bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered balance of immunoregulatory T lymphocyte subsets in autoimmune thyroid diseases
Authors: Misaki Takashi , Konishi Junji , Iida Yasuhiro , Endo Keigo , Torizuka Kanji
Published: December 2008

Abstract. Three monoclonal antibodies recognizing cell surface antigens of total peripheral (OKT3), helper/inducer (OKT4) and suppressor/cytotoxic (OKT8) T lymphocytes were used by an indirect immunofluorescence technique to enumerate peripheral T lymphocytes in 25 patients with Graves' disease (including 4 euthyroid Graves' patients), 16 patients with Hashimoto's thyroiditis and 22 normal controls. Total lymphocyte count and percentages of overall T and helper/inducer T cells among peripheral lymphocytes in these conditions showed no significant difference from those of the controls. Percentage of suppressor/cytotoxic T cells, however, was decreased in Graves' disease patients with or without hyperthyroidism. The ratio of helper/inducer T cells to suppressor/cytotoxic T cells was increased in Graves' disease population and slightly increased in hypothyroid Hashimoto's thyroiditis patients. The ratio correlated with the mitogenic response of peripheral mononuclear cells to phytohaemagglutinin, but not with the serum levels of thyroid hormones nor with the titres of thyroid autoantibodies. These findings are in accordance with the results of previous functional studies and indicate possible defects in suppressor T lymphocytes in autoimmune thyroid disease.
The effect of d,l-4-hydroxypropranolol on the thyroxine to 3,5,3'-triiodothyronine conversion in rat renal and liver microsomes
Authors: Jørgensen Preben Holme , Lumholtz lb Bo , Faber Jens , Kirkegaard Carsten , Siersbæk-Nielsen Kaj , Friis Thorkild
Published: December 2008

Abstract. The in vitro effect of d,l-4-hydroxypropranolol, a major pharmacological active metabolite of the beta adrenoceptor blocking drug d,l-propranolol, on the thyroxine (T4) to 3,5,3'-triiodothyronine (T3) conversion has been studied using rat renal and liver microsomal fractions. The results showed, that primarily the metabolite, but also the parent drug inhibits the T3-production in a dose dependent manner. The potency, expressed as the 50% inhibition of the T3-production, was reached using 65 ± 12 (sd) μm d,l-4-OH-propranolol and 1000 ± 22 (sd) μm d,l-propranolol, respectively in both tissues. The efficacy of 4-OH-propranolol corresponded to a maximal inhibition of 86 ± 7% while it for d,l-propranolol corresponded to 58 ± 6% (P < 0.001). The beta adrenoceptor agonist isoprenaline itself did not effect the T4 to T3 conversion but considerably opposed the inhibitory effect of d,l-4-OH-propranolol but not of d,l-propranolol. The D-isomer form of propranolol, which is without beta receptor blocking activity inhibited the T3-production in the same degree as d,l-propranolol. Evaluation of the enzyme kinetic data suggested that 4-OH-propranolol caused a competitive inhibition of both T4 and DTT.

It is concluded, that the metabolite d,l-4-OH-propranolol is a much more potent and efficacious inhibitor of the T4-5'-deiodination than d,l-propranolol.
Absorption of soluble and isophane semi-synthetic human and porcine insulin in insulin-dependent diabetic subjects
Authors: Pramming Stig , Lauritzen Torsten , Thorsteinsson Birger , Johansen Klaus , Binder Christian
Published: December 2008

Abstract. A double-blind cross-over study of the sc absorption of radiolabelled semi-synthetic human (SHI) and purified porcine (PPI) insulin was made. Absorption of both isophane (n = 10) and soluble insulin (n = 8) was studied. There was no significant difference between the disappearance from the injection site, the plasma free insulin concentrations, or blood glucose levels after sc injection of the isophane preparations.

A faster disappearance of the soluble SHI (as judged from T/50 and AUC) was found (both P-values < 0.01). However, no difference was observed between the plasma insulin concentrations at any time point (P < 0.05). Blood glucose levels showed no statistical differences between the two soluble preparations. The data indicate minor differences between the pharmaco-kinetics of SHI and PPI, but these seem of no clinical importance.
Potassium homeostasis in chronic experimental diabetes mellitus in rats
Authors: Hayashi Matsuhiko , Senba Shigetoshi , Saito Ikuo , Kitajima Waichi , Saruta Takao
Published: December 2008

