bluuebunny/crossref_metadata_2025 huggingface dataset:
A controlled clinical trial for the effect of bromocriptine on the adrenal contribution in polycystic ovarian disease
Authors: El Tabbakh Gamal H. , Loutfi Ibrahim A. , Azab Ibrahim , Rahman Hany A. , Aleem Fatma A. , Southern A. Louis
Published: December 2008

Abstract. Adrenal involvement in polycystic ovarian disease was assessed by measuring dehydroepiandrosterone sulphate in 20 polycystic ovarian disease patients. The response of dehydroepiandrosterone sulphate to bromocriptine treatment was compared to that of placebo, both being given for one cycle on a doubleblind, cross over basis. The mean basal DHEA-S was above the upper limit of the normal range (6793 nmol/l) in three patients. The mean basal dehydroepiandrosterone sulphate in the polycystic ovarian disease group was significantly higher than the mean of the normal control group (P < 0.01). Dehydroepiandrosterone sulphate showed a significant drop with bromocriptine as compared to placebo (P < 0.001) and a significant correlation with prolactin both before (P < 0.001) and after treatment with bromocriptine (P < 0.001). These findings support the hypothesis of adrenal involvement in polycystic ovarian disease and prove the significant effect of bromocriptine on the adrenal which might be of therapeutic value.
Cimetidine-induced prolactin release in rats The effect of sex and gonadal steroids
Authors: Watanobe Hajime , Takebe Kazuo
Published: December 2008

Abstract. The cimetidine-induced plasma Prl response was examined in rats of both sexes. First, 10 week old intact adult males and females (dioestrous) were compared. There was no significant difference in the Prl response to cimetidine between the two groups, despite the fact that in adult females the anterior pituitary Prl content was 4 times greater than in males. Second, the effect of gonadal state in adult age on the Prl response to cimetidine was examined in both sexes. In male rats, gonadectomy at the age of 6 weeks significantly reduced the plasma Prl response as well as the pituitary Prl content, both of which were sufficiently restored by testosterone replacement. However, in females, neither gonadectomy at the age of 6 weeks nor subsequent oestradiol replacement affected the Prl response to cimetidine, despite the fact that gonadectomy significantly reduced and oestradiol treatment significantly enhanced the pituitary Prl content. Third, possible permanent effects of the postnatal gonadal milieu on the cimetidine-induced Prl response and the pituitary Prl content were examined in both sexes by castration at varying postnatal ages. The ratio of plasma Prl response to pituitary Prl content was similar in all castrated males. In females, however, the ratio decreased with increasing castration age.

In conclusion, the mechanism of cimetidine-induced Prl release is less sex-dependent than are the mechanisms of Prl release by other Prl secretagogues. First, this may be due to a minor role of oestrogen in females in determining the Prl response to cimetidine. Second, the postnatal ovarian secretions may exert a permanent inhibition of the development of the cimetidine-mobilized anterior pituitary Prl pool.
T-lymphocyte subsets in pregnant women with Graves' disease
Authors: Bizzarro A. , Fontana A. , De Bellis A. , Daponte A. , Iacono G. , Peluso G.
Published: December 2008

Abstract. T-lymphocyte subpopulations, anti-thyroid microsomal antibody titres, and free triiodothyronine and free thyroxine levels were investigated in 10 patients with Graves' disease before, during and after pregnancy. Twenty pregnant subjects and 100 normal age-matched, non-pregnant female volunteers served as controls.

Pregnant patients with Graves' disease showed decrease levels of free triiodothyronine and free thyroxine, and decreased titres of anti-thyroid microsomal antibodies, with clinical remission during the second and third trimesters of pregnancy. Post partum, 9 patients showed clinical relapse, and all showed a return of enhanced levels of free triiodothyronine, free thyroxine and anti-thyroid microsomal antibodies.

The percentage and absolute number of total T-lymphocytes (OKT3+) and OKT4+ cells significantly decreased during pregnancy in patients with Graves' disease and in normal women. Post partum, OKT3+ and OKT4+ cells returned to pre-pregnancy levels in both groups. In Graves patients and in controls, the percentage and absolute number of OKT8+ cells during pregnancy and post partum were not significantly different from pre-pregnancy levels. Lastly, the OKT4+/OKT8+ ratio, which decreased in normal subjects at the three sampling times during pregnancy, decreased only in the last two trimesters of pregnancy in patients with Graves' disease.
Glucose intolerance in thyrotoxicosis roles of insulin, glucagon and somatostatin
Authors: Lam Karen S. L. , Yeung Rose T. T. , Ho Patricia W. M. , Lam S. K.
Published: December 2008

Abstract. The responses in plasma glucose, insulin, C-peptide, glucagon and somatostatin to an oral glucose load were studied in 10 thyrotoxic patients and 10 matched euthyroid controls. The thyrotoxic patients had higher mean fasting plasma glucose (P < 0.05) and responded to oral glucose with an earlier peak at 30 min which was higher than the corresponding glucose level in the controls (P < 0.05). Impaired glucose tolerance was found in 3 patients. Fasting insulin and C-peptide levels were normal in the thyrotoxic patients when corrected for the higher glucose levels. Following glucose ingestion, there was no significant difference between the areas under the insulin or C-peptide curves in patients and controls, but Seltzer's insulinogenic index was reduced in the patients (P < 0.01) suggesting an impaired pancreatic B-cell response to oral glucose. Mean basal glucagon was normal in the thyrotoxic patients. However, while in the controls plasma glucagon became suppressed following glucose ingestion (P < 0.0001), no significant suppression was found in the patients. In the thyrotoxic patients, mean basal somatostatin was normal, but the area under the somatostatin curve following glucose ingestion was significantly increased (P < 0.02). Our findings suggest that décreased glucagon suppression and impaired insulin response after glucose ingestion are involved in glucose intolerance in thyrotoxicosis. Enhanced somatostatin responses to oral glucose in thyrotoxicosis may have contributed to the observed impairment in pancreatic B-cell responsiveness.
Effects of extreme hyperinsulinaemia on serum levels of trace metals, trace metal binding proteins, and electrolytes in normal females
Authors: Nestler John E. , Clore John N. , Failla Mark L. , Blackard William G.
Published: December 2008

