

Abstract. A superfusion model for isolated ovarian cells was developed and characterized in detail. Granulosa cells isolated from pre-ovulatory rat ovarian follicles were placed in superfusion (perifusion) chambers with a volume of 125 μl. Culture medium was pumped through the chambers, collected in 20-min fractions of 600 μl and analysed for cAMP and steroids. Viability was confirmed by morphological examination. The use of polycarbonate membranes to retain the cells in the chambers was abandoned since the membranes caused severe cell damage. The temporal relationships between gonadotropic stimuli and the release of cyclic 3':5'-adenosine monophosphate (cAMP) and steroids was investigated. Within 10 min FSH elicited transient increase in the release of cAMP and progesterone but had no effect on testosterone or estradiol-17β release. Amplitude and duration of the response in cAMP and progesterone release were correlated to concentration and length of the FSH pulse when these parameters were varied within the ranges 1–100 μg/l and 30–270 min, respectively. Compared with the cAMP response, the progesterone response peaked up to 30 min later and lasted 1 to 2 h longer but could not be extended to more than approximately 6 h, not even with longer FSH pulses. These results could indicate a development of desensitization.
Differential effects of cisterna magna cannulation on β-endorphin levels in rat plasma and cerebrospinal fluid
Authors: Barna I. , Sweep C. G.J. , Veldhuis H. D. , Wiegant V. M.
Published: December 2008

Abstract. The concentration of β-endorphin-like immunoreactivity (β-ELIR) was determined in plasma and cerebrospinal fluid (CSF) of rats at various times following the implantation under Hypnorm® anesthesia of a permanent cannula into the cisterna magna. Plasma β-ELIR levels were highly increased immediately after the operation, and gradually returned to basal within 6 h. The β-ELIR concentration in CSF followed a completely different pattern. It appeared to be rather stable during the first hour after the operation, was decreased at 2 h, and showed a marked increase 24 h after surgery. Two days after the surgery, β-ELIR levels in CSF had decreased to a stable basal level which was maintained for at least 7 days. When at this stage animals were treated with Hypnorm, plasma β-ELIR was again highly increased 30 min and not 24 h after injection, but no changes were found in the β-ELIR concentration in CSF. These data indicate that implantation of a cannula into the cisterna magna induces postoperative changes in the CSF levels of β-endorphin that are detectable up to at least 24 h later. Moreover, the lack of correlation between CSF and plasma levels of β-ELIR points towards differences in the regulation of brain and pituitary pro-opiomelanocortin cells.
Osmolality-regulated arginine vasopressin release in conscious dogs. Evidence for dopaminergic or opioid modulation?
Authors: Hellebrekers L. J. , Lagerweij E. , de Vries H. W. , Van Wimersma Greidanus Tj. B.
Published: December 2008

Abstract. Experiments were performed in conscious dogs, in order to study the possibility of dopaminergic or opioid modulation of the osmolality-regulated release of AVP. Hypertonic saline (20%), infused during a period of 2 h at a rate of 0.03 ml· kg−1 · min−1, induced a significant AVP response, which was not influenced by prior administration of bromocriptine or naloxone. Data presented in this report, therefore, are not in support of a dopaminergic or opioid modulation of the osmolality-regulated AVP release in dogs. The results demonstrate a great consistency in individual plasma osmolality-plasma AVP relationships, next to a large inter-individual variation.
Cholecystokinin-33 potentiates and vasoactive intestinal polypeptide inhibits gastric inhibitory polypeptide – induced insulin secretion in the perfused rat pancreas
Authors: Sandberg E. , Ahrén B. , Tendler D. , Efendic S.
Published: December 2008

Abstract. Gastric inhibitory polypeptide (GIP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) stimulate insulin secretion. In this study we investigated whether CCK-33 and VIP could influence the insulinogenic effect of simultaneously administered GIP and 6.7 mmol/l glucose in the perfused rat pancreas. We found that at 0.1 nmol/l, GIP markedly potentiated glucose-induced insulin release whereas CCK-33 and VIP had a weak stimulatory effect and only during the late phase. At this low dose level, CCK-33 potentiated but VIP inhibited the late phase of insulin release stimulated by glucose and GIP. At 1.0 nmol/l, GIP, CCK-33, and VIP markedly potentiated both phases of glucose-induced insulin secretion. At this dose level CCK-33 and GIP exerted additive stimulatory effects on the late phase of insulin release triggered by glucose. In contrast, 1.0 nmol/l VIP inhibited insulin secretion augmented by glucose and GIP. In summary 1) GIP, CCK-33 and VIP all potentiate glucose-induced insulin secretion from the perfused rat pancreas, and 2) CCK-33 potentiates and VIP inhibits GIP-induced insulin secretion. We suggest that interactions of this kind are of importance for the precise regulation of insulin secretion.
Opioid-mediated inhibition of oxytocin during insulin-induced hypoglycemic stimulation of vasopressin in man
Authors: Seckl J. R. , Haddock J. A. , Dunne M. J. , Lightman S. L.
Published: December 2008