Abstract. To examine potassium homeostasis in diabetes mellitus, we observed the effect of dietary potassium loading on the renin-angiotensin-aldosterone system and potassium balance in streptozotocin-induced diabetic rats. In diabetic rats with 26.51 ± 1.89 mmol/l of serum glucose, the plasma renin activity (PRA), plasma aldosterone (PA), immunoreactive insulin (IRI) and urinary excretion of prostaglandin E2 (PGE2) were all significantly lower than in control rats, but the plasma potassium and renal function were not significantly different. With potassium loading, both control and diabetic rats showed a similar increase in plasma potassium and urinary potassium excretion and a decrease in PRA, but the IRI, plasma corticosterone and urinary excretion of PGE2 exhibited no significant change. On the other hand, the PA was significantly increased only in the control rats, and not in the diabetic rats on potassium loading. Based up on these results, it is suggested that potassium homeostasis is well maintained in diabetic rats with normal renal function in spite of an attenuated response of aldosterone secretion to dietary potassium loading and insulin deficiency.
Effects of an acute calcium load on plasma ACTH, cortisol, aldosterone and renin activity in man
Authors: Isaac Roland , Raymond Jean-Paul , Rainfray Muriel , Ardaillou Raymond
Published: December 2008

Abstract. Plasma adrenocorticotrophin (ACTH), cortisol and aldosterone increased during and after iv administration of calcium gluconate in 4 normal subjects, one patient with hypoparathyroidism and one patient with hypothyroidism. On the other hand, there was a decrease in plasma renin activity but only in the normal subjects. Plasma ACTH and cortisol responses to calcium were abolished whereas plasma aldosterone response persisted in 2 normal subjects pre-treated with dexamethasone. The results observed after calcium administration were compared to those observed after infusion of the solvent only in 6 normal subjects and 4 thyroidectomized patients who were studied twice at 3 day intervals. Plasma ACTH, cortisol and aldosterone were higher when calcium was administered. Plasma renin activity was not statistically different whether or not calcium had been injected in the subjects studied twice. These results demonstrate a direct effect of calcium on ACTH and aldosterone secretion which is not mediated by calcitonin and parathyroid hormone. The stimulatory effect of calcium on cortisol secretion depends on the increase in plasma ACTH.
Ovarian production of progesterone and 20α-dihydroprogesterone in vitro following prostaglandin F2α induced luteolysis in the superluteinized rat
Authors: Torjesen P. A. , Aakvaag A.
Published: December 2008

Abstract. Superluteinized rats were injected with the prostaglandin F2α (PGF2α) analogue cloprostenol to induce luteolysis. The treatment decreased progesterone production of ovarian homogenates from 8.9 ± 0.5 to 4.0 ± 0.7 nmol/ovary/10 min (mean ± sem) within 40 min. tochondrial fractions isolated from control and cloprostenol treated animals produced 4.7 ± 0.4 and 2.8 ± 0.3 nmol progesterone/ovary/10 min, respectively. Thus, the PGF2α analogue treatment significantly reduced mitochondrial progesterone production. Addition of the 15 000 × g supernatant fraction did not influence the progesterone production rates of the mitochondrial fraction. The basal progesterone secretion from quartered ovaries decreased from 1.50 ± 0.15 to 0.38 ± 0.05 nmol/ovary during the initial 15 min of incubation following cloprostenol administration. hCG and N6,O2'-dibutyryladenosine 3':5'-cyclic monophosphate (DBC) stimulated the progesterone secretion from quartered ovaries, but the response was delayed in ovaries obtained from cloprostenol treated animals. Although the response was delayed, the progesterone secretion following cloprostenol treatment was re-activated with cAMP either directly or via hCG. The increment in progesterone secretion above unstimulated controls in response to DBC was not influenced by the cloprostenol treatment while the increment caused by hCG was decreased.

Our data suggest that: 1) PGF2α deactivates mitochondrial progesterone production, 2) this deactivation may be overcome by cAMP, and 3) PGF2α decreases gonadotrophin responsive adenylyl cyclase.
Growth hormone and insulin-like growth factor I in German Shepherd dwarf dogs
Authors: Eigenmann J. E. , Zanesco S. , Arnold U. , Froesch E. R.
Published: December 2008

Abstract. The roles of growth hormone (GH) and insulin-like growth factor I (IGF I) were studied in 9 German Shepherd dwarf dogs. GH deficiency was evidenced in all dogs by an absence of increase in GH levels in response to clonidine administration. While the mean IGF I concentration in normal adult German Shepherds was 280 ± 23 ng/ml and 345 ± 50 ng/ml in immature animals, the mean IGF I concentration in the dwarf dogs was 11 ± 2 ng/ml (mean ± sem, P < 0.001).