Abstract. In order to assess the possible effects of insulin on serum concentrations of trace metals (iron, copper, zinc) and trace metal binding proteins (ferritin, transferrin, coeruloplasmin), five normal females were studied with the hyperinsulinaemic-euglycaemic clamp technique. A 0.1 U/kg insulin bolus was administered, followed by an insulin infusion at a rate of 10 mU/kg/min for 12–16 h. Insulin levels of 1500–2000 μU/ml (9.21– 12.28 nmol/l) were attained. When iron levels in serum were assayed colorimetrically, there appeared to be a progressive rise in the mean concentration during the course of the insulin infusion. Direct analysis of serum samples by atomic absorption spectrophotometry also showed that the level of non-haeme iron increased 3-fold in the serum of the subject with the lowest concentration of this metal at the start of the study. In contrast with the results for serum iron, the levels of ferritin, total iron binding capacity (transferrin), zinc, copper and coeruloplasmin were not altered in any subject during the insulin infusion or at 24 h following discontinuation of the infusion. Within 4 h of institution of the hyperinsulinaemic clamp significant reductions in serum levels of potassium, phosphorus, cholesterol, total protein and albumin were noted. As the insulin infusion progressed, the urea nitrogen, uric acid and bicarbonate levels fell as well. These observations suggest that supraphysiologic hyperinsulinaemia of 12–16 h duration may alter serum levels of iron, but not serum levels of zinc, copper or trace metal binding proteins in some individuals. The mechanism(s) responsible for the rise in mean serum iron, the reductions in serum total protein and albumin, and for the development of a non-anion gap acidosis remain unclear.
Medroxy-progesterone acetate administration to ovariohysterectomized, oestradiol-primed beagle bitches Effect on secretion of growth hormone, prolactin and cortisol
Authors: Rutteman G. R. , Stolp R. , Rijnberk A. , Loeffler S. , Bakker J. A. , Bevers M. M. , Meulenberg P. M. M. , Eigenmann J. E.
Published: December 2008

Abstract. Growth hormone (GH), prolactin (Prl) and cortisol secretion was studied in 5 ovariohysterectomized dogs before and after oestradiol implantation and medroxy-progesterone acetate (MPA) administration. MPA was given at regular intervals during a period of 10 months in a total of 12 injections.

Short-term effects of oestradiol were restricted to significantly enhanced Prl responses to thyrotropin-releasing hormone (TRH). MPA treatment after oestradiol implantation resulted in significanly elevated basal GH levels in all dogs, with a continuing increase in one dog. Only in the latter dog was a significant decrease in basal Prl levels seen. MPA administration did not significantly change Prl responses to TRH. The GH responses to clonidine were significantly reduced at 9 and 16 weeks of oestradiol and MPA treatment. In the one dog which exhibited the greatest rise in basal GH levels, GH responses were completely abolished at 9, 16 and 43 weeks of oestradiol and MPA treatment. TRH never evoked significant GH responses. Both basal and lysine-vasopressin (LVP)-stimulated cortisol levels were significantly suppressed during combined oestradiol-MPA treatment.

These findings denote that in the dog. 1) Oestradiol rapidly induces an enhanced Prl response to TRH. 2) The oestradiol-MPA induced GH overproduction is associated with a reduced responsiveness of GH to clonidine and is not accompanied by GH responsiveness to TRH. 3) Oestradiol-MPA treatment suppresses both basal and LVP-stimulated cortisol secretion.
3,4-Dihydroxypyridine: A potential antithyroid drug
Authors: Hallengren Bengt , Hegarty Mervyn P. , Forsgren Arne , Ericson Lars E. , Melander Arne
Published: December 2008

Abstract. 3,4-Dihydroxypyridine (3,4-DHP), a goitrogenic derivative of the plant amino acid mimosine, has no SH-group, in contrast to conventional antithyroid agents such as methimazole (MMI) and propylthiouracil (PTU). The current in vitro study shows that 3,4-DHP, like MMI and PTU, inhibits iodination of human thyroglobulin and interferes with mitogenic activation of human lymphocytes. This, together with a very low murine bone marrow toxicity, probably related to the absence of an SH-group, makes 3,4-DHP a potential antithyroid drug.
Naloxone enhances the increase in plasma growth hormone induced by α2-adrenergic stimulation in healthy males
Authors: Bramnert Margareta , Hökfelt Bernt
Published: December 2008

Abstract. There is evidence that the α2-adrenergic agonist clonidine interacts with the opioid system. In the present investigations, the effect of naloxone on the increase in plasma GH induced by clonidine and the more specific α2-agonist guanfacine was studied in man. In a single-blind study, five healthy males received in randomized order either the preservatives in the naloxone preparation (control) or naloxone at two different doses (10 or 100 μg/kg) followed by an infusion of either diluted preservatives or naloxone (5 or 50 μg · kg−1 · h−1, respectively). Fifteen min after the bolus dose, clonidine (3 μg/kg) or guanfacine (15 μg/kg) was infused over 10 min in a single-blind order. Both clonidine and guanfacine induced an increase in plasma GH (P < 0.05), Pre-treatment with naloxone at the higher dosage resulted in an enhanced (P < 0.05) GH response to clonidine and guanfacine, respectively, whereas the lower dosage of naloxone was without effect. The increase in plasma GH did not correlate with basal mean arterial blood pressure, nor with the changes in mean arterial blood pressure induced by clonidine or guanfacine.