Abstract. We have investigated the importance of endogenous opioids in the differential control of neurohypophysial peptide secretion. The effect of the opioid antagonist naloxone on the vasopressin and oxytocin responses to insulin-induced hypoglycemia was studied in 14 male subjects. Either saline (N = 8) or naloxone (4 mg bolus + 6 mg/h, N = 6) was infused iv during the study. After 60 min infusion soluble insulin 0.15 U/kg was injected. Naloxone infusion for 60 min did not alter basal plasma AVP or OT levels. Insulininduced hypoglycemia led to a significant rise in plasma AVP in both saline and naloxone-infused subjects (P < 0.05), which was maximal 45 min after insulin. There was no significant difference in the plasma AVP response to hypoglycemia between the 2 groups. Salineinfused subjects did not show any change in plasma OT in response to hypoglycemia whilst during concurrent naloxone infusion there was a significant rise in OT from 1.9 ± 0.4 pmol/l before insulin to 3.2 ± 1.3 pmol/l at 45 min (P < 0.05). We conclude that there is opioidmediated inhibition of OT which prevents its release when AVP is secreted in response to insulin-induced hypoglycemia.
Augmentation of glucose induced insulin secretion by pertussis vaccine, phentolamine and benextramine: involvement of mechanisms additional to prevention of the inhibitory actions of catecholamines in rats
Authors: Smith Maureen , Furman Brian L.
Published: December 2008

Abstract. Pertussis vaccine, pertussis toxin, and the α-adrenoceptor blocking drug phentolamine augment glucose-induced insulin secretion. The present study was carried out to determine the relationship between this action and the ability of these agents to prevent the inhibitory actions of adrenaline. Pertussis vaccine augmented glucose-induced insulin secretion in rat islets ex vivo and prevented the inhibitory actions of adrenaline and clonidine. Incubation of islets with phentolamine or the irreversible α-adrenoceptor blocking agent benextramine also augmented glucose-induced insulin secretion. However, the α-adrenoceptor blocking drugs idazoxan, yohimbine or phenoxybenzamine, in concentrations that prevented the inhibitory effects of adrenaline and/or clonidine, did not modify glucose-induced insulin release in vitro. Benextramine (1 × 10−5 mol/l) blocked the inhibitory effect of clonidine, whilst having no significant effect on the response to adrenaline. It is concluded that stimulation of insulin secretion by certain α-adrenoceptor blocking drugs can be dissociated from their α-adrenoceptor properties. The ability of pertussis vaccine, phentolamine or benextramine to augment glucose-induced insulin release in vitro is unlikely to be due to the prevention of the inhibitory action of endogenous catecholamines.
Levels of α-subunits of gonadotropins can be increased in Zollinger-Ellison syndrome, both in patients with malignant tumours and with apparently benign disease
Authors: Bardram Linda , Agner Tove , Hagen Claus
Published: December 2008

Abstract. To evaluate the value of intact hCG, the β-subunit of hCG and the common α-subunit of the glycoprotein hormones as tumour markers in patients with gastrinomas, we investigated 30 patients with the Zollinger-Ellison syndrome. Fifty-seven percent of the patients with malignant disease (N = 7) and 45% of those with active and apparently benign disease (N = 20) had raised values of circulating α-subunit. Detectable levels of hCG or hCG-β were found in 7 patients of whom 4 had malignant disease. Radical tumour resection in 2 patients resulted in normalisation of elevated levels of β-subunit, and in one patient who developed metastases, the α-subunit values became elevated simultaneously. By chromatographic studies we found that the α-subunit-like reacting substance in serum eluted as the normal free α-subunit in 8 patients, but in one patient with metastatic disease we found evidence for production of a larger molecular form of α-subunit. The results indicate that the common α-subunit is a valuable tumour marker in patients with gastrinomas, whereas hCG-β is only seldomly elevated. Single estimates of any of the hormonal fragments seem not to relate with malignancy, whereas a rise in α-subunit concentration in some patients may be related to the development of malignancy.
Atrial natriuretic factor during exercise in patients with congestive heart failure
Authors: Keller Niels , Larsen John , Sykulski Roman , Storm Tommy , Thamsborg Gorm
Published: December 2008