In the affected animals, plasma thyroxine (T4) levels were only slightly subnormal and there was an increase in these levels in response to thyroid stimulating hormone (TSH) administration. The findings indicate 1) that dwarfism in German Shepherds is caused by primary GH-deficiency resulting in low circulating levels of IGF I and 2) that IGF I levels in the dog as in man are subject to control by GH.
Uptake, metabolism and subcellular distribution of [125I]T4 in calf thyroid slices
Authors: Chazenbalk G. D. , de Pisarev D. L. Kleiman , Juvenal G. J. , Pisarev M. A.
Published: December 2008

Abstract. Previous work from our laboratory has shown that iodothyronines have a direct inhibitory action on the thyroid. In the present studies the uptake, metabolism and subcellular distribution of labelled thyroxine were analyzed. The entry of this hormone reaches a plateau after 15–20 min incubation and is temperature-dependent. The T/M values for T4 were much lower than those of labelled T3 and the curve was different from that obtained with [125I]. The influence of a series of compounds on the T/M values for thyroxine was studied. KI, T3, IOP PTU and MMI were without effect. Absence of Ca++ in the buffer, or addition of KClO4 or ouabain caused a slight decrease, while TSH produced a stimulation in the T/M ratio. Calf thyroid slices dehalogenated thyroxine, producing both T3 and rT3. TSH increased the generation of these two compounds. Neither PTU nor IOP altered the production of T3 and rT3 significantly. The lack of effect of IOP on T3 and rT3 generation was confirmed in calf thyroid homogenates. However, and in agreement with previous reports, IOP significantly decreased production of both triiodothyronines in rat liver slices and in rat liver homogenates.

When the subcellular distribution of labelled thyroxine was examined most of the radioactivity appeared in the soluble fraction and less than 1 % was present in purified nuclei. The addition of unlabelled thyroxine to the slices only caused a significant displacement in the radioactivity of purified nuclei. The presence of labelled thyroxine in the nuclei was confirmed by paper chromatography.
Insulin resistance in uraemic insulin-dependent diabetics Effect of dialysis therapy as assessed by the artificial endocrine pancreas
Authors: Schmitz O. , Alberti K. G. M. M. , ørskov H.
Published: December 2008

Abstract. Twenty-four hour insulin requirements were measured in 5 uraemic insulin-dependent diabetics using a glucose controlled insulin infusion system (artificial endocrine pancreas). All patients were studied twice: initially 14 (1–27) days before institution of dialysis treatment and again after a mean of 46 (21–98) days on chronic dialysis therapy. At near normal blood glucose level the daily insulin requirements decreased from 44.8 ± 2.9 U pre-dialysis to 35.0 ± 2.3 U post-dialysis (P < 0.001). The reduction included the prandial as well as the basal requirements. Consistent with this, the mean plasma free insulin level was higher pre-dialysis than post-dialysis (42 ± 12μU/ml vs 31 ± 7μU/ml especially during daytime (49 ± 11μU/ml vs 37 ± 9 μU/ml, P < 0.03), suggesting that a decreased insulin degradation was not a major factor in the difference in insulin requirements. The effect of an acute change in azotaemia on insulin requirements was also evaluated in 4 uraemic diabetics on chronic haemodialysis the day prior to and the day after a routine dialysis (serum creatinine 922 ± 59μmol/l vs 555 ± 109μmol/l). No difference in insulin administration on the two days was observed (42.5 ± 6.1 U vs 43.2 ± 5.6 U). It is concluded that insulin resistance is present in uraemic insulin-dependent diabetics analogous to the insulin resistance widely prevalent in non-diabetic uraemic patients. The abnormality is at least partly reversible after several weeks on chronic dialysis, but not acutely. The pathophysiologic mechanisms underlying the insulin resistance in uraemia in the diabetic remain to be clarified.
Purification of the mitochondrial triiodothyronine (T3) receptor from rat liver
Authors: Sterling Kenneth , Campbell Gordon A. , Brenner Milton A.
Published: December 2008