These results indicate that the increase in plasma GH induced by α2-adrenergic stimulation in normotensive subjects involves opioid receptors with moderate sensitivity to naloxone.
Thyroid autoantibodies: A good marker for the study of symptomless autoimmune thyroiditis
Authors: Betterle C. , Callegari G. , Presotto F. , Zanette F. , Pedini B. , Rampazzo T. , Slack R. S. , Girelli M. E. , Busnardo B.
Published: December 2008

Abstract. In 3737 subjects without clinically thyroid disorders we evaluated the incidence of thyroid microsomal and thyroglobulin antibodies. These autoantibodies were found in 7% of a normal population, in 9% of patients with various non-autoimmune diseases, and in 11–16% of groups who either had or were at risk for autoimmune diseases: patients with IDDM, vitiligo, alopecia areata, idiopathic hypoparathyroidism, Addison's disease, and first-degree relatives of IDDM patients. Functional thyroid evaluation with TRH test was performed in 197 seropositive subjects and 144 seronegative controls. One-quarter (26%) of the subjects with thyroid autoantibodies showed functional abnormalities on TRH testing, whereas only 2.8% of the 144 seronegative controls showed subclinical hypothyroidism. After an observation period of 12–44 months, 102 persistently seropositive subjects were reassessed and 31% of them showed an impairment in TRH test response.
A case of watery diarrhoea syndrome due to an adrenal phaeochromocytoma secreting vasoactive intestinal polypeptide with coincidental autoimmune thyroid disease
Authors: Fisher B. M. , MacPhee G. J. A. , Davies D. L. , McPherson S. G. , Brown I. L. , Goldberg A.
Published: December 2008

Abstract. A 40 year old woman presented with a 10 year history of watery diarrhoea and an acute quadriparesis. On clinical examination there was severe muscle weakness and a nodule was palpable in the thyroid gland. Biochemical testing revealed a hypokalaemia at 1.6 mmol/l. Plasma levels of VIP were raised at 202 pmol/l. CT scanning demonstrated a mass in the area of the left adrenal gland, and isotope scanning of the thyroid gland showed a 'cold' nodule. The plasma catecholamines and calcitonin were elevated. The patient also presented with psychiatric symptoms, and the relevance of these to her condition has been discussed. At operation a left adrenal tumour was removed. Post-operatively the patient's symptoms disappeared and the plasma hormone levels returned to normal values. Histological examination of the tumour revealed a well differentiated phaeochromocytoma which contained VIP and calcitonin. The thyroid nodule was excised and showed histological features of autoimmune thyroid disease. It is suggested that in all cases of the WDHA syndrome where the tumour is in an extra-pancreatic site patients should be screened for phaeochromocytoma.
Investigation into the role of dopamine and lysosomes in the impairment of prolactin transformation and release imposed by long periods of non-suckling in the rat
Authors: Mena F. , Martinez-Escalera G. , Clapp C. , Aguayo D. , Morales M. T. , Grosvenor C. E.
Published: December 2008

Abstract. The transformation of prolactin (PRL) within lactating rat hemipituitary glands incubated for 240 min and the release of the hormone into the incubation medium were progressively reduced by dopamine added to the medium over a 2.3–49 μmol/l range of concentration; the antilysosomal drug chloroquine did not alter these effects of dopamine. In related experiments, the short-term action of dopamine was manifested also upon in vitro transformation, repletion and release of in vivo labelled [3H]PRL, thus indicating that dopamine inhibits all phases of PRL secretion by the lactating rat anterior pituitary (AP). In other experiments, increasing the non-suckling period from 8 to 16 h reduced the pre-suckled concentration of PRL in the lactating rat AP, reduced the ability of the AP to transform PRL in response to suckling, and reduced the capability of the AP of such rats to secrete PRL in vitro. Injecting chloroquine (0.2 mmol/kg ip), haloperidol (0.27 μmol/kg ip) or providing 15–30 min of suckling midway during the 16-h non-suckling period restored each of these functions. Thus, frequent uncoupling of dopamine from its receptor appears necessary to prevent impairment of the suckling-induced transformation mechanism in the lactating rat AP and, presumably, to prevent PRL in the lactotrope from reaching an age where it becomes susceptible to lysosomal degradation.
Osmoregulation of arginine-8-vasopressin secretion in primary hypothyroidism and in Addison's disease
Authors: Laczi F. , Janáky T. , Iványi T. , Julesz J. , László F. A.
Published: December 2008

Abstract. The osmoregulation of arginine-8-vasopressin (AVP) was investigated in 14 patients with primary hypothyroidism and in 6 with Addison's disease. Plasma AVP was measured by radioimmunoassay. Patients with primary hypothyroidism were classified into subgroups with elevated (6.81 ± 1.12 pmol/l) or normal (3.92 ± 0.96 pmol/l) basal levels of plasma AVP. Following the infusion of 2.5% saline, a positive correlation was established between plasma AVP and plasma osmolality. A decreased osmotic threshold was found in hypothyroid patients with augmented basal AVP levels (pAVP = 0.37 (pOs-265), r = 0.71, P < 0.01) as compared with that in hypothyroid patients with a normal AVP level (pAVP = 0.42 (pOs-280), r = 0.93, P < 0.001). A relationship was demonstrated between the alteration in the AVP osmoregulation and the severity of the thyroid insufficiency. Patients with Addison's disease exhibited an increased basal level of plasma AVP (9.59 ± 1.25 pmol/l) and a decreased osmotic threshold (pAVP = 0.42 (pOs-261), r = 0.63, P < 0.01) contrasted to that of healthy volunteers (pAVP = 0.41 (pOs-280), r = 0.83, P < 0.001).