Abstract. In order to evaluate the potential relationship between atrial pressure development and release of atrial natriuretic factor (ANF), 33 patients with congestive heart failure were investigated with rightsided heart catheterization during supine graded bicycle exercise. Resting plasma ANF levels were higher in patients with heart failure as compared with normal controls, 75.1 ± 45.6 pmol/l vs 12.3 ± 6.2 pmol/l (mean ± sd, N = 33 and N = 42, respectively) and correlated with right atrial, pulmonary arterial and pulmonary capillary wedge pressures. During exercise, central pressures rose steeply with a simultaneous increase in plasma ANF in all patients. Plasma ANF levels correlated with heart rate at a workload of 25 w, to pulmonary arterial and pulmonary capillary wedge pressure at 50 w, and to pulmonary capillary wedge pressure at 75 w. The increments in ANF levels between the different workloads during exercise did not correlate with the corresponding increments in pressure values. In congestive heart failure, the capability of ANF secretion in consequence to pressure stimuli is preserved, and left atrial pressure seems to be the major stimulus for ANF release during exercise.
Corticosteroid-induced stimulation of atrial natriuretic peptide in man
Authors: Saxenhofer Hermann , Angst Martin , Weidmann Peter , Shaw Sidney G. , Ferrier Claudia
Published: December 2008

Abstract. Previously, we reported elevated plasma immunoreactive ANP (irANP) levels from the 2nd to the 9th day of administering either prednisone, 50 mg/day, or 9α-fludrocortisone acetate (9αF), 0.6 mg/day, to normal humans. To investigate the course of plasma irANP levels during the first 48 h of corticosteroid adminstration, 9 healthy men (mean age ± sem, 24 ± 1 years) received in randomised sequence A) a 4-h iv infusion of prednisolone sodium tetrahydrophthalate followed by oral administration of prednisone for 2 days; or B) a 4-h infusion of aldosterone followed by oral administration of 9αF for 2 days. Basal supine plasma irANP levels averaged 32 ± 5 ng/l in study A and 30 ± 6 ng/l in study B; they were unchanged or even deceased up to 24 h of glucocorticoid or mineralocorticoid administration, but rose (P < 0.01) to 56 ± 9 and 62 ± 12 ng/l at 48 h, respectively, of the two interventions. During glucocorticoid treatment, blood pressure (BP) and indices of the sodium-fluid volume state were unchanged after 48 h. During 9αF administration, body weight increased (1.1 ± 0.3%, P < 0.001), whereas urinary sodium excretion (63 ±7%, P < 0.001), hematocrit (4.1 ± 1.1%, P < 0.001), and plasma renin activity (38 ± 4%, P < 0.001) decreased. Conclusions: The increase in circulating irANP at 48 h of administration of either a glucocorticoid or a mineralocorticoid demonstrates a distinct but slow response of the ANP system to these corticosteroids in normal humans. ANP may play a potential role in mediating and/or modulating physiological and pathophysiological effects of corticosteroids.
Theophylline prevents the inhibitory effect of prostaglandin E 2 on glucose-induced insulin secretion in man
Authors: Giugliano D. , Cozzolino D. , Salvatore T. , Giunta R. , Torella R.
Published: December 2008

Abstract. This study was undertaken to assess the mechanism by which prostaglandins of the E series inhibit glucose-induced insulin secretion in man. Acute insulin response (mean change 3–10 min) to iv glucose (0.33 g/kg) was decreased by 40% during the infusion of prostaglandin E2 (10 μg/min) and glucose disappearance rates were reduced (P < 0.05). Insulin response to arginine (5 g iv) and tolbutamide (1 g iv) were not affected by the same rate of prostaglandin E2 infusion. The inhibitory effect of prostaglandin E2 on glucoseinduced insulin secretion was prevented by theophylline (100 mg as a loading dose followed by a 5 mg/min infusion), a drug that increases the intracellular cAMP concentrations by inhibiting phosphodiesterase activity. Our data suggest the involvement of the adenylate cyclase system in the inhibitory action of prostaglandin E2 on glucose-induced insulin secretion in man.
Effects of fasting on blood plasma levels, metabolism and metabolic effects of epinephrine and norepinephrine in steers
Authors: Fröhli Daniel , Blum Jürg W.
Published: December 2008

