bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of measurements of serum free T3 concentration by equilibrium dialysis, free T3 index, and T3: TBG ratio in thyroidal and non-thyroidal illnesses
Authors: Konno Norimichi , Nakazato Takashi , Hagiwara Kohji , Taguchi Hideo
Published: December 2008

Abstract. The present study was undertaken and compare the methods for measuring free T3 (FT3) by equilibrium dialysis, free T3 index (FT3I), and T3:T4-binding globulin (T3/TBG) in 40 healthy subjects, 26 patients with hyperthyroidism, 36 patients with hypothyroidism, 16 women in the 3rd trimester of pregnancy, 5 euthyroid subjects with low TBG, and 24 patients with non-thyroidal illnesses (NTI) with normal or low serum T3 concentration. Both FT3I and T3/TBG correlated significantly with FT3 (r = 0.98, P < 0.001 and r = 0.92, P< 0.001, respectively) when the data from all subjects were analyzed together. When each group was analyzed separately, FT3I still correlated significantly with FT3 in all groups (r = 0.67–0.97) except in the NTIs with low T3 (r = 0.18). The correlation of T3/TBG with FT3 was also significant in all groups (r = 0.60–0.88) other than the euthyroid with low TBG (r = 0.32) and NTIs with low T3 (r = 0.04). Both FT3I and T3/TBG values agreed well with the FT3 level in hyper- and hypothyroid subjects. In euthyroidism with abnormal TBG level, FT3I agreed well with FT3. However, T3/TBG gave a falsely lower FT3 when the TBG level was high, and a falsely higher FT3 when the TBG was low. In NTIs with normal T3, both FT3I and T3/TBG agreed well with FT3, but FT3I and T3/TBG values were all subnormal in NTIs with low T3, where FT3 ranged from normal to subnormal. These data suggest that 1) both FT3I and T3/TBG may be equally useful for an assessment of FT3 level in hyperand hypothyroidism, 2) FT3I may be superior to T3/TBG in euthyroidism with abnormal TBG concentration in serum, and 3) neither FT3I nor T3/TBG may be valid for an indirect measure of FT3 in NTIs with low serum concentration of T3.
Heterogeneity of immunoreactive calcitonin in human milk
Authors: Bucht E. , Arver S. , Sjöberg H. E. , Löw H.
Published: December 2008

Abstract. Immunoreactive calcitonin (ICT) has been detected in human milk by radioimmunoassay (RIA), using antibodies raised against synthetic human calcitonin (hCT). The level of ICT was 10–40 times higher than the reference level of human serum. Gel chromatography of human milk disclosed a molecular weight heterogeneity of ICT, with at least two forms larger than the monomer (Mr > 70 000 and 30 000 approximately). The 30 000 peak constituted the major fraction of ICT. No detectable amount of ICT was coeluted with [125I]CT. Reduction with disulphide cleaving agents, denaturation or acidification did not alter the gel chromatographic properties of ICT, while tryptic digestion caused partial degradation of ICT and formation of new ICT molecules with an approximate molecular weight of 6000.
Carpenter's syndrome with empty sella and abnormal LRH and TRH response
Authors: Verdy M. , Dussault R. G. , Verrault R. , Bolté E.
Published: December 2008

Abstract. Two sisters with Carpenter's syndrome and empty sella have been evaluated for pituitary function. The TRH injection brought a normal response of TSH and prolactin. There were no change in FSH and LH, but a paradoxical increase of growth hormone and cortisol. The injection of LRH brought a normal response of FSH and LH, no change in TSH and cortisol values and a paradoxical increase in prolactin and growth hormone.
The influence of pituitary and gonadal hormones on serum levels of pregnancy-associated murine protein-1
Authors: Hau J. , Gidley-Baird A. A. , Teisner B. , Svendsen P. , Westergaard J. G.
Published: December 2008

Abstract. Hypophysectomy of female mice resulted in the disappearance of pregnancy-associated murine protein-1 (PAMP-1) from the circulation within a week. Maintenance of physiological levels of oestrogen, progesterone, testosterone, LH, FSH or prolactin was not sufficient to maintain a normal PAMP-1 level in the hypophysectomized animals. However, administration of oestrogen in large doses to adult male mice with undectable levels of circulating PAMP-1 caused PAMP-1 to appear in the blood. Testosterone treatment of females inhibited the PAMP-1 synthesis.
Relations between thyroid function, hepatic and lipoprotein lipase activities, and plasma lipoprotein concentrations
Authors: Valdemarsson Stig , Hansson Per , Hedner Pavo , Nilsson-Ehle Peter
Published: December 2008

Abstract. Lipoprotein concentrations and activities of lipoprotein lipase (LPL) and hepatic lipase (HL) were measured in 70 subjects with thyroid function ranging from overt hypothyroidism over subclinical hypothyroidism and euthyroidism to hyperthyroidism.

In parallel with serum T3 (S-T3) concentrations increasing from low in hypothyroidism to high in hyperthyroidism there were gradually higher HL activities over the full spectrum of thyroid function, accompanied by decreasing levels of total and low density lipoprotein (LDL) cholesterol. High density lipoprotein (HDL) cholesterol was lower (P < 0.05) in hyperthyroidism than in euthyroidism but not significantly changed in the hypothyroid groups. HL was correlated to S-T3 (r = 0.77, P< 0.001), LDL cholesterol to log S-T3 (r = -0.76, P < 0.001), and LDL cholesterol to log HL (r = -0.55, P <0.001).

The activity of LPL was decreased (P< 0.001) in overt hypothyroidism compared to euthyroidism but, in contrast to HL, the activity of LPL was not increased in hyperthyroidism. The plasma triglyceride (P-TG) concentration was elevated (P< 0.01) in overt hypothyroidism but not significantly changed in subclinical hypothyroidism or in hyperthyroidism. The LPL activity was correlated to log S-T3 (r = 0.45, P < 0.001), P-TG to log S-T3 (r = -0.37, P< 0.01) and P-TG to log LPL activity (r= -0.71, P<0.001).