Abstract. The thyroid hormone receptor of the inner membrane of rat liver mitochondria was purified by osmotic and freeze-thaw lyses followed by partial purification on Sephadex G-200, and then by affinity chromatography with T3-Sepharose 4B. A single predominant protein band demonstrable on sodium dodecylsulphate (SDS) polyacrylamide gel electrophoresis was present in the first 4 mm NaOH elution peak of affinity chromatography. This was collected from affinity peaks from about 30 rat livers followed by preparative polyacrylamide gel electrophoresis. A single absorbance peak was observed by high pressure liquid chromatography (HPLC). The purified protein was analyzed for binding constants, amino acid composition, and characterized by analytical ultracentrifugation. The association constant (KA) exceeded 1011 m−1. The sedimentation coefficient (S20,W) was 2.2S, partial specific volume (v) 0.72, frictional coefficient (f/fo)s m 1.68 and the molecular weight was estimated at 28000. The amino acid composition was obtained.
Arginine hydrochloride stimulation of serum potassium and aldosterone is enhanced by somatostatin-28
Authors: Barron Jeffrey L. , Klaff Leslie J. , Levitt Naomi S. , Ling Nicholas , Millar Robert P.
Published: December 2008

Abstract. Potassium, aldosterone and insulin responses to arginine infusion were compared in 5 normal men during infusions of somatostatin-14 (SS-14), somatostatin-28 (SS-28) and a control infusion. SS-14 and SS-28 were infused continuously at a rate of 8.6 pmol/min/kg and arginine (0.5 g/kg) was infused from 30–60 min. Following the control infusion with arginine hydrochloride, serum aldosterone and potassium levels increased slightly. The rise in potassium appears to be due to an exchange of cellular potassium for the proton from the arginine hydrochloride. SS-14 had no significant effect on serum potassium or aldosterone but an equimolar dose of SS-28 significantly enhanced the rise in potassium and aldosterone. SS-28 completely inhibited the arginine-stimulated insulin increase while SS-14 only partially inhibited the insulin increase. Since insulin opposes the increase in serum potassium by stimulating cellular uptake of this cation, the enhanced rise in serum potassium in response to arginine hydrochloride during the SS-28 infusion is likely due to the potent insulin suppressing effect of SS-28. The rise in serum aldosterone is directly related to the degree of elevation of serum potassium. These findings caution against the infusion of SS-28 during an arginine stimulation test.
Effect of oestradiol-17β on uterine epidermal growth factor concentration in immature mice
Authors: Gonzalez F. , Lakshmanan J. , Hoath S. , Fisher D. A.
Published: December 2008

Abstract. Using a specific and sensitive epidermal growth factor radioimmunoassay (EGF-RIA) we have identified EGF in immature mouse uterine tissue. In 16 day old mice a single injection of oestradiol-17β (E2) elicited an increase in uterine wet weight in 24 h but did not affect uterine EGF concentration. Sequential injection of E2 for a 7 day period increased both uterine wet weight and EGF concentration suggesting that change in EGF concentration is a delayed E2 response. The continuous treatment did not alter liver or submandibular gland tissue EGF concentrations, but significantly increased kidney EGF content. These data reveal that both uterine and renal tissue EGF concentrations are subject to modulation by E2 in developing mice.
Failure of valproic acid to inhibit the growth of an ACTH-secreting pituitary adenoma
Authors: Gwinup Grant , Elias Alan N. , Choi Benjamin
Published: December 2008

Abstract. Di-n-propylacetic acid (valproic acid) has been reported to lower plasma ACTH concentration after both acute and chronic administration of the drug. To date, there is no report on the efficacy of the drug in inducing regression of ACTH-secreting pituitary adenomas. We report herein our findings in a patient with Nelson's syndrome who was treated with valproic acid for over a year. Despite a lowering of her plasma ACTH concentration during therapy with valproic acid, the patient's tumour showed no evidence of regression while she was taking the drug. In view of these findings, valproic acid therapy for ACTH-secreting pituitary tumours needs to be re-evaluated.
Antidiuretic effect of perorally administered DDAVP in hydrated humans
Authors: Vilhardt Hans , Bie Peter
Published: December 2008

Abstract. Urine volume and osmolality were measured in volunteers hydrated with drinking water (2% of body weight). During maintained water diuresis DDAVP (1-deamino-8-D-arginine vasopressin) dissolved in water was administered per os. Within 15-30 min a dose-dependent antidiuretic response occurred with a concomitant increase in urine osmolality. Administration of DDAVP through a duodenal tube caused similar antidiuretic effects indicating that the intact peptide can be absorbed from the intestinal mucosa.
Lowering effect of diphenylhydantoin on serum free thyroxine and thyroxine binding globulin (TBG)
Authors: Suzuki Hitoshi , Yamazaki Noriko , Suzuki Yoshinobu , Hiraiwa Masaki , Shimoda Shin-ichi , Mori Katsumi , Miyasaka Matsuei
Published: December 2008