Abstract. Experiments were designed to study effects of 3 days of fasting on blood plasma levels, metabolic clearance rates (MCR) and effects of norepinephrine (NE) and epinephrine (E) on levels of glucose, nonesterified fatty acids (NEFA) and immunoreactive insulin (IRI) in 12 steers. During fasting, levels of E, NE and protein did not change, whereas IRI, T3 and glucose decreased and NEFA, acetoacetate and β-hydroxybutyrate increased. Before and at the end of fasting, NE or E were iv infused for 120 min. NE and E were elevated after 15 min and to the end of the infusion. The increase in E, but not in NE, was significantly greater after 3 days of fasting than before fasting (P < 0.05). MCR for E was lower after fasting (299 ± 17 vs 204 ± 10 ml·kg−0.75·min−1; P < 0.001), whereas MCR for NE was not significantly different (455 ± 37 vs 400 ±27 ml·kg−0.75·min−1). MCR was higher for NE than for E, both before and after fasting (P < 0.05). After the infusions, E and NE decreased within minutes to pre-infusion concentrations. During E infusions, NEFA increased significantly more, whereas glucose increased less in fasted than in fed animals. During NE infusions, NEFA increased in fasted, but not in fed animals, and glucose increased less at the end than before fasting. IRI decreased during E infusions only in fed animals, and transiently increased after the infusion, except after NE infusion in fasted steers. Changes in plasma levels, clearance rates and sensitivity to effects of NE and E, together with alterations of insulin and T3 concentrations, may contribute to shifts in energy metabolism during food restriction.
Direct stimulatory effect of growth hormone on DNA synthesis of fetal chicken osteoblasts in culture
Authors: Slootweg M. C. , van Buul-Offers S. C. , Herrmann-Erlee M. P. M. , Duursma S. A.
Published: December 2008

Abstract. GH action on cartilage is thought to be mainly mediated through the somatomedins produced by the liver. However, recent studies using cultured chondrocytes also point to a direct mitogenic action of GH. Besides, a direct action of GH on fetal rat tibiae has been demonstrated. This study is the first to show stimulation of thymidine uptake as well as DNA synthesis under the influence of physiological concentrations of human and chicken GH in fetal chicken osteoblasts in culture.
Serum levels of the low molecular weight form of insulin-like growth factor binding protein in healthy subjects and patients with growth hormone deficiency, acromegaly and anorexia nervosa
Authors: Hall Kerstin , Lundin Gunnel , Póvoa Guilherme
Published: December 2008

Abstract. The low molecular weight form of insulin-like growth factor binding protein (35 kD IGFBP), determined in serum by radioimmunoassay during non-fasting conditions, was high at birth and declined with increasing age during childhood and adolescence (N = 149). Inverse correlation was found between chronological age and 35 kD IGFBP values (r = −0.61, P < 0.001) during childhood and adolescence, but no age dependency was found in adult subjects aged 20–66 years (N = 73). The mean and 95% confidence limits of immunoreactive 35 kD IGFBP were 34 μg/l and 15–79 μg/l, respectively, in healthy adults (N = 73) in whom the blood samples were drawn after a one-night fast. The mean level of the 35 kD IGFBP in patients with acromegaly (19 μg/l, N = 23) was decreased by 50% in comparison with healthy adults, whereas a 2-fold elevation of the mean levels was found in both anorexia nervosa patients (70 μg/l, N = 13) and adult patients with GH deficiency (69 μg/l, N = 22). In patients with anorexia nervosa, the 35 kD IGFBP levels were inversely related to the body mass index (r = −0.65, P < 0.02).
Adenosine and the regional differences in adipose tissue metabolism in women
Authors: Stoneham Susanna , Kiviluoto Tuula , Keso Leila , Ohisalo Jorma J.
Published: December 2008