Our results demonstrate that thyroid hormones influence HL and LPL activities in different ways, suggesting different mechanisms of action. Changes in HL activity seem to be an important mechanism for the disturbance of cholesterol metabolism in thyroid dysfunction while the thyroid hormone influence on LPL seems to be of importance mainly for the disturbance in triglyceride metabolism.
Evidence for α-adrenergic receptors acting through the guanylate cyclase system in human cultured thyroid cells
Authors: Brandi Maria Luisa , Rotella Carlo M. , Tanini Annalisa , Toccafondi Roberto S.
Published: December 2008

Abstract. In order to investigate the presence of α-adrenergic receptors in human thyroid, we have studied the effect of α-adrenergic agonists and antagonists on cGMP cellular content of human thyroid cells in primary culture. Epinephrine as well as TSH were not able to modify the cGMP cellular levels, while norepinephrine significantly increased cGMP accumulation already at 10 nm, a dose inactive on cAMP accumulation. A non selective α-adrenergic antagonist, phentolamine, significantly inhibited cGMP accumulation induced by norepinephrine. Norepinephrine-induced cGMP accumulation was unaffected by prazosin, an α1-adrenergic antagonist, but was abolished by yohimbine, an α2-adrenergic antagonist. Phenylephrine, an α-adrenergic agonist, produced an increase of cellular cGMP levels without modifying cAMP content. In the presence of TSH, the cGMP response to norepinephrine was not modified; however, the increase of cAMP levels was inhibited by norepinephrine at doses inactive on cAMP accumulation, but active on cGMP levels. The present results demonstrate the existence in human thyroid cells of α2-adrenergic receptors, regulating the guanylate cyclase system. It may be postulated that the counter-regulation exerted by α-adrenergic agonists on the response to TSH operates on the TSH-dependent adenylate cyclase.
Oral glucose tolerance test and insulin sensitivity in low insulin responders
Authors: Wajngot A. , Luft R. , Efendić S.
Published: December 2008

Abstract. Oral and iv glucose tolerance, insulin response to iv and oral glucose load as well as insulin sensitivity were evaluated in 58 'low insulin responders'. They were selected from a group of 226 healthy subjects with normal fasting blood glucose and normal iv glucose tolerance test on the basis of a low insulin response during a standardized glucose infusion test (GIT). The insulin response to GIT was analysed by parameter identification in a mathematical model (parameter KI). Insulin sensitivity was also measured by computer analysis of GIT (parameter KG) and, in a limited group of subjects, by a somatostatin infusion test.

Thirty-three low insulin responders had normal OGTT, whereas 5 demonstrated borderline-1, 16 borderline-2, and 4 decreased OGTT. The first group of subjects demonstrated normal or enhanced insulin sensitivity. Borderline and decreased OGTT, in most instances, was accompanied by decreased insulin sensitivity, implying that a subgroup of low insulin responders exhibited signs of both impaired insulin response to glucose and insulin resistance. Since these defects characterize manifest type-2 diabetes, these subjects possibly may run a high risk to develop this type of diabetes. On the other hand, low insulin response in combination with increased insulin sensitivity may reflect adaptation of the secretory capacity of B-cells to the need of insulin.
Effects of angiotensin II and ACTH on normal and tumourous human adrenocortical cells
Authors: Belmega Wolfgang , Oelkers Wolfgang , Belkien Lutz , Shirpai Monika , Fiedler Ulrich , Häring Rudolf
Published: December 2008

Abstract. Isolated adrenocortical cells from 6 patients with a 'normal' zona fasciculata, 4 patients with a 'normal' zona glomerulosa, and tumour cells from 1 adrenocortical adenoma and 1 carcinoma were incubated with and without increasing concentrations of ACTH 1–24 (10−13 m to 10−9 m) or Asp1-Ile5-angiotensin II (10−11 m to 10−7 m). In 4/5 'normal' cases, cortisol was clearly stimulated by 10−13 m ACTH. The maximum of the dose-response curve (5-fold stimulation) was reached at 10−10 m ACTH. Angiotensin II (All) started to stimulate 'normal' cells at 10−11 m with a maximum (2-fold stimulation) at 10−9 m. Aldosterone production by 'normal' cells was less markedly stimulated by ACTH and All, although the threshold doses for both peptides were similar to those of the cortisol response curves.

The cells of the adrenocortical adenoma from a patient with Cushing's syndrome produced large amounts of cortisol and small amounts of aldosterone, both steroids being clearly stimulated by ACTH and AII. The adrenocortical carcinoma cells produced small amounts of cortisol and no aldosterone. Cortisol production responded to ACTH, but not to AII.

The results suggest that an activated renin-angiotensin system may stimulate the zona fasciculata, since 10−11 m All (= 10 pg AII/ml) is a normal plasma All concentration on an unrestricted diet. Clinical evidence supporting this thesis is reviewed. However, cortisol production itself will rarely be increased by All in vivo, since a downregulation of ACTH would occur.
Synaptosomal T3 binding sites in rat brain: their localization on synaptic membrane and regional distribution
Authors: Mashio Yasuo , Inada Mitsuo , Tanaka Kiyoshi , Ishii Hitoshi , Naito Koichi , Nishikawa Mitsushige , Takahashi Kiyoyuki , Imura Hiroo
Published: December 2008

Abstract. Previous studies have shown the existence of specific high affinity T3 binding sites in rat cerebrocortical synaptosomes. In this study, to define the localization of the binding sites, T3 binding to disrupted synaptic membrane fractions was compared with the binding to intact synaptosomes obtained from the rat cerebral cortex. Scatchard analysis revealed two orders of T3 binding sites with almost identical apparent dissociation constant (Kd) in synaptosomes and synaptic membrane fractions. However, the maximal binding capacity (MBC) of the higher affinity binding sites for synaptic membrane fractions was significantly greater than that for intact synaptosomes (4.2 ± 0.2 vs 3.0 ± 0.3 pg T3/mg protein).