Abstract. To evaluate the effect of anticonvulsants on serum levels of free thyroxine (FT4) and thyroxinebinding globulin (TBG), 32 patients with epilepsy receiving long-term anticonvulsant treatment (mean duration 81.8 ± 8.9 months) were employed in the present study. The serum levels of total thyroxine (TT4), total triiodothyronine (TT3), T3 resin uptake (T3U) and thyrotrophin (TSH) were also measured. Free thyroxine index (FT4I) was calculated from TT4 and T3U. Mean levels of these thyroid function tests were as follows: 5.52 ± 1.51 μg/dl (TT4), 1.16 ± 0.32 ng/dl (FT4), 101.5 ± 16.2 ng/dl (TT3), 27.5 ± 2.6% (T3U), 19.64 ± 3.97 μg/ml (TBG), 1.50 ± 0.36 (FT4I) and 2.21 ± 0.18 μU/ml (TSH). These values except for T3U and TSH were significantly lower than normal values (P < 0.01). Using correlation analysis, a significant dose-dependency (daily doses) was found between diphenylhydantoin (DPH) and TT4, FT4 and TBG. Other anticonvulsants (bartiturates, carbamazepine, primidone) or duration of treatment were not significantly correlated with thyroid function tests. Therefore serum levels of DPH were also measured in 19 out of 32 patients receiving anticonvulsant treatment. Significant negative correlation was found between serum levels of DPH and FT4 (r = −0.65) and DPH and TBG (r = −0.61).
Simple and sensitive method for estimation of antithyroid plasma membrane antibodies in the serum of patients with autoimmune thyroid diseases; comparison with other assays
Authors: Gardas Andrzej , Czarnocka Barbara , Faryna Marta , Adler Grazyna , Lewartowska Alexandra , Krawczyński Krzysztof , Nauman Janusz
Published: December 2008

Abstract. The ability of protein A from Staphylococcus aureus to interact with Fc fragments of IgG was used to estimate the antithyroid plasma membrane antibodies in sera of patients with Graves' disease. The results were expressed as an antithyroid plasma membrane antibodies (ATMA) index. The ATMA index estimated in 60 healthy blood donors varied from 0.57 to 1.28, with a mean value of 0.99, sd Ø 0.20. The ATMA index in hyperthyroid untreated Graves' disease varied from 1.80 to 8.0, with a mean value of 4.7. Autoantibody binding to thyroid plasma membranes could be inhibited by (Fab)2 fragments obtained from the serum of patients with Graves' disease but not by (Fab)2 fragments obtained from the serum of healthy blood donors. The influence of rabbit antithyroglobulin and antimicrosomal antibodies on the ATMA index estimation has been evaluated. The ATMA index estimation was compared with the thyrotrophin binding inhibiting immunoglobulins (TBII) index and with the adenyl cyclase stimulating activity of immunoglobulins obtained from 92 hyperthyroid Graves' patients. The ATMA index was positive in 97%, the TBII index in 62% and TSI in 35% of cases. This method using protein A could also be used for estimation of ATMA in other autoimmune thyroid disorders.
Short-term effect of morphine on the thyroid gland in male rats
Authors: Tal E. , Korányi L. , Kovács Zs. , Endröczi E.
Published: December 2008

Abstract. Experiments were designed to demonstrate that morphine may exert a direct short-term effect on the hormone release of the thyroid gland. Groups of male rats were injected with single doses of 1, 5 and 10 mg/kg morphine, or with 2 mg/kg naloxone and in addition with morphine 30 min after naloxone and/or with naloxone 30 min after morphine pre-treatment. The rats were killed by decapitation 15, 30 and 60 min after the injection and serum was collected and stored for subsequent TSH, T4 and T3 radioassays. All doses of morphine resulted in an increase of serum T4 and T3 concentrations 15 and 30 min after the injection, with a tendency to return to control levels by the 60 min samples. Serum TSH concentrations were to suppressed by administration of 5 and 10 mg/kg but not by 1 mg/kg morphine. Naloxone treatment did not increase the T4 and T3 concentrations; however, serum TSH was elevated in the 15 min sample. Naloxone pre-treatment inhibited the morphine induced release of T4 and T3 into the serum, but naloxone administration after morphine pre-treatment failed to prevent the increase of T4 and T3 secretion. These data suggest that morphine may exert a short-term stimulatory effect on the thyroid gland with a concomitant inhibitory action on the hypothalamo-pituitary TSH system.
Spontaneous in vitro immunoglobulin secretion at the diagnosis of insulin-dependent diabetes
Authors: Papadopoulos Geroge , Petersen Jørgen , Andersen Vagn , Lernmark Åke , Marner Birgitte , Nerup Jørn , Binder Christian
Published: December 2008