The osmoregulation disturbance of the AVP secretion may play a major role in the impaired water metabolism in primary hypothyroidism and in Addison's disease.
Presence of epidermal growth factor receptors on human thyroid membranes
Authors: Kasai Kikuo , Hiraiwa Masaki , Suzuki Yoshinobu , Emoto Tatsushi , Banba Nobuyuki , Nakamura Tsutomu , Shimoda Shin-Ichi
Published: December 2008

Abstract. The nature of epidermal growth factor (EGF) receptors in normal and pathological thyroid membranes was studied on a crude membrane fraction (10 000 × g pellet) of tissue homogenate. Optimal binding of 125I-EGF to human thyroid membranes was obtained at 25°C with 1-h incubation at pH 7.4. The study revealed the presence of both high and low affinity receptors in normal and pathological thyroid membranes. The association constants of high affinity receptor (3.2 × 10−9 mol/l) and of low affinity receptor (1.8 × 10−8 mol/l) observed in normal thyroid membranes were similar to those of thyroid membranes from neoplastic as well as thyrotoxic thyroid tissues. [3H]thymidine incorporation into DNA of cultured human thyroid cells was stimulated by EGF in a dose-dependent manner. A half-maximal stimulation was found around 1 × 10−10 mol/l. These results suggest that EGF may have a possible role in the regulation of thyroid growth and function in physiological and pathological situations.
A radioimmunoassay for bone Gla protein (BGP) in human plasma
Authors: Johansen Julia S. , Mølholm Hansen J. E. , Christiansen Claus
Published: December 2008

Abstract. To study the value of bone Gla protein (BGP) as a biochemical marker of normal bone physiology and metabolic bone disorders, we have developed a radioimmunoassay (RIA) for the detection of BGP in human plasma. Antibodies were generated in rabbits immunized with purified calf BGP conjugated to thyroglobulin. Human plasma BGP reacted identically with the calf BGP standard, thus demonstrating the suitability of the assay to measure plasma BGP levels in man. The RIA is sensitive, accurate, and technically simple. Plasma BGP levels were determined in normal subjects (N = 35) and in patients with hypothyroidism (N = 10), hyperthyroidism (N = 22) and chronic renal failure (N = 35). The mean (± 1 sem) concentration of plasma BGP in normal subjects was 1.27 ± 0.07 nmol/l. Plasma BGP was significantly increased in patients with hyperthyroidism, 4.04 ± 0.78 nmol/l (P < 0.001) and chronic renal failure, 10.17 ± 2.47 nmol/l (P < 0.001). Low concentrations were found in patients with hypothyroidism, 0.74 ± 0.11 nmol/l (P <0.01). Our studies indicate that plasma BGP provides a useful technique in the diagnosis of patients with bone disease.
Stress-related effects on the secretion of progesterone by the adrenals in castrated male rats presented to stimulus males. Involvement of oestrogen
Authors: Schaeffer C. , Aron Cl.
Published: December 2008

Abstract. Rats were orchidectomized (ORCH) as adults and given 1) successive doses of 0.5 μg or 1.0 μg of oestradiol benzoate (EB) combined or not with dexamethasone (DEXA) at the end of oestrogen treatment; 2) successive doses of olive oil. They were presented to stimulus males on the day of the last EB injection and decapitated immediately after the behavioural test. Animals given EB or olive oil only served as controls. There was a significant rise in blood progesterone concentration in animals given 0.5 and 1.0 μg EB as compared with oil-treated animals. A higher blood progesterone concentration was observed at the end of the behavioural session in oil-treated and 0.5 μ EB-treated ORCH rats than in their isolated counterparts, an effect which appeared not to dependent on lordosis responses to mounting attempts of the males. DEXA completely suppressed the rise in blood progesterone concentration in oestrogenized ORCH rats presented to stimulus males. Presentation of ORCH rats to stimulus males was then concluded to constitute a stressful condition capable of inducing adrenocortical progesterone secretion in ORCH animals.
Evaluation of enzyme inhibitors of pregnancy associated oxytocinase: Application to the measurement of plasma immunoreactive oxytocin during human labour
Authors: Burd J. M. , Davison J. , Weightman D. R. , Baylis P. H.
Published: December 2008

Abstract. The presence of the human placental enzyme, oxytocinase, in blood samples taken during pregnancy causes major methological problems in the radioimmunoassay for plasma oxytocin. Inadequate inhibition of the enzyme activity may lead to spuriously high or low values of plasma oxytocin. This study systematically investigates a variety of enzyme inhibitors. The optimum inhibitory system was obtained by the addition of 10 μl of cold 125 mmol/l 1,10 phenanthrolene and 1 mol/l EDTA per ml of whole blood into the syringe. Complete enzyme inhibition was maintained for up to 60 min, during which time the lithium heparinized plasma samples were extracted by the Florisil method. Following extraction there was no enzyme activity in the extract residue. Concentrations of phenanthrolene and EDTA necessary to eliminate enzyme activity were 50- and 10-fold greater, respectively, than in any previously reported method. Recovery of synthetic oxytocin added to pregnancy plasma with inhibitors was 80% or higher, over the concentration range 1–100 pmol/l. Extract residue could be stored at −20°C for up to 7 weeks. Dilutions of pregnancy plasma extracts ran parallel to the oxytocin standard curve. Studies on plasma concentrations of oxytocin (OT) during the first stage of labour in 6 patients showed that 3 had pulsatile plasma OT, peak values ranging from 4–10 pmol/l in phase with uterine concentrations, but 2 who had regular uterine activity had no episodic changes in plasma OT. One patient with hypocontractile labour had low non-fluctuating plasma OT.
Somatostatin inhibits insulin-stimulated amino acid uptake into cultured rat myoblasts
Authors: Spencer G. S. G. , Hill D. J. , Garssen G. J. , Williams J. P. G.
Published: December 2008