Regional distribution of the synaptosomal T3 binding sites in various areas of the rat brain was also studied. The Kd values were not significantly different in discrete brain regions. On the other hand, the MBCs of the higher affinity binding sites were greater in the cerebral cortex and hypothalamus (72.8 ± 1.4 and 64.8 ± 9.5 pg T3/g tissue) than in the cerebellum (22.1 ± 1.6 pg T3/g tissue). Similar difference was also observed in the lower affinity sites.

These results indicate that the specific T3 binding sites in brain synaptosomes are localized mainly on synaptic membranes and that the MBC is different in discrete brain regions.
Lack of effect of desglycinamide-arginine-vasopressin (DGAVP) on memory in patients with Korsakoff's syndrome
Authors: Laczi F. , Van Ree J. M. , Balogh Lujza , Szász Anna , Járdánházy T. , Wágner A. , Gáspár L. , Valkusz Zsuzsa , Dobranovics Ilona , Szilárd J , László F. A. , De Wied D.
Published: December 2008

Abstract. The effect of desglycinamide9-[Arg8]-vasopressin (DGAVP) on memory processes was studied in patients with Korsakoff's syndrome. Intranasal treatment with DGAVP for 7 days affected neither attention nor short- and long-term memories. It is suggested that treatment with DGAVP is not indicated for all types of memory disorders, and that the beneficial effect of this treatment may depend on the integrity of certain brain structures.
Different aetiologies in post-partum thyroiditis?
Authors: Dahlberg Per Anders , Jansson Rolf
Published: December 2008

Abstract. During a 4 year period 19 women with post-partum onset of thyroid dysfunction have been seen in our clinic. Five women had high radioiodine uptake thyrotoxicosis (Graves' disease). Twelve women had hypothyroid symptoms starting within 3–6 months of delivery. All of these women had thyroid microsomal and/or cytoplasmic autoantibodies and thyroid lymphocytic infiltration suggesting aggravation of pre-existing subclinical autoimmune thyroiditis (Hashimoto's disease). At follow-up thyroid function gradually improved in all but signs of persistent thyroid hypofunction remained in seven. Thus women developing symptomatic postpartum hypothyroidism should be followed regularly and when thyroxine treatment is commenced in the post-partum period, it has to be continued indefinitely in many cases.

Two women presented with transient low radioiodine uptake thyrotoxicosis and a small painless goitre. Thyroid cytology revealed thyroiditis but they had no thyroid autoantibodies. When followed after a succeeding delivery none of these women developed post-partum thyroid dysfunction in contrast to women in the autoimmune group. Probably the aetiology of thyroid dysfunction in these 2 women was different.
Effects of neonatal exposure to TRH on development of the pituitary-thyroid axis in rats
Authors: Kawai Yoshiaki , Azukizawa Mizuo , Ashida Nobuyuki , Kumahara Yuichi , Miyai Kiyoshi
Published: December 2008

Abstract. TRH (10 and 1000 μg/kg body weight) was administered ip daily to neonatal rats from day 0 to 9 after birth (Neo-TRH rats) and their pituitary-thyroid axis was examined on days 4, 10, 21 and 90. The pituitary TSH content in Neo-TRH rats was significantly smaller than in controls on days 4 and 10. The serum TSH levels in Neo-TRH rats were significantly lower than those in controls on days 4 (male group only), 10 and 21 (only 10 μg/kg group).

The serum T4 levels in Neo-TRH rats were lower than in controls on day 10. The reduced pituitary TSH content and serum TSH and T4 were restored to control levels on day 90. However, the response of serum TSH to exogenous TRH (10 μg/kg/ip) was blunted in Neo-TRH rats on days 10, 21 and 90. It is concluded that repetitive administration of TRH during the neonatal period suppresses the pituitary-thyroid axis in neonatal life, even after the basal hormone level has been restored to normal.
Familial hypocalciuric hypercalcaemia: observations on vitamin D metabolism and parathyroid function
Authors: Davies M. , Adams P. H. , Berry J. L. , Lumb G. A. , Klimiuk P. S. , Mawer E. B. , Wain D.
Published: December 2008

Abstract. Serum vitamin D metabolites, the renal tubular maximum reabsorptive rate for phosphate (TMP/GFR) nephrogenic cyclic AMP (NcAMPI, and CaE (urinary calcium excretion per litre of glomerular filtrate) were measured in 14 adults with familial hypocalciuric hypercalcaemia (FHH). The findings were compared with analyses in 14 patients with surgically proven primary hyperparathyroidism matched for serum calcium, creatinine clearance and vitamin D status (assessed by serum concentrations of 25 hydroxyvitamin D). Vitamin D metabolites were also measured in 16 normocalcaemic relatives of patients with FHH. The serum concentration of 24, 25 dihydroxycholecalciferol was appropriate for the prevailing 25 hydroxyvitamin D and no difference was found between groups. The serum concentration of 1, 25 dihydroxycholecalciferol was significantly greater in primary hyperparathyroidism (P < 0.0005) compared with patients with FHH and their normocalcaemic relatives. TMP/GFR was reduced in both primary hyperparathyroidism (0.53 ± 0.12 mmol/l GF, mean ± sem) and FHH (0.86 ±0.14 mmol/l GF). Patients with primary hyperparathyroidism showed an increase in NcAMP output in the urine (38.5 ± 16 mmol/l GF) which was significantly greater (P < 0.0001) than the normal NcAMP (13.5 ± 9.2 nmol/l GF) found in FHH. CaE was low in FHH indicating increased renal tubular reabsorption of calcium.