Abstract. Adenosine content in abdominal and femoral adipose tissue in menstruating women was 0.38 ± 0.10 and 0.59 ± 0.14 nmol/g of wet weight, respectively (mean ± sem; N = 17). No difference in adenosine sensitivity was found between abdominal and femoral adipocytes. In lactating women, the adenosine content was lower in femoral than in abdominal adipose tissue (0.40 ± 0.08 and 0.57 ± 0.08 nmol/g of wet weight, respectively; N = 10). Adenosine sensitivity in femoral adipocytes was not increased during lactation. As adenosine is a locally acting insulin-like effector, these results suggest that the higher adenosine content in femoral adipose tissue in menstruating women could explain its higher lipoprotein lipase activity and tendency to accumulate fat. During lactation, the lower extracellular adenosine concentration would allow lipid mobilization preferentially from the femoral site.
ACTH deficiency, hyperprolactinemia and benign intracranial hypertension
Authors: Aanderud Sylvi , Jorde Rolf
Published: December 2008

Abstract. A 26-year-old female with ACTH deficiency, hyperprolactinemia and benign intracranial hypertension is reported. Her symptoms of adrenocortical insufficiency and persistent amenorrhea appeared after her last child birth one year previously. During an infectious disease she became critically ill with hypotension and was treated with iv penicillin. A bacterial infection was, however, not diagnosed. After 4 days she developed symptoms and signs of intracranial hypertension. She improved gradually within 10 days without specific therapy against the intracranial pressure. Endocrine investigation disclosed a secondary adrenocortical failure. The lesion appeared to be located in the pituitary gland since plasma ACTH and cortisol did not respond to CRH. A moderately elevated serum PRL was found, whereas the pituitary reserves of TSH, GH, LH and FSH were normal, as was a computed tomographic scan of the pituitary gland. The patient was given cortisone substitution therapy and recovered immediately. Within the following year she regained normal menstruations and became pregnant. A possible autoimmune etiology of her isolated ACTH deficiency precipitated in the puerperium is discussed.
Pancreatic hormone secretion in chronic pancreatitis without residual beta-cell function
Authors: Larsen S. , Hilsted J. , Tronier B. , Worning H.
Published: December 2008

Abstract. Hormonal responses (glucagon, pancreatic polypeptide and somatostatin) to iv glucagon, iv arginine, and ingestion of a mixed meal were investigated in 6 patients with insulin-dependent diabetes secondary to chronic pancreatitis without beta-cell function, in 8 Type I (insulin-dependent) diabetics without beta-cell function, and 8 healthy subjects. No significant differences were found between the two diabetic groups regarding glucagon responses to arginine and meal ingestion. In the patients with diabetes secondary to chronic pancreatitis compared with Type I diabetics and normal controls, the pancreatic polypeptide concentrations were significantly lower and somatostatin concentrations were significantly higher after glucagon, arginine and a mixed meal. Thus, pancreatic glucagon secretion was preserved in patients with insulin-dependent diabetes secondary to chronic pancreatitis, having no residual beta-cell function. These findings suggest that pancreatic glucagon deficiency is not absolute in insulin-dependent diabetes secondary to chronic pancreatitis. A high level of somatostatin may contribute to a lower blood glucose level in patients with chronic pancreatitis.
Improved beta-cell function after intensive insulin treatment in severe non-insulin-dependent diabetes
Authors: Glaser Benjamin , Leibovich Gil , Nesher Rafael , Hartling Svend , Binder Christian , Cerasi Erol
Published: December 2008

Abstract. In Type II, non-insulin-dependent diabetes, insulin secretion is often reduced to the point where oral hypoglycaemic agents fail to control the plasma glucose level. We studied 12 patients (age 41–66 years; 4 lean, 8 obese) with Type II diabetes mellitus for 1–25 years who were uncontrolled despite maximal dose glibenclamide and metformin. After withdrawal of medication, blood glucose control was determined by measuring glucose before and 2 h after each meal for 48 h, and beta-cell function by insulin or C-peptide response to glucagon and to iv glucose. Following these tests, intensive insulin treatment (CSII) was initiated, and near-euglycaemia (mean of 7 daily glucose determinations < 7.7 mmol/l) was maintained for 16.6 ± 1.5 days, at which time the tests were repeated. Mean daily insulin requirement was 61 ± 9 IU (0.81 ± 0.09 IU/kg). Glucose control was improved after cessation of CSII (mean glucose 12.7 ± 0.6 mmol/l after vs 20 ± 1.5 mmol/l before, P <0.005). Maximum incremental C-peptide response improved both to glucagon (214 ± 32 after vs 134 ± 48 pmol/l before, P = 0.05) and to glucose iv bolus injection (284 ± 53 vs 113 ± 32 pmol/l, P < 0.05). Peak insulin response, measured after iv glucose infusion, also tended to be higher in the post-CSII test (42 ± 18 vs 22 ± 5.6 mU/l). Basal and stimulated proinsulin concentrations were high relative to C-peptide levels during the pre-treatment period, but returned to normal after CSII. Thus: 1) adequate blood glucose control could be obtained in most of our patients using moderate doses of insulin even in those who were obese; 2) short-term euglycaemia resulted in improved insulin response to both glucagon and glucose, and reduction of the relative proinsulin secretion; 3) although beta-cell function improved in most patients, only 6 could be adequately controlled with oral agents after hospital discharge. In those patients who do not respond well to conventional treatment, CSII is an attractive alternative.
A specific radioimmunoassay for insulin-like growth factor II: the interference of IGF binding proteins can be blocked by excess IGF-I
Authors: Blum Werner F. , Ranke Michael B. , Bierich Jürgen R.
Published: December 2008