Abstract. The effects of somatostatin on the acute metabolic actions of insulin on newborn rat myoblasts in culture has been examined during monolayer culture. Somatostatin significantly inhibited the insulin-stimulated uptake of [3H]leucine and [3H]amino-isobutyric acid into myoblasts but had no effect on basal (unstimulated) uptake of these two substances. The lowest concentration of somatostatin to have a significant effect was 10 μg/l, and this was apparent in all the experiments undertaken. The inhibitory effect of somatostatin was seen at all effective concentrations of insulin used (0.3–1 U/l). These findings lend support to the concept of an endocrine role for somatostatin in vivo and suggest that a peripheral antagonism may exist between circulating insulin and somatostatin on anabolic processes such as nutrient uptake into cells.
Size heterogeneity of immunoreactive prolactin in patients with prolactinoma
Authors: Allolio B. , Hoeppener A. , Leonhardt U. , Deuβ U. , Winkelmann W.
Published: December 2008

Abstract. We investigated the chromatographic pattern of serum prolactin in 41 patients with prolactinoma and correlated the distribution of immunoreactive prolactin with the clinical variables sex, tumour size, age, and response to bromocriptine therapy. In addition, the effect of long-term storage and repeated freezing and thawing on the different molecular weight forms of prolactin was evaluated. Gel chromatography (column 100 cm × 1.5 cm) was performed in 0.1 mol/l phosphate buffer, pH 7.5, using Ultrogel ACA 54 (LKB).

No correlation of age or the response to drug therapy to the elution pattern of prolactin was found. Females showed a higher percentage of big prolactin than males (10.4 ± 1.2% vs 6.8 ± 0.7%, x̄ ± sem, P <0.05) and patients with microprolactinomas too had a higher percentage of big prolactin than those with macroprolactinomas (11.3 ± 1.8% vs 7.7 ± 0.7%, P <0.05).

Serum samples kept frozen for more than 2 years showed a higher percentage of bigbig prolactin (P < 0.01) than samples stored for less than 12 months suggesting formation in vitro. However, examination of fresh samples prior to freezing also demonstrated bigbig prolactin, indicating that bigbig prolactin circulates in vivo.

Repeated freezing and thawing of bigbig prolactin led to almost complete interconversion to little prolactin without any increase in immunoreactivity. This finding supports the concept that bigbig prolactin represents little prolactin loosely associated to a carrier molecule.
Circulating serum phenylalanine concentrations and the effect of arginine infusion on plasma levels of growth hormone and insulin in treated phenylketonuric children
Authors: Rosskamp R. , Mallmann R. , Liappis N. , Soetadjii S.
Published: December 2008

Abstract. According to desired phenylalanine (Phe) levels of 50–80 mg/l during treatment, three groups of patients with classical phenylketonuria (PKU) (5.3–17.1 years) were formed. They were investigated for their growth hormone (GH) and insulin response to arginine infusion: Group I (N = 5) had Phe levels below (22 ± 4 mg/l), group II (N = 3) within (61 ± 6 mg/l), and group III (N = 3) above therapeutic limits (156 ± 3 mg/l). Nine children (5.2–14.5 years) with short stature served as controls. Whereas group I and II PKU children showed normal GH response to arginine infusion, group III children exhibited impaired GH response expressed as integrated GH response (218 ± 38.6 μg · 1−1 · 2 h vs 911 ± 145 μg · 1−1· 2 h; P <0.01) or peak GH response (6.6 ± 1.2 μg/l vs 18.7 ± 2.3 μg/l; P < 0.05). Integrated insulin responses did not differ between the three PKU groups but were significantly higher in all PKU patients compared with controls (4903 ± 421 mU/l vs 2750 ± 378 mU/l; P < 0.01). However, this reflects impaired insulin secretion in children with constitutional delay of growth and adolescence rather than hyperinsulinism in PKU patients.
Thyroxine in unextracted urine
Authors: Orden I. , Pie J. , Juste M. G. , Marsella J. A. , Blasco C.
Published: December 2008

Abstract. The aim of this work was to estimate the daily urinary excretion of free and conjugated thyroxine using a direct radioimmunoassay and enzyme hydrolysis. The renal clearance of free T4 was also determined. The mean urinary values of free and total T4 (mean ± 1 sd) in 112 euthyroid controls were 1353 ± 496 and 1855 ± 651 pmol/24 h, respectively. Urinary excretion of free hormone in 13 hyperthyroid patients was 5552 ± 4320 pmol/24 h and total T4 was 8122 ± 7219 pmol/24 h. Urinary free T4 excretion was 223 ± 223 pmol/24 h in hypothyroid patients and total T4 was 542 ± 490 pmol/24 h. These results indicate that daily urinary T4 excretion is a good indicator of thyroid function. The mean renal clearance of free T4 was 52 ± 19 ml/min (mean ± 1 sd) in euthyroid patients, 53.7 ± 12.3 ml/min in hyperthyroid patients, and 67.6 ± 13.1 ml/min in hypothyroid patients. We estimated the endogenous creatinine renal clearance as a control of the renal filtration rate. The data suggest that there is T4 filtration of unbound T4 and partial tubular reabsorption. Further experimental studies will be necessary to clarify the renal handling of thyroxine as well as the fate of reabsorbed T4.
Differential responses of plasma oxytocin and vasopressin to dehydration in non-stressed sheep
Authors: Thornton S. N. , Parrott R. F. , Delaney C. E.
Published: December 2008