It is concluded that there is no abnormality of vitamin D metabolism in FHH comparable with the changes observed in primary hyperparathyroidism. It is suggested that the biochemical abnormalities in FHH cannot be explained solely upon an increased sensitivity of the renal tubules to the effects of endogenous parathyroid hormone.
Changes in pituitary secretion induced by an agonist-antagonist opioid drug, buprenorphine
Authors: Rolandi Ermanno , Marabini Alessandra , Franceschini Roberto , Messina Valeria , Bongera Patrizia , Barreca Tommaso
Published: December 2008

Abstract. The im administration in 6 healthy subjects of buprenorphine, a derivative of the morphine alkaloid thebaine with agonist-antagonist properties, resulted in a significant rise of serum Prl within 45–240 min, a small and transient increase in serum GH and a significant fall in serum cortisol values. Conversely, no appreciable changes in the serum levels of the other hormones studied were found. The observed hormonal effects indicate that, in man, buprenorphine exerts an opiate agonist rather than an opiate antagonist effect.
Effect of pre-treatment of long-term ovariectomized rats with anti-LRH on the response of the pituitary gland in vitro to the analogue of LRH D-ser-(tBu)6-des-gly10-ethylamide-LRH (Buserelin®)
Authors: van Rees G. P. , van Dieten J. A. M. J. , de Koning J. , de Goey A. F. P. M.
Published: December 2008

Abstract. Ovariectomized rats were injected iv with an antiserum against LRH or normal rabbit serum. AntiLRH caused a decrease of plasma LH and FSH. After 24 or 48 h, the rats were decapitated and the pituitary glands incubated in the presence of an analogue of LRH which reacts minimally with anti-LRH (Buserelin). Pretreatment with anti-LRH caused an increased response of pituitary LH release to Buserelin. Similar results were obtained with regard to FSH. In this case, however, basal release of FSH was lowered by pre-treatment with antiLRH. Pituitary LH and FSH contents were not affected by anti-LRH, but synthesis of LH and FSH in vitro was smaller than in control glands obtained from rats pretreated with normal rabbit serum.
Immunoreactive thyroglobulin-like material derived from saliva
Authors: Shah D. H. , Dandekar S. R. , Jeevanram R. K. , Thakare U. R. , Ajaykumar B. S. , Ganatra R. D.
Published: December 2008

Abstract. The presence of an immunoreactive thyroglobulin-like material in saliva from normal subjects and from 35 patients with thyroid carcinoma was detected by radioimmunoassay. The levels of this material in saliva were markedly elevated in patients with extensive metastases.

Concentrated saliva samples from normal subjects and from patients with thyroid carcinoma were fractioned on Sepharose-6B and each fraction was assayed for thyroglobulin content by RIA. Several protein peaks of varying molecular size with thyroglublin-like immunoreactivity were observed. The physiological significance of these molecules in saliva remains to be established.
Immunoreactive thyrotrophin-releasing hormone like material (IR-TRH LM) in human cord blood: high circulating serum levels but possible non-identity with hypothalamic TRH
Authors: Kaufman J. M. , Elewaut A. , Vermeulen A.
Published: December 2008

Abstract. Levels of immunoreactive thyrotrophin-releasing hormone like material (IR-TRH LM) were measured in paired maternal and umbilical cord serum samples (n = 45) and in serum of non-pregnant women (n = 63), using a sensitive and specific radioimmunoassay.

In all pairs IR-TRH LM in venous cord serum (mean 91.3 pg/ml, range 20–270) was markedly elevated as compared to maternal serum (mean 13.5 pg/ml, range 0–37, P < 0.001, the maternal levels being similar to those in non-pregnant women (mean 12.0 pg/ml, range 0–39, P > 0.1). In 23 cases IR-TRH LM was also measured in arterial cord serum: arterial and venous cord levels were highly significantly correlated (r = 0.904) with higher arterial levels in 22 out of 23 cases (mean 117.8 pg/ml, range 32–280 and 90.6 pg/ml, range 20–270, P < 0.001), suggesting that cord IR-TRH LM is not of placental origin. There was no correlation between individual levels of IR-TRH LM and either TSH, T4, T3 or FT4 levels in either maternal or cord serum.

Agar gel electrophoresis and equilibrium dialysis of adult and cord serum pre-incubated with [125I]TRH or [3H]TRH revealed no protein binding. Cord IR-TRH LM was immunologically, as well as in paper electrophoresis and in gelfiltration, indistinguishable from synthetic and hypothalamic TRH.

In vitro degradation of synthetic TRH was much slower in cord serum as compared to maternal and control serum (P < 0.001). In vitro degradation of cord IRTRH LM could not be demonstrated, neither by cord serum itself nor by adult serum, this in contrast to hypothalamus extracted TRH which was readily degraded by adult serum. Neither the presence of an inhibiting substance, nor methodological factors seem to account for the apparently different behaviour of cord IR-TRH. It is suggested that circulating IR-TRH could be closely related, but still different from tissue extracted and synthetic TRH.
Synthetic [Asu1,7] eel calcitonin increases phosphorus content in the hepatic mitochondria of rats
Authors: Yamaguchi Masayoshi
Published: December 2008

Abstract. The change of subcellular phosphorus content in the liver was investigated after a single sc administration of synthetic [Asu1,7] eel calcitonin (CT) to fed rats. Administration of CT (80 MRC mU/100 g body weight) produced a significant increase in phosphorus content in the mitochondrial fraction, while this increase was not observed in fractions containing plasma membrane, nuclei, microsomes and cytosol. A significant increase in the mitochondrial phosphorus content was observed even at the lowest dose of CT (40 MRC mU/100 g body weight). A single ip administration of 2,4-dinitrophenol (0.1 mg/100 g body weight), an inhibitor of oxidative phosphorylation, did not prevent significant increases in phosphorus contents of the homogenate and the mitochondria caused by administration of CT (80 MRC mU/100 g body weight), although the drug markedly inhibited ATPase activity in the mitochondria. Administration of CT did not produce a significant alteration in the mictochondrial ATPase activity. These results suggest that phosphorus taken up by the liver cells after CT administration is largely located in the mitochondria, and that this increase is not related to oxidative phosphorylation. Presumably the hepatic mitochondria play a role in the storage of intracellular phosphorus increased by CT.
Induction of ovulation by prolonged pulsatile administration of luteinizing hormone releasing hormone (LRH) in patients with clomiphene resistant polycystic ovary-like disease
Authors: Burger C. W. , van Kessel H. , Schoemaker J.
Published: December 2008