Abstract. Blood mononuclear cells obtained from 17 newly diagnosed insulin-dependent diabetic (IDDM) patients treated with insulin for 5 –7 days were assessed for the number of spontaneous and pokeweed mitogen (PWM)-stimulated immunoglobulin-secreting cells in a reverse haemolytic plaque assay. The spontaneous in vitro immunoglobulin secretion was evanescent and decreased in individual patients within 1–4 months of insulin treatment. Compared to matched controls, 53% (9/17) of the IDDM patients had an elevated spontaneous secretion of immunoglobulin, 41% (7/17) for IgG, 35% (6/17) for IgM, and 35% (6/17) for IgA. The quantities of PWM-stimulated IgG, IgM, or IgA secreting cells in IDDM were comparable to the controls. The IDDM patients with spontaneous immunoglobulin secreting cells had higher fasting C-peptide levels compared to the patients with immunoglobulin-producing cells within the normal range (P < 0.05). The average titre of islet cell cytoplasmic antibodies was 1:26 in (9 out of 9 were positive) patients with, compared to 1:1 in patients (4 out of 8 were positive) without spontaneous secretion (P = 0.025). These results suggest that the clinical onset of IDDM is associated with a polyclonal B lymphocyte activation and that higher levels of fasting C-peptide islet cell antibodies are associated with this immunoregulatory abnormality.
ACTH control of steroid secretion from adrenal cells of the developing Rhesus monkey (Macaca mulatta)
Authors: Roebuck Margaret M. , Jones Colin T. , Robinson Jeffrey S. , Mitchell Murray D. , Thorburn Geoffrey D.
Published: December 2008

Abstract. Cells from adrenal glands of 140–160 days foetal, neonatal and infant Rhesus monkeys (Macaca mulatta) were prepared, by collagenase digestion and incubated with 10 pg– 16 ng/ml ACTH. The production of cortisol, androstenedione, corticosterone, progesterone and prostaglandins was measured. The cortisol production in the 140 day and 160 day foetuses and in the neonatal adrenal cells was comparable. It was 2-fold higher in adrenal cells of 6 month infant monkeys. In all the groups there was an increasing production of cortisol with increasing ACTH concentration, and a response to low physiological concentrations of ACTH.

The androstenedione production was significantly greater in the 160 day foetuses than in either those of 140 days or of the neonate which demonstrated a poor response to increasing ACTH concentrations. It responded well to increasing ACTH in adrenal cells from 6 month infant monkeys. Corticosterone output was 1/10th of cortisol with only the 140 day foetuses showing an increase in production with increasing ACTH concentrations.

The results demonstrate that cells of the primate foetal adrenal gland are not inherently unresponsive to ACTH stimulation as regards cortisol production, which per/μg DNA does not appear to change over the last 25 days before term.
Evidence of altered dopaminergic modulation of Prl, LH and TSH secretion in patients with normoprolactinaemic amenorrhoea
Authors: Hagen Claus , Petersen Karsten , Djursing Henning , Andersen Anders Nyboe
Published: December 2008

Abstract. Basal plasma concentrations of Prl, LH, FSH, GH, TSH, T3, T4, resin T3 uptake (RT3U), and oestradiol as well as hormone responses to iv metoclopramide (MTC) were investigated in 16 consecutive patients with normoprolactinaemic, normogonadotrophic amenorrhoea. The control group consisted of 17 normal menstruating women between day 3 and 6 of the menstrual cycle. The mean age of the amenorrhoeic patients was 24.0 years (range 19 to 34) and the mean duration of amenorrhoea was 31 months (range 12 to 60).

Amenorrhoeic patients had significantly (P < 0.05) lower basal levels of LH, oestradiol and RT3U, whereas other hormone levels were similar in the two groups. Plasma Prl and TSH concentrations rose significantly (P < 0.05) after the administration of MTC in the two groups. A significant positive correlation (r = 0.69 P < 0.01) was found between the TSH response to MTC and basal TSH levels in controls, but not in amenorrhoeic patients. Plasma LH levels increased significantly (P < 0.05) in amenorrhoeic patients, but not in controls. The Prl and TSH responses to MTC were significantly (P < 0.001) lower in amenorrhoeic patients than in normal women. In amenorrhoeic patients none of the hormonal parameters correlated significantly (P > 0.05) with the percentage of ideal body weight. It is concluded that the hormonal changes in amenorrhoeic patients may in part be caused by a raised dopaminergic acvitity leading to a depression of central ovulatory mechanisms.
ACTH and β-endorphin secretion by three corticotrophic adenomas in culture. Effects of culture time, dexamethasone, vasopressin and synthetic corticotrophin releasing factor
Authors: Oosterom R. , Verleun T. , Uitterlinden P. , Hackeng W. H. L. , Burbach J. P. H. , Wiegant V. M. , Lamberts S. W. J.
Published: December 2008