Abstract. Group housed, castrated rams (N = 10) were studied over a 2 day period. Water was available ad libitum during day 1 (control) but was withheld throughout day 2 (experimental). On both days, blood was collected by jugular venepuncture at 10.30 h, and then again 2, 4, 6 and 24 h later. Plasma samples were analysed by radioimmunoassay for arginine vasopressin (AVP), oxytocin and cortisol content and measurements were also made of the haematocrit and plasma osmolality and electrolyte (Na+, Cl−) concentrations. After 24 h water deprivation there was a significant increase in plasma AVP levels but no changes in oxytocin or cortisol concentrations. Dehydration also significantly depressed the haematocrit and increased plasma osmolality and electrolyte concentrations.
Strong association between HLA DRw9 and Hashimoto's thyroiditis in Southern Chinese
Authors: Hawkins B. R. , Lam K. S. L. , Ma J. T. C. , Wang C. , Yeung R. T. T.
Published: December 2008

Abstract. The distribution of HLA-A, -B, and -DR antigens in 53 Southern Chinese patients with Hashimoto's thyroiditis including 33 with goitre and 20 without goitre was compared with the distribution in 100 Southern Chinese controls. There was a significantly increased prevalence of HLA Bw46 in the non-goiterous patients and of HLA DRw9 in both groups of patients, but only for HLA DRw9 in the goiterous group was the increase significant after adjustment for the number of antigens studied. Based on these findings and those in other autoimmune diseases it is considered that the haplotype Bw46, DRw9 in Chinese takes the place of B8, DR3 in Caucasians in carrying genes which predispose to the development of autoimmune disease.
Foetal steroid binding protein in British and Japanese women
Authors: Iqbal M. Jawed , Forbes Alastair , Wilkinson Mark L. , Moore John W. , Williams Roger , Bulbrook Richard D.
Published: December 2008

Abstract. In order to examine the newly-discovered sex-steroid binding protein, foetal steroid binding protein (FSBP) in different populations, its binding characteristics and its level were studied by two-tier column ligand binding assay and enzyme-linked immunosorbent assay (ELISA) respectively. In 10 Japanese premenopausal women, analysis of 5α-dihydrotestosterone (DHT) binding in the Cibacron Blue 3GA-Sepharose 6B portion of the column showed a rising plateau pattern with a mean maximum binding of 31.1 ± 7.41%, whereas of 9 similar British women, 8 displayed unsaturable, non-cooperative binding of 11.6 ± 8.22% (P < 0.01). After partial purification of FSBP in these samples, the protein exhibited saturable binding kinetics, median binding 25 (interquartiles 23–34) and 19 (13–25) nmol DHT/l in Japanese and British women, respectively (P < 0.05). By analyzing FSBP by ELISA in 56 Japanese (45 premenopausal) and 59 British (25 premenopausal) women, higher levels were obtained in the whole Japanese group (P = 0.0016) and in the premenopausal Japanese women (P = 0.018) than in their British counterparts. In both nationalities, FSBP levels were higher in premenopausal women, and there was a significant negative correlation of FSBP with age in both populations, particularly in postmenopausal women. FSBP levels did not correlate with weight, parity, sex hormone binding globulin or albumin levels. The influence of FSBP on free steroid levels remains unclear, but some relationship with ovarian function seems a possibility.
Characterization of growth hormone-releasing hormone stimulation of the endocrine pancreas: Studies with α- and β-adrenergic and cholinergic antagonists
Authors: Hermansen K. , Kappelgaard A. M.
Published: December 2008

Abstract. The 40 aminoacids residue of pancreatic growth hormone-releasing hormone stimulates the secretion of insulin, glucagon, an somatostatin from the pancreas. To determine whether this stimulation of islet hormone secretion is mediated via adrenergic or cholinergic receptor sites, we studied the effects of 30 nmol/l of the growth hormone-releasing hormone on the release of insulin, glucagon, and somatostatin in the presence of either α-adrenergic (phentolamine), β-adrenergic (propranolol) or cholinergic (atropine) blocking agents. The responses to the growth hormonereleasing hormone were not significantly modified by adrenergic or cholinergic blockers. The findings rule out an interaction with adrenergic and cholinergic receptors on islet cells. It is at present unknown whether the growth hormone-releasing hormone stimulates islet hormone secretion via an interaction with specific growth hormone-releasing hormone receptors or vasoactive intestinal peptide receptors.
Demonstration of specific dopamine receptors on human pituitary adenomas
Authors: Koga Masafumi , Nakao Haruyoshi , Arao Masayo , Sato Bunzo , Noma Keizo , Morimoto Yasuhiko , Kishimoto Susumu , Mori Shintaro , Uozumi Toru
Published: December 2008

Abstract. Dopamine receptors on human pituitary adenoma membranes were characterized using [3H] spiperone as the radioligand. The specific [3H]spiperone binding sites on prolactin (PRL)-secreting adenoma membranes were recognized as a dopamine receptor, based upon the data showing high affinity binding, saturability, specificity, temperature dependence, and reversibility. All of 14 PRL-secreting adenomas had high affinity dopamine receptors, with a dissociation constant (Kd) of 0.85 ±0.11 nmol/l (mean ± sem) and a maximal binding capacity (Bmax) of 428 ± 48.6 fmol/mg protein. Among 14 growth hormone (GH)-secreting adenomas examined, 8 (57%) had dopamine receptors with a Kd of 1.90 ± 0.47 nmol/l and a Bmax of 131 ± 36.9 fmol/mg protein. Furthermore, 15 of 24 (58%) nonsecreting pituitary adenomas also had dopamine receptors with a Kd of 1.86 ± 0.37 nmol/l and a Bmax of 162 ± 26.0 fmol/mg protein. These results indicate that some GH-secreting adenomas as well as some nonsecreting pituitary adenomas contain dopamine receptors. But their affinity and number of binding sites are significantly lower (P < 0.05) and fewer (P < 0.001) respectively, than those in PRL-secreting adenomas.
Evidence for diverse structural variations of the forms of human FSH within and between pituitaries
Authors: Wide Leif
Published: December 2008