Abstract. Induction of ovulation with pulsatile administration of LRH by automatic portable infusion pump for 74 and 147 consecutive days in 2 patients with clomiphene resistant PCO-like disease is described. The patients exhibited 6 ovulatory cycles. One patient conceived during the fourth cycle. During the treatment a unilocular cyst, probably a lutein cyst, developed in one patient, but subsequently disappeared spontaneously under uninterrupted therapy. No chemical hyperstimulation was observed. Follicular phases lasted for 32 and 13 days in patient I and for 19, 25, 14 and 22 days in patient II. Luteal phases lasted for 16 and 15 days in patient I and for 17, 18 and 15 days, respectively in patient II. Total urinary oestrogen and pregnanediol excretion did not differ from that seen in normal cycles. LH baseline and peak values and LH responses declined to normal levels accompanied by a normalization of the LH/FSH ratio during pulsatile LRH treatment in both patients. The first pre-ovulatory episode occurred already after partial normalization of the LH/FSH ratio. The endocrinology of the second LRH induced cycles of patients I and II was not different from cycles similarly induced in hypogonadotrophic patients. We conclude that ovulation induction with pulsatile LRH administration in patients with clomiphene resistant PCO-like disease is possible. Our findings give hope that this mode of treatment may not only be effective, but may prove to be safer than ovulation induction with menopausal gonadotrophins in patients with clomiphene resistant PCO-like disease.
Sex-hormone-binding globulin (SHBG) in serum in threatened abortion
Authors: Hertz J. B. , Johnsen S. G.
Published: December 2008

Abstract. The binding capacity of the sex-hormone-binding globulin (SHBG) was determined by means of a new dihydrotestosterone-binding-capacity test in 73 pregnant women admitted to hospital because of vaginal bleeding between the 6th and 18th gestational week. In general, pregnancies ending in spontaneous abortion displayed lower SHBG-levels than pregnancies with a successful outcome, but a great deal of overlap in SHBG values was found between the abortive and the non-abortive cases. In the 6th to 9th weeks of pregnancy 'non-pregnant' SHBG levels were frequently found despite normal levels of oestradiol (E2) in patients continuing pregnancy until delivery. After the 9th gestational week a highly significant positive correlation was found between E2 and SHBG. The lack of correlation between these parameters before this gestational age indicates that the increased SHBG synthesis seen in pregnancy develops later than the rise in E2. Determinations of SHBG were found to be of limited value in evaluation of the prognosis is threatened abortion.
Isolated ACTH deficiency accompanied by 'primary hypothyroidism' and hyperprolactinaemia
Authors: Yoshida Tadayoshi , Arai Tetsuya , Sugano Jinpei , Yarita Hiroshi , Yanagisawa Hideo
Published: December 2008

Abstract. A 55 year old man with isolated ACTH deficiency is reported. The lesion would appear to be located in the pituitary gland since plasma ACTH and cortisol did not respond to lysine vasopressin and corticotrophin releasing factor (CRF). A fall in T4, a rise in basal values of TSH, prolactin (Prl), LH and FSH, excessive responses of TSH and Prl to TRH, and hyperreactive responses of LH and FSH to LRH were observed. These hormonal changes were examined before and after administration of cortisol. The abnormality in these hormones might be caused by deficiency of long-term glucocorticoid.
A comparison of diagnostic methods to differentiate diabetes insipidus from primary polyuria: a review of 21 patients
Authors: Milles J. J. , Spruce Barbara , Baylis P. H.
Published: December 2008

Abstract. Direct measurement of plasma AVP and indirect assessment of antidiuretic activity during standard dehydration tests were made in 21 polyuric and polydipsic paients to establish the efficacy of each method in determining the cause of polyuria. Patients with acquired nephrogenic diabetes insipidus (e.g. diabetes mellitus, renal failure, hypercalcaemia) were excluded from the study. Cranial diabetes insipidus was diagnosed by plasma AVP responses to osmotic stimulation during infusion of hypertonic 5% saline which were subnormal in 13 patients, 4 of whom had undetectable plasma AVP and 3 who had reduced but osmoregulated AVP release. Standard water deprivation tests confirmed cranial diabetes insipidus in all but 2 patients who were diagnosed as partial nephrogenic diabetes insipidus. The remaining 8 patients had normal, osmoregulated AVP secretion; the cause of their polyuria was determined by their renal response to desmopressin. Two patients had nephrogenic diabetes insipidus and 6 had primary polydipsia. The majority of polyuric patients could be accurately diagnosed by carefully performed dehydration tests. We suggest that direct measurements of plasma AVP during osmotic stimulation are only necessary to distinguish mild forms of cranial from nephrogenic diabetes, or to define precisely the characteristics of AVP secretion.
β-Neoendorphin inhibits thyrotrophin secretion in rats
Authors: Mitsuma Terunori , Nogimori Tsuyoshi
Published: December 2008

Abstract. The effects of β-neoendorphin on thyrotrophin-releasing hormone (TRH) and thyrotrophin (TSH) secretion in rats were studied. β-neoendorphin (500 μg/kg) was injected iv, and the rats were decapitated serially. TRH, TSH, thyroxine (T4) and 3,3',5-triiodothyronine (T3) were measured by means of a specific radioimmunoassay for each.

Hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after β-neoendorphin injection, and plasma concentrations tended to decrease, but not significantly so. Plasma TSH levels decreased significantly in a dose-related manner with a nadir at 40 min. Plasma T4 and T3 levels did not change after the injection. Plasma ir-TRH and TSH responses to cold were significantly inhibited by β-neoendorphin, but the plasma TSH response to TRH was not. Naloxone partially prevented the inhibitory effect of β-neoendorphin on TSH release. In the haloperidol- or 5-hydroxytryptophan-pretreated group, the inhibitory effect of β-neoendorphin on TSH release was prevented, but not in the l-dopa- or para-chlorophenylalanine-pretreated group. These drugs alone did not affect plasma TSH levels at the dose used.

These findings suggest that β-neoendorphin acts on the hypothalamus by inhibiting TRH release, which may be modified by amines of the central nervous system.
Increased frequency of HLA-Cw4 in type 2 diabetes
Authors: Groop L. , Koskimies S. , Pelkonen R. , Tolppanen E.-M.
Published: December 2008

Abstract. In order to investigate whether there is an association between the HLA system and type 2 diabetes, we have determined HLA-A, B- and C-antigens in 227 patients with onset of diabetes between the ages of 35 and 70 years and compared them with the HLA-antigen frequencies in Finnish blood donors.

One hundred and sixty-eight patients (74%) were treated with diet or oral antidiabetic drugs (non-insulin dependent), whereas 59 patients (26%) were treated with insulin (insulin-dependent).

The HLA-antigen Cw4 was found in 38.7% of the non-insulin dependent patients (relative risk 2.67, P = 0.00005) and in 15.6% of the insulin dependent diabetics (relative risk 0.785 NS) compared with 19.1% in blood donors. In addition, there was an increase in the frequency of HLA-Bw35 antigen among the non-insulin dependent patients (relative risk 1.6, P = 0.007), which could be explained by the known positive linkage disequilibrium between HLA-Bw35 and HLA-Cw4.

In insulin-dependent patients there was a decrease in the frequency of HLA-B7 (relative risk 0.226, P = 0.001) and an increase in the frequencies of HLA-B8 (relative risk 1.91, P = 0.031), B12 (relative risk 2.22, P = 0.01) and B15 (relative risk 2.04, P = 0.019) compared with blood donors.

Conclusion: these data provide evidence that genes in the HLA region may have some influence in genetic susceptibility to type 2 diabetes. They further suggest that maturity onset (type 2) diabetes is a heterogeneous disease in terms of HLA antigens. Consequently, there is a need for re-evaluation of the definition of type 2 diabetes.
Normal somatomedin-C/insulin-like growth factor I binding and action in cultured human fibroblasts from Turner syndrome
Authors: Rosenfeld Ron G. , Dollar Laura A. , Hintz Raymond L. , Conover Cheryl
Published: December 2008

Abstract. Growth retardation is a major manifestation of Turner syndrome (TS). Since plasma growth hormone and somatomedin-C/insulin-like growth factor I (SM-C/IGF-I) levels are generally normal, growth failure has been ascribed to peripheral defects in SM-C/IGF-I receptors or action. We have measured the binding of [125I]SM-C/IGF-I to cultured fibroblast monolayers derived from patients with Turner syndrome, and have evaluated SM-C/IGF-I stimulation of both [3H]thymidine incorporation and cell replication. When compared to fibroblasts from normal adults, newborns, and agematched children, no significant differences were observed in specific binding of [125I]SM-C/IGF-I to fibroblast monolayers, and displacement curves demonstrated similar receptor affinities for all groups. Similarly, equivalent SM-C/IGF-I stimulation of [3H]thymidine incorporation was seen in both Turner and control fibroblasts. In the absence of serum, SM-C/IGF-I, at a concentration of 10–25 ng/ml, stimulated thymidine incorporation 3.7–11.8-fold in Turner fibroblasts and 1.9–9.8-fold in control cells. In combination with 1.0% human hypopituitary serum (HHS), SM-C/IGF-I stimulated thymidine incorporation 20–70-fold in all cell lines. Cell replication in both TS and control cells was increased 90% by the combination of SM-C/IGF-I + 0.5% HHS, and 140% by SM-C/IGF-I + 0.5% HHS + dexamethasone. We conclude that TS fibroblasts have normal SM-C/IGF-I receptors and sensitivity, and are capable of enhanced DNA synthesis and replication following SM-C/IGF-I stimulation.
Aggression-provoked huge release of submaxillary mouse renin to saliva
Authors: Pedersen Erik Bækkelund , Poulsen Knud
Published: December 2008

Abstract. In a normal male mouse, which had been kept isolated for some time, confrontation with another male mouse, resulted in aggressive behaviour, including fighting. The aggressive behaviour resulted in secretion of a few microlitre of saliva with vast renin concentration. The renin concentration in saliva reached values of 6000 Goldblatt units × ml−1, corresponding to 15 mg/ml of renin. This concentration is 6 orders of magnitude higher than normal plasma renin concentrations. The secretory pattern could be mimicked by ip injection of pharmacological doses (2–18 mg/kg) of the α-adrenergic agonist phenylephrine.

This is probably the first demonstration of a physiological secretion of renin to saliva which may be of importance since renin most likely is injected into the opponent or prey through bites.
Prolactin secretion from human prolactinomas perifused in vitro: effect of TRH, prostaglandin E1, theophylline, dopamine and dopamine receptor blockers
Authors: Chihara Kazuo , Iwasaki Junji , Minamitani Naoto , Kaji Hidesuke , Kodama Hitoshi , Fujita Takuo , Shirataki Kunio , Tamaki Norihiko , Matsumoto Satoshi
Published: December 2008

Abstract. To clarify the functional characteristics of prolactin (Prl)-producing adenoma cells, the effect of TRH, prostaglandin E1 (PGE1), theophylline, dopamine and dopaminergic antagonists on Prl secretion was examined in vitro in perifused pituitary adenoma tissues obtained at surgery from 8 patients with prolactinoma. Perifusion with TRH at a concentration of 10−6 to 10−5 m resulted in a significant increase in effluent Prl levels in 3 of the 8 adenoma tissues. In the remaining 5 adenomas, TRH produced no effect on Prl release in vitro. On the other hand, PGE1 (10−5 m) stimulated Prl secretion in 2 of the 4 adenomas examined. Addition of theophylline (5.5 mm) caused a marked increase of effluent Prl levels in all 8 prolactinomas regardless of the reactivity to TRH or PGE1.