Abstract. Dispersed corticotrophic cells of 3 patients with Nelson's syndrome were studied in tissue culture for up to 25 days. During this culture period a parallel decrease with time was seen in ACTH and β-endorphin-like immunoreactivity (LIR) release. A concomitant decline was observed for intracellular hormones. The time course of hormone release showed a parallel secretion of ACTH and β-endorphin-LIR up to 8 h.

Both the release of ACTH and β-endorphin LIR were stimulated by 0.1 μm lysine vasopressin (LVP) in all three adenoma cell cultures. Dexamethasone (0.1 and 1 μm) suppressed basal hormone secretion for 4 h. Synthetic ovine corticotrophin-releasing factor (CRF) at 10 and 100 nm stimulated the secretion of ACTH and β-endorphin LIR maximally. This stimulation was higher than observed with maximal stimulative concentration of LVP (0.3 μm). The CRF-mediated hormone secretion was calcium-dependent. Dexamethasone (0.1 μm) blocked the stimulating effect of 10 nm CRF completely.

Gel-filtration chromatography demonstrated the cells to secrete both β-lipotrophin (β-LPH) and β-endorphin. The ratio of β-LPH to β-endorphin released remained constant upon stimulation by LVP and CRF. HPLC studies demonstrate the possibility that several β-endorphin fragments, including α-endorphin and γ-endorphin, were secreted by cells from a Nelson tumour. CRF caused a simultaneous parallel stimulation of the release of these peptides.
Highly specific antisera against native ovine follitropin (oFSH) obtained from crude antisera by affinity chromatography on solid-phase undissociable lutropin (LH) column
Authors: Poirier J. C. , Combarnous Y. , Blanc M. R.
Published: December 2008

Abstract. Antibodies recognizing determinants of the α-subunit, which is common to all glycoprotein hormones, were eliminated from antisera against native oFSH by affinity chromatography. Since the free α-subunit is immunologically different from the α-subunit in the intact hormone, we did not use an α-subunit affinity column. Instead, the antisera were applied to an LH affinity column. However, because intact LH dissociates in the conditions used to elute the purified antibodies, we prepared an LH derivative with covalently-linked subunits and coupled it to gel matrix. By this method oFSH antisera were freed from their non-specific antibodies. The cross-reaction of ovine lutropin in the oFSH radioimmunoassay (RIA) was lowered from 2% to less than 0.1%. Moreover, as the columns can be used repeatedly over long periods with no apparent loss of efficiency, large volumes of antiserum can be treated in this manner.
The biological assay of human somatomedin A: improvement by small molecular weight natural molecules
Authors: Heulin Marie-Hélène , Artur Michèle , Geschier Colette , Straczek Jean , Vescovi Guy , Belleville Francine , Paysant Pierre , Nabet Pierre
Published: December 2008

Abstract. Somatomedin activity is often measured by 35SO4 uptake in pelvic chick embryo cartilage. This assay gives good results when the somatomedin activity is measured in serum, but often gives uninterpretable results for purified somatomedin.

An ultrafiltrate (UF 1000) obtained from human normal serum, added to the incubation medium allows measurement of biological somatomedin activity even when somatomedin is highly purified. UF 1000 contains some compounds of molecular weight lower than 1000 daltons. UF 1000 acts either when used simultaneously with somatomedin or in pre-incubation with cartilage before testing biological activity. So, we chose to use it in pre-incubation (1 h) at the optimal concentration of 10% (v/v), the standard curves being realized with normal serum retentates. In these conditions, the proper action of UF 1000 does not interfere with calculation of somatomedin activity.