Abstract. The biological activity of FSH in vitro (B-vitro) was compared with its radioimmunological (RIA) activity in 38 pituitary extracts from men and women. The B-vitro method was based upon the estimation of oestradiol produced by cultured Sertoli cells from 10-day-old rats. The mean B-vitro/RIA ratios for FSH of men and young and elderly women were almost identical. The mean values of median charge of the forms of FSH differed significantly between the three groups of human adults. The B-vitro/RIA ratio of different forms of FSH, separated by electrophoresis of 14 individual pituitary extracts, was higher for less negatively charged than for more negatively charged forms. Some forms of FSH with the same charge and separated from different pituitary extracts, e.g. from a young and an elderly woman, had significantly different B-vitro/RIA ratios. This ratio, thus, was not related to the charge per se of the hormone. However, the relation between the B-vitro/RIA ratio and the charge of FSH was similar for individual pituitary extracts when charge was expressed in relation to median charge. The results suggest that different molecular structural variations of FSH are involved in the polymorphisms observed within and between individual pituitaries. In human adults, the variation of FSH between the pituitaries mainly affects the metabolic clearance rate (MCR) of the hormone, whereas the variation within the individual pituitary affects both the MCR of the hormone and its biological effect at the target cell.
A sensitive and practical assay for thyroid-stimulating antibodies using FRTL-5 thyroid cells
Authors: Kasagi Kanji , Konishi Junji , Iida Yasuhiro , Tokuda Yasutaka , Arai Keisuke , Endo Keigo , Torizuka Kanji
Published: December 2008

Abstract. A sensitive, precise and practical assay for thyroid stimulating antibodies was developed in which poorly differentiated rat thyroid cells (FRTL-5) were exposed to crude immunoglobulin fractions precipitated from serum with 15% polyethylene glycol under hypotonic conditions. After the incubation at 37°C for 2 h, cAMP released into Hank's medium without NaCl was determined by radioimmunoassay. The removal of NaCl from the isotonic Hank's medium greatly enhanced cAMP production in response to both TSH and thyroid stimulating antibodies. The assay was sensitive enough to elicit an approximately 30-fold increase in cAMP at 10 mU/l bovine TSH. Thyroid stimulating activities measured using FRTL-5 cells significantly correlated with those measured using cultured porcine (r = 0.918, N = 72) or human (r = 0.830, N = 23) thyroid cells. Thyroid stimulating activities were detected in all of the 50 patients with hyperthyroid Graves' disease, the 14 patients with recurrent hyperthyroid Graves' disease, and the 25 patients with ophthalmic Graves' disease. Thyroid stimulating activity was also detected in some patients (9/24, 37.5%) with Hashimoto's thyroiditis whose serum TSH concentrations were higher than 30 mU/l. However, it was completely abolished by pre-treatment of the sera with anti-TSH antibodies. Although thyroid stimulating activities were detected in one of the patients with simple goitre (N = 10) and in one with thyroid cancer (N = 10), none of the patients with silent thyroiditis (N = 7), adenomatous goitre (N = 11), and thyroid adenoma (N = 9) were positive for thyroid stimulating antibodies.
Subcellular location of IGF-I in chondrocytes from rat rib growth plate
Authors: Wroblewski J. , Engström M. , Skottner A. , Madsen K. , Friberg U.
Published: December 2008

Abstract. Ultrathin cryosections of segments of growth plates from rat rib and isolated, gelatin-embedded chondrocytes from the same source were used to demonstrate the ultrastructural location of IGF-I in the different layers of the growth plate. Sections were incubated with a polyclonal rabbit antiserum to free IGF-I and colloidal gold coated with goat anti-rabbit IgGs. The gold label was present in all chondrocytes, localized almost exclusively to the cytoplasm. Particularly the cells in the proliferating zone displayed considerable amounts of gold label. In these cells, gold label was predominantly present over the rough endoplasmic reticulum and membrane bound vesicles, with only negligible gold label over the nuclei and cartilage matrix. The distribution of gold label in the chondrocytes from the proliferating zone, especially in the rough endoplasmic reticulum, strongly suggests that IGF-I can be synthesized by these cells. However, further studies are needed to verify whether there is a local synthesis of IGF-I in the chondrocytes and whether it is under control of growth hormone.
Increased luteinizing hormone sensitivity to dopaminergic inhibition in Graves' disease
Authors: Tourniaire J. , Borson-Chazot F. , Fevre-Montange M. , Chalendar D. , Charrie A. , Claustrat F. , Dechaud H.
Published: December 2008