Abstract. A specific antiserum for human IGF-II has been produced by immunizing rabbits against the synthetic peptide IGF-II(33–40). With this antiserum and IGF-II as tracer a radioimmunoassay for IGF-II has been developed. Cross-reactivity with IGF-I was 0.05% and half-maximal displacement occurred at 2.5 μg IGF-II per 1. It was demonstrated that residual IGF-binding protein (IGF-BP) in acid-ethanol extracts interferes with IGF-II measurements and may produce erroneously high values. This interference could be completely blocked by excess IGF-I (25 ng per tube). Utilizing this method IGF-II was measured in subjects at various developmental stages. In newborns, the mean serum level was 237 μg/l (N = 56) with a range of 132–430 μg/l (5- and 95-percentile, respectively). During the first year of life a considerable increase occurred. Thereafter IGF-II increased only slightly with age from 520 μg/l (range 368–735) to 647 μg/l (range 507–823) in adults. In patients with growth hormone deficiency (N = 57) IGF-II levels were significantly (P <0.001) lower than in controls (mean 261 μg/l, range 126–542). It is concluded 1) that residual IGF-binding proteins in acid-ethanol extracts may cause considerable error in IGF-II measurements, and 2) that this interference can be completely blocked by excess IGF-I, if highly specific antisera are used.
Characterization of the effects of clomiphene citrate on reproductive physiology in male rats of various ages
Authors: Brown Janine L. , Chakraborty Prabir K.
Published: December 2008

Abstract. Clomiphene citrate (clomiphene) inhibits reproduction in male rats; however, stimulatory effects have been reported at low doses. Male rats were implanted at 60 (adult), 35 (peripubertal) or 10 (prepubertal) days of age with pellets that delivered 0,0.05, 0.5 or 5.0 mg clomiphene · kg−1 · day−1 and were sacrificed after 7 or 14 days of treatment. Testis weight was unaffected by clomiphene in adult and peripubertal rats, but was reduced by all doses in prepubertal rats. Seminal vesicle and prostate gland weights were decreased to varying degrees by clomiphene in all animals, except seminal vesicle weight in peripubertal rats. Serum LH and testosterone were decreased by most doses in all age groups, whereas pituitary LH was decreased in prepubertal rats only. Pituitary GnRH and testicular LH receptor concentrations were reduced in all treated animals. Serum and pituitary FSH were decreased in pre- and peripubertal rats, whereas testicular FSH receptor concentrations were unaffected by treatment. In summary, 1) reproductive function was compromised by clomiphene and many responses were age-dependent, 2) reductions in gonadotropins suggest that clomiphene decreased their synthesis and/or release, and 3) decreased serum LH and testicular LH receptor concentrations were coupled to reduced testosterone secretion.
Thyroid hormone turnover in patients with small cell carcinoma of the lung
Authors: Faber Jens , Poulsen Sven , Iversen Per , Kirkegaard Carsten
Published: December 2008