This method has enabled us to show that a diminution of serum somatomedin activity can be linked either to an anomaly of UF 1000 or to a somatomedin deficiency.
The hypothalamic-pituitary-thyroid axis in Type 1 diabetes: influence of diabetic metabolic control
Authors: MacFarlane I. A. , Sheppard M. C. , Black E. G. , Gilbey S. , Wright A. D.
Published: December 2008

Abstract. The influence of diabetic metabolic control on indices of thyroid function was studied in 9 euthyroid, insulin-dependent (Type 1) diabetics. During chronic poor metabolic control (mean fasting blood glucose 13 mmol/l and HbA1 concentrations 14.7%) serum T3 concentrations were low (P < 0.01) while serum T4 and basal TSH concentrations were normal. After 6–8 weeks of improved metabolic control, mean HbA1 concentrations had fallen to 10.7% (P < 0.01) and serum T3 concentrations had increased into the normal range. Serum T4 and basal TSH concentrations were unchanged. The serum TSH response to iv TRH remained normal throughout the study. In Type I diabetics, with chronic poor metabolic control, the serum T4 concentration and the TSH response to TRH are therefore appropriate indicators of thyroid function.
Developmental pattern of TRH-degrading activity and TRH content in rat pancreas
Authors: Aratan-Spire Sonia , Wolf Bryan , Czernichow Paul
Published: December 2008

Abstract. Thyrotrophin-releasing hormone (TRH), like several other neuropeptides, has been detected in the gastro-intestinal tract of adult rats. More recently, elevated concentrations of TRH have been found in the neonatal rat pancreas. This study was undertaken to evaluate pancreatic TRH degrading activity (TRH-DA) in infant rats from birth until adult life. Pancreatic TRH of age-matched rats was also measured by radioimmunoassay.

TRH-DA was present in normal adult rat pancreas; though absent at birth and in the early postnatal period up to day 7, this activity was detected during the remainder of the developmental period. TRH content (pg ± sem per pancreas) was 1139 ± 88 on day 1, reached a peak value of 7360 ± 758 at day 2 and then decreased steadily to adult level.

TRH-DA has been found to be present at birth in hypothalamus and liver but not in plasma. The developmental patterns of TRH-DA in plasma and in pancreas were parallel and seem to be thyroid hormone dependent. The absence of TRH-DA in the neonatal pancreas may also be related to the high TRH concentrations detected in this organ during the neonatal period.
Gastro-intestinal polypeptides in patients treated for medullary carcinoma of the thyroid
Authors: Rasmusson Bente
Published: December 2008

Abstract. In 12 patients treated 2 to 58 months previously for medullary carcinoma of the thyroid, basal serum concentrations of calcitonin, gastrin, vasoactive intestinal polypeptide, glucagon, insulin, and pancreatic polypeptide were measured in search of any correlation between these and the clinical course of the disease.

All patients had elevated serum calcitonin levels indicating present disease. One patient had increased serum concentrations of several hormones. Another had achlorhydria and high serum gastrin levels. No relationship between calcitonin and gastro-intestinal polypeptides was found in 11 patients. No correlations were found between serum levels of polypeptides and the occurrence of diarrhoea in 5 patients.

It is concluded that gastro-intestinal polypeptides, which are produced by other apudomas, are not secreted in more than normal concentrations under basal conditions, by the majority of patients previously treated for medullary carcinoma of the thyroid.
FSH, LH and prolactin levels, ovarian follicular development and ovarian responsiveness to FSH in the Snell dwarf mouse
Authors: de Reviers M. M. , Viguier-Martinez M. C. , Mariana J. C.
Published: December 2008

Abstract. The homozygous Snell dwarf mouse is sterile. It has been shown that pituitary hormone levels are low in 3 month old animals except for FSH and LH whose pituitary contents and plasma concentrations are normal. In this study, the pituitary FSH, LH and prolactin (Prl) content, the FSH plasma concentration and the ovarian follicular development of the Snell dwarf mouse were studied at 18, 20, 24, 40 and 80 days of age. Normal mice were also studied at the same age and served as controls. Pituitary FSH was significantly lower in dwarf mice compared with controls during the period days 18 to 30, while plasma FSH was significantly lower during the period days 20 to 80. Pituitary LH was significantly lower in dwarf mice during the period days 18 to 40. In normal mice, pituitary Prl increased with age, but remained consistently low in dwarf mice.

The normal number of growing follicles was similar in dwarf mice and controls up to day 30, but thereafter the total number of growing follicles was greater in the controls. In the dwarf mice, the production of antral follicles was low and there were no ovulations. The rates of atresia were similar in the two genotypes. The responsiveness of the dwarf mouse ovary to FSH was then examined. When dwarf and control mice were supplemented with FSH for 5 days starting at 24 days of age, the ovarian and uterine weights increase 6- and 5-fold, respectively, in the dwarf mice, and 2- to 3-fold in the normal mice. When dwarf mice were supplemented with FSH for 4 days starting at 30 to 40 days of age, there was an increase in the total number of growing follicles, a greater number of the more mature classes and a lower rate of atresia compared with untreated dwarf mice