Dopamine (5 × 10−7 m) suppressed Prl secretion from adenoma tissue in 5 of 7 patients tested but had no effect in the remaining two adenomas. When perifused simultaneously with dopamine, sulpiride (D2-selective dopamine receptor blocker, 5 × 10−7 m) blocked the inhibitory effect of dopamine on Prl release in 3 of the 4 dopamine-sensitive prolactinomas. In one adenoma responsive to dopamine but resistant to sulpiride, YM-09151-2 (relatively specific D1-dopamine receptor blocker, 5 × 10−7 m) antagonized the dopaminergic inhibition of Prl release. When perifused alone, neither sulpiride nor YM-09151-2 affected Prl release from any of the adenoma tissues tested.

These findings suggest that a direct action of TRH on the adenoma cells in stimulating Prl release may be lacking in some prolactinoma cells, and that quantitative and qualitative changes in the dopaminergic inhibition of Prl release may occur in some adenomatous lactotrophs.
Vascularization and iodide transport down regulation in rat goitre
Authors: Rognoni J. B. , Penel C. , Ducret F.
Published: December 2008

Abstract. This study was designed to investigate, in the rat, the regulation of the amount of thyroid iodide and of its organification during the involution of an experimentally induced goitre. The goitre was obtained by drastic iodine deficiency; male Wistar rats received an iodide deficient diet for 6 months, supplemented with PTU during the last 2 months. The study was followed for 16 days after the beginning of iodide refeeding (daily iodine intake = 50 μg).

The thyroid iodide, total thyroid organic iodine and plasma iodide, PBI and TSH concentrations were determined from day 0 to 16 and compared to their control values (rats on a normal iodide diet for 6 months). In addition, a stereological study was carried out to determine if the extent of the gland vasculature might be implicated in the regulation of the thyroid iodide content.

The plasma TSH concentration was very high and constant for 8 days (2.40 ± 0.37 and 2.45 ± 0.43 on day 0 and 8 respectively vs 0.25 ± 0.12 μg/ml in control rats), whereas iodination and secretion were blocked for 4 days (0.34 ± 0.19 and 0.5 ± 0.1 on day 0 and 4 respectively vs 14.4 ± 2.0 μg 127I/gland in control rats) (Wolff-Chaikoff effect). Thyroid iodide amount increased enormously for 2 days (2.5 ± 0.6 and 2.45 ± 0.55 respectively on day 1 and 2 vs 0.09 ± 0.01 μg 127I/gland on day 0), then strongly decreased between 2 and 4 days (1.15 ± 0.27 127I/gland). The thyroid/serum (T/S) ratio (iodide pump), which was very important between 0 and 2 days (115), decreased strikingly on day 4 (55). Moreover, the thyroid homogenates were shown to contain a new (nonproteic) iodocompound which escaped classical iodination. Its mobility during polyacrylamide gel electrophoresis was intermediary between those of iodoaminoacids and iodide. Its turnover rate was practically similar to that of thyroid iodide. This compound (termed 'X') accumulated until day 2 (0.39 ± 0.03 μg 127I/gland), then decreased sharply as did thyroid iodide, whereas neoiodination resumed (Wolff-Chaikoff escape). The stereological results showed that as soon as the iodide refeeding started, the volume density as well as the surface density of vessels sharply decreased (0.23 ± 0.03 μm3/μm3 and 0.06 ± 0.03 μm2/μm3 on day 0 and 8, respectively), whereas the same parameters for thyroid epithelial cells remained constant (0.35 ± 0.02 μm3/μm3 and 0.32 ± 0.03 μm2/μm3 on day 0 and 8, respectively.

From these data we can conclude that a great iodide influx in hyperstimulated thyroid epithelial cells induces a cellular control, antagonist to the TSH action on the amount of thyroid iodide. This control acts sequentially: an early regression of the thyroid vasculature is observed, which is followed by a regulation of iodide active transport. The 'X' iodocompound might be one of the factors implicated in this control.
Changes in the multiple components of rat pituitary TSH and TSHβ subunit following thyroidectomy
Authors: Mori Masatomo , Ohshima Kihachi , Fukuda Hitoshi , Kobayashi Isao , Wakabayashi Katsumi
Published: December 2008

Abstract. Heterogeneity of pituitary TSH was investigated in rats following thyroidectomy. Adult male rats were sacrificed at varying periods (2–28 days) after thyroidectomy. In another experiment, thyroidectomized rats were injected daily with various doses of l-T4 (0.3–7.5 μg/100 g body weight, ip) and sacrificed 2 weeks later. The homogenate of the pituitaries was applied on an isoelectric focusing column or a Sephacryl S-200 column.

The normal rat pituitary contained 5 major components of immunoreactive (IR) TSH in isoelectric focusing, in which the isoelectric point (pi) ranged from 6.6 to 8.8. The multiple components of IR-TSGβ were observed almost in the same areas as those of IR-TSH. Following thyroidectomy IR-TSH components with more acidic pI, associated with IR-TSHβ, were evident. A large amount of IR-TSHβ in the pituitaries of thyroidectomized rats appeared near the void volume in gel filtration, suggesting the presence of big TSHβ Supplement of l-T4 minimized these thyroidectomy-induced changes in isoelectric focusing and gel filtration. Furthermore, big IR-TSHβ was little affected by ultracentrifugation and was relatively stable after treatment with 6 m guanidine hydrochloride.