Abstract. Patients with small cell carcinoma of the lung often present with symptoms suggestive of hyperthyroidism i.e. weight loss without anorexia. Consequently [125I]T4 and [131I]T3 turnover was studied using simultaneously iv bolus injection and noncompartmental analysis in 6 patients with untreated small cell carcinoma of the lung and 14 normal subjects of comparable ages. Both T4 and T3 production rates were enhanced, T4 production being in median 135 nmol · day−1 · 70 kg−1 (range 111–200) in patients with small cell carcinoma of the lung vs 98 nmol·day−1 ·70 kg−1 (range 69–134) in controls (P < 0.01), and T3 production being 46 nmol · day−1·70 kg−1 (range 33–65) vs 31 nmol ·day−1 ·70 kg−1 (range 24–45) (P < 0.01). The mean transit time was shortened for both T4 and T3, T4 mean transit time being 5.9 days (3.9–8.0 days) vs 8.3 days (6.1–11.2 days) in controls (P < 0.01), and T3 mean transit time being 0.74 days (0.36–0.98 days) vs 1.03 days (0.81–1.45 days) in controls (P < 0.01). Serum total and free T4 and T3 levels were unchanged. Basal serum TSH levels and the TSH response to iv TRH were also normal. Thyroid-stimulating immunoglobulins were only present in the serum in 1 of 6 patients. Thus, thyroid hormone production seemed under pituitary regulation. The peripheral effect of thyroid hormones was evaluated measuring serum sex hormone binding globulin levels, which were increased to in median 270% (77–310%) (P < 0.01) of that in controls, suggesting some degree of hyperthyroidism in liver tissue. One patient was re-investigated after complete remission, which resulted in normalization of T4 and T3 production and mean transit time, as well as serum sex hormone binding globulin levels. The data demonstrate that patients with untreated small cell carcinoma of the lung have enhanced turnover of thyroid hormones, a pattern quite different from that usually seen in non-thyroidal somatic illness.
Sequential presentation of a case of hyperthyroidism with autonomously functioning nodules and Graves' disease in the presence of IgG thyroid stimulators
Authors: Smyth P. P. A. , Neylan D. , McMullan N. M. , Smith D. F. , McKenna T.J.
Published: December 2008

Abstract. The rare occurrence of hyperthyroidism with an autonomously functioning nodule which following 131I therapy presented as toxic diffuse goitre (Graves' disease) is described in a 60 year old male. This progression was characterised by the presence of varying concentrations of IgG thyroid stimulators, thyroid stimulating immunoglobulins and thyroid growth stimulating immunoglobulins, as measured by cytochemical bioassay. It is postulated that the presence of the nodule and its associated hypersecretion of thyroid hormones may have protected the gland from the effects of IgG stimulators by bringing about inhibitory short-loop feedback on normal thyroid cells. It is further suggested that following therapeutic ablation of the nodule, normal thyroid cells became sensitive to the thyroid stimulators with the evolution of typical features of toxic diffuse goitre.
Parallel determination of mineralocorticoid and glucocorticoid receptors in T- and B-lymphocytes of human spleen
Authors: Armanini D. , Endres S. , Kuhnle U. , Weber P. C.
Published: December 2008

Abstract. The binding characteristics of glucocorticoid and mineralocorticoid receptors were determined in T-and B-lymphocytes from the spleen of four deceased kidney donors. The number of glucocorticoid and mineralocorticoid receptors was equivalent in T- and B-cells (respectively, 1308 ± 364 and 1335 ± 520 glucocorticoid receptors per cell, and 174 ± 29 and 164 ± 24 mineralocorticoid receptors per cell). The number of binding sites per cell was 5- to 10-fold higher for dexamethasone than for aldosterone. The apparent dissociation constant of dexamethasone for glucocorticoid receptors was 2-fold higher than that of aldosterone for mineralocorticoid receptors. In conclusion, subpopulations of human lymphocytes have an equal number of glucocorticoid and mineralocorticoid receptors.
Regional differences in the catecholamine content of the rat brain: effects of neonatal castration and androgenization
Authors: Siddiqui A. , Gilmore D. P.
Published: December 2008

Abstract. The long-term organizational influence of perinatal androgen manipulations upon the central noradrenergic and dopaminergic systems was investigated in the rat. Males were castrated or sham-operated upon within 24 h of birth. Newborn females received either five daily sc injections of 100 μg of testosterone in oil, or vehicle only. Groups of animals were then decapitated at ages ranging from 12 to 180 days. Levels of noradrenaline and dopamine were measured in six brain regions using high-performance liquid chromatography with electrochemical detection. The results confirm that the noradrenaline and dopamine content of the brain are affected by perinatal androgen exposure and show that brain catecholamine levels alter during the first six months of life, in some areas merely increasing, but in others rising and later falling. Sex differences in catecholamine levels may be apparent at particular ages, but the direction of the difference is frequently reversed as the animals grow older. In the hypothalamus and amygdala broadly similar patterns of time-related changes in catecholamine levels were observed. However, although in other regions (cerebral cortex, cerebellum, corpus striatum and corpora quadrigemina) sex differences in the noradrenaline and dopamine content were frequently detected, on most occasions they were not affected in any recognizable fashion by steroid manipulation in the newborn. Once adult patterns of gonadotropin secretion and behaviour became established in early adulthood, a functional relationship between brain catecholamine levels and the early effects of testosterone is no longer so apparent. Nevertheless, it would seem that testosterone, acting during the neonatal period, tends to accelerate the fall in brain amine levels that occurs as the animals grow older.
Differential binding of 125I-IGF-I preparations to human fibroblast monolayers
Authors: Conover C. A. , Misra P. , Hintz R. L. , Rosenfeld R. G.
Published: December 2008