Abstract. The effect of dopamine infusion (4 μg · kg−1 · min−1 from 9.00 to 13.00 h) on serum LH and FSH concentrations were studied in 15 patients (10 women, 5 men) with diffuse toxic goitre, and 10 healthy subjects (6 women, 4 men). Basal serum LH (17.0 ± 0.8 IU/l) and oestradiol (women: 3.74 ± 1.84; men: 3.05 ± 0.77 pmol/l) were elevated in patients, whereas serum FSH and PRL were normal. Dopamine infusion did not modify serum FSH levels, but significantly depressed LH concentration in both hyperthyroid and healthy subjects. The LH decrement was more pronounced (P < 0.01) in patients with Graves' disease (8.4 ± 1.4 IU/l) as compared with controls (2.3 ± 0.9 IU/l). There was a positive correlation between the maximum net decrease and the basal LH concentration (r = 0.95). The per cent decrease of LH levels in the hyperthyroid patients (54 ± 4) was higher (P < 0.001) than that in the controls. The finding of enhanced sensitivity to dopamine inhibition in thyrotoxic patients suggests that their inappropriately elevated serum LH levels may result in part from a reduced dopaminergic inhibition of LH secretion.
Neuropeptide Y directly inhibits growth hormone secretion by human pituitary somatotropic tumours
Authors: Adams Eric F. , Venetikou Maria S. , Woods Christine A. , Lacoumenta S. , Burrin J. M.
Published: December 2008

Abstract. Neuropeptide Y (NPY) is a 36 amino acid peptide, widely distributed throughout the brain and is found in hypothalamic neurones. This latter finding suggests that NPY may possess a hypophysiotropic function. A number of studies have demonstrated effects of NPY on LH and GH secretion by rat pituitary cells. We report here the results of experiments investigating the effects of NPY on GH secretion by tumorous human somatotropic pituitary cells in culture. NPY (0.25–25 nmol/l) inhibited GH secretion by 20–53%, the maximal effect depending upon the tumour studied. The potency of NPY was less than that of somatostatin (SRIH). The stimulatory effects of growth hormone releasing factor (GHRH) and theophylline were reduced by NPY, but NPY did not modify the inhibitory effect of SRIH on GH secretion. It is concluded that NPY may be involved in the control of GH secretion, at least by tumorous human pituitary somatotropes.
Uterotonic activity and myometrial receptor affinity of 1-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin
Authors: Atke Anders , Vilhardt Hans
Published: December 2008

Abstract. The contractile effect of the analogue 1-deamino-1-carba-2-tyrosine(O-methyl)-oxytocin (carbetocin) on isolated myometrial strips from rats was compared with that of oxytocin. The uterotonic activity of the analogue was 15 ± 3 IU/mg as compared with 438 ± 41 for oxytocin, however, the response was more prolonged and could not be abolished by washing of the preparation. Despite the low biological activity of carbetocin, its binding affinity to receptors of isolated myometrial plasma membranes was of the same order of magnitude as that of oxytocin. On the basis of the present results it is concluded that a longer half-life of the analogue at the receptor compartment may be a contributing factor to the prolonged uterotonic effect observed in vivo.
Demonstration of glucose inhibition of insulin release in the presence of diazoxide
Authors: Bergsten Peter , Hellman Bo
Published: December 2008

Abstract. β-Cell-rich pancreatic islets from ob/ob mice were taken for measurements of insulin release in response to glucose after culture in RPMI 1640 medium. The stimulatory effect of 20 mmol/l glucose was converted into an inhibition when the medium was supplemented with 400 μmol/l diazoxide. Glucose inhibition of insulin release was observed when the islets had been cultured in the presence of 1 or 20 mmol/l glucose in media either containing or lacking Ca2+. The data provide further evidence for an inhibitory component in the action of glucose on insulin release, suggesting that glucose stimulation of the Ca2+ efflux is essential for the appearance of this inhibition.
Physiological aspects of the thyroid trapping function and its suppression in iodine deficiency using 99m Tc pertechnetate
Authors: Bähre Manfred , Hilgers Reinhard , Lindemann Corinna , Emrich Dieter
Published: December 2008

Abstract. In an area of iodine deficiency, we investigated 190 individuals with and without euthyroid endemic goitre, who had a normal TSH response after TRH and an entirely homogeneous thyroid scintigram before and under suppression. In these subjects, the thyroid uptake of 99mTc pertechnetate, as a measure of the iodide trapping function, was determined before (TcUb) and under suppression (TcUs), using quantitatively evaluated scintigraphy. In this control group of individuals, without evidence of autonomy, the reference ranges of TcUb and TcUs were determined. The upper limit of the reference range for TcUb was 7.4% of the tracer activity injected, and for TcUs 1.6%. The reference range of TcUs is to be used to detect accurately thyroid autonomy in vivo. In addition, factors affecting the thyroid trapping function were investigated. With decreased iodine supply, trapping before suppression was increased, compensating for iodine deficiency. The effect of TSH on the trapping function was secondary, indicating that, to a considerable degree, the follicular cells adapt their iodide trapping to the iodine supply. The trapping before and under suppression increased with the estimated thyroid weight. ΔTSH after TRH stimulation measured before suppression correlated inversely with the trapping under suppression. The two latter observations suggest that there is a continuum between low and increased levels of the TSH-independent thyroid function, even among these selected individuals without primary evidence of autonomous tissue. A correlation of the trapping function with sex, oestrogen treatment, and goitre type was not demonstrable. Age was found to have a small influence. Except for iodine contamination, the factors affecting the pertechnetate uptake of the thyroid, can be neglected under routine conditions.
Inhibition of Δ5-3β hydroxysteroid dehydrogenase activity in pre-implantation mouse embryos and their implantation by sheep ovarian follicular fluid peptide
Authors: Joshi N.J. , Moodbidri S. B. , Nandedkar Tarala D.
Published: December 2008

Abstract. The activity of Δ5-3β hydroxysteroid dehydrogenase (Δ5-3β HSD) in pre-implantation mouse embryos was inhibited following their prior incubation with partially purified sheep ovarian follicular fluid peptide (OFFP). OFFP, 5 μl, injected into the uterine lumen of day 4 pregnant mice impaired the ensuing implantation of embryos. Our observations suggest that OFFP may inhibit steroid metabolizing activity in pre-implantation embryos and thereby interfere with the process of implantation.