We demonstrated that the rat pituitary gland contained multiple components of IR-TSH and IR-TSHβ, both of which became variegated after thyroidectomy. It is suggested that a discernible degree of heterogeneity of TSH, particularly of TSHβ, is dependent upon the increased rate of TSH biosynthesis at the pituitary level.
Effects of α1-, α2- and β-adrenoceptor blockers on insulin secretion in the rat
Authors: Ahrén Bo , Lundquist Ingmar , Järhult Johannes
Published: December 2008

Abstract. The effects of α- and β-adrenoceptor blockade on plasma concentrations of insulin and glucose were studied in the anaesthetized rat. Infusion of the α1-adrenoceptor blocker prazocin (80 μg/min), the α2-adrenoceptor blocker yohimbine (15 μg/min) or the non-selective α-adrenoceptor blocker phentolamine (15 μg/min) during 50 min increased plasma insulin levels by about 1.5–2.5 ng/ml. The effects of phentolamine and prazosin on circulating insulin persisted throughout the infusion whereas the effect of yohimbine seemed to be more transient. Plasma glucose levels increased slightly during infusion of prazosin, but tended to decrease in response to phentolamine and yohimbine. The β-adrenoceptor blocker propranolol (15 μg/min) lowered basal plasma insulin and glucose levels. It also depressed plasma insulin during infusion of all three α-adrenoceptor blockers without any appreciable influence on plasma glucose. It is suggested that both α1- and α2-adrenoceptor as well as β-adrenoceptors are involved in the regulation of basal insulin secretion in the rat.
In vitro lymphocyte recognition of islet cells following in vivo priming with allogeneic murine pancreatic islets
Authors: Scott Joanne , MacKay Peter G. , Lernmark Åke
Published: December 2008

Abstract. Lymphocytes from patients with insulin-dependent diabetes have been shown to be sensitized to pancreatic tissue antigens. Mice immunized with homologous pancreatic islets have been found to develop glucose intolerance and insulitis. Since lymphocytes may be involved in diabetogenesis, we wished to determine if lymph node cells from islet-immunized mice can recognize and respond to islet cells in vitro.

A.TL female mice were immunized with an emulsion of BALB/c islet homogenate and complete Freund's adjuvant (CFA); sham-treated A.TL mice were injected with adjuvant and water. Mice were sacrificed 7–8 days later and the draining lymph nodes were removed. The lymph node cells were co-cultured with freshly prepared irradiated BALB/c islet cell, which served as stimulator cells. The co-cultures were incubated for 24–26 h at 37°C, followed by a 16 h [3H]thymidine (TdR) pulse.

A significant proliferation of lymph node cells from islet-primed mice was induced during the in vitro stimulation with irradiated islet cells when compared with lymph node cells from sham-treated mice (P < 0.001). The response may be islet-cell-specific, since irradiated lymph node cells from BALB/c mice failed to proliferative response under the same culture conditions (P > 0.80).
Prolactin secretion in polycystic ovary syndrome (PCO): correlation with the steroid pattern
Authors: Carmina Enrico , Rosato Francesca , Maggiore Michele , Gagliano Anna Maria , Indovina Daniela , Jannì Alberto
Published: December 2008

Abstract. To evaluate the prevalence of hyperprolactinaemia in PCO patients and its possible correlation with a steroid pattern, we studied prolactin secretion (basal and after TRH stimulation) in 40 women affected by typical PCO. LH, FSH, testosterone, oestradiol, oestrone, DHEA-s and 17-OHP serum levels were also evaluated. Twenty-one patients had prolactin (Prl) values in the normal range both in baseline conditions and after TRH stimulation; 10 patients had normal basal values of Prl but an exaggerated response to TRH stimulation; 9 patients had high Prl basal values and an exaggerated response to TRH. The presence of hyperprolactinaemia was associated with increased serum levels of oestrone (P < 0.01), DHEA-s (P < 0.01) and 17-OHP (P < 0.05).

In conclusion, hyperprolactinaemia is as relatively frequent condition which affects almost half the patients suffering from PCO and is probably related to an increase of serum oestrogens, mostly oestrone. Moreover, in patients with PCO and hyperprolactinaemia, the production of some other steroids is also affected.
Relationship between thyroid volume and serum thyroglobulin during long-term suppression with triiodothyronine in patients with diffuse non-toxic goitre
Authors: Feldt-Rasmussen Ulla , Hegedüs Laszlo , Hansen Jens M. , Perrild Hans
Published: December 2008

Abstract. Twenty-five patients with non-toxic diffuse goitre were studied during and after 12 months of treatment with 60 μg triiodothyronine daily in order to see whether a correlation could be found between the reductions of thyroid volume, using ultrasonic scanning, and serum thyroglobulin. Thyroid function tests and thyroid volume determination were performed before treatment and after 3, 6 and 12 months of therapy in 19 patients (group 1). In patients of group 2 (n = 19) the same tests were performed at the end of 12 months treatment and 6 and 12 months after withdrawal. Before treatment all patients had a significantly increased thyroid volume compared to controls matched according to sex, age and body weight (P < 0.001). Serum thyroglobulin was elevated compared to controls (P < 0.02), with a significantly positive correlation to the thyroid volume (Spearmann's Rho = 0.52, P < 0.02). Both serum thyroglobulin and thyroid volume decreased during treatment in the majority of the patients, concomitantly in approximately half of them. After withdrawal of treatment (group 2) serum thyroglobulin showed a median increase of 54% after 6 months and remained unchanged thereafter, whereas the thyroid volume was unchanged after 6 months. These findings might support the concept that the regulation of thyroid growth and of protein synthesis and degradation might be determined by different factors.