Abstract. Specific, high affinity binding of 125I-IGF-I to the type I IGF receptor on human fibroblast monolayers was not altered by varying feeding schedules, serum lots, washing procedures, or incubation times and temperatures. However, markedly different competitive binding curves were obtained when different iodinated IGF-I preparations were used. Five of six radioligands bound preferentially to the type I IGF receptor on human fibroblast monolayers, with 50% displacement at 4–8 μg/l unlabelled IGF-I; with one radioligand a paradoxical 20–200% increase in 125I-IGF-I binding was observed at low concentrations of unlabelled IGF-I, while concentrations as high as 100 μg/l IGF-I failed to displace this radioligand. The latter binding pattern cannot be accounted for by 125I-IGF-I binding to the type II IGF receptor. These data indicate that various radioligands may have preferential affinities for different IGF-I binding sites on human fibroblast monolayers.
7B2, a new protein secreted by human functionless pituitary tumours, in vitro
Authors: Venetikou Maria S. , Ghatei Mohammed A. , Burrin Jacky M. , Latif Sania , Bloom Stephen R.
Published: December 2008

Abstract. A novel pituitary protein, 7B2, of approximately 180 amino acids has been suggested to colocalise with LH in the pituitary gonadotropes. Increased secretion of LH is known to occur in functionless pituitary tumours. We have therefore measured 7B2 immunoreactive equivalents in the 24-h medium of explant pituitary cultures prepared from 17 functionless, 20 somatotropic, 16 PRL secreting and 8 corticotropic adenomas. A synthetic fragment corresponding to amino acids 23–39 of 7B2 was used to raise antisera (rabbits), prepare radiolabel (chloramine T iodination) and also serve as the assay standard. 7B2-immunoreactive equivalents in the medium from the functionless tumours was 517 ± 149 pmol/l, significantly higher than that of the somatotropic tumours (248 ± 90 pmol/l, P < 0.05), prolactinomas (108 ± 37 pmol/l, P < 0.001) and corticotropin producing adenomas (107 ± 77 pmol/l, P < 0.001) (one-way analysis of variance). Gel permeation chromatography of medium obtained from functionless tumours revealed two immunoreactive 7B2 peaks one eluting at a coefficient of 0.28 corresponding to that of normal human pituitary extract and another eluting at a coefficient of 0.59. Gel chromatography profiles of medium obtained from somatotropic tumours contained similar immunoreactive 7B2 peaks (elution coefficient 0.28 and 0.57). These findings demonstrate that 7B2-like material is secreted by pituitary adenomas in explant culture with the highest level from functionless tumour cultures.
Comparative plasma thyroglobulin measurements with three non-cross-reactive monoclonal antibodies in metastatic thyroid cancer patients
Authors: Hüfner M. , Pfahl H. , Bethäuser H. , Heilig B. , Georgi P.
Published: December 2008

Abstract. In 12 normal individuals and 25 patients with metastases of differentiated thyroid cancer, plasma thyroglobulin (Tg) concentrations were measured simultaneously with three immunoradiometric assays. Each of the three systems used a different, non-cross-reactive monoclonal Tg antibody as second antibody. In general, there was a very close correlation between the results of the three different systems in the cross-sectional study of the 25 cancer patients as well as in longitudinal follow-up studies in selected patients. The monoclonal antibody Tg40 produced values about 30% higher than the two other systems. The difference was, however, not statistically significant owing to the large scatter. The monoclonal antibody Tg 13 appeared to be very sensitive to interference with thyroglobulin auto-antibodies. In conclusion, the monoclonal antibodies against the three epitopes tested produced very similar Tg values in normal individuals and 25 patients with metastatic thyroid cancer; however, before more is known about epitope specificity of Tg autoantibodies and heterogeneity of tumour Tg, monoclonal antibodies should be used for routine measurements only with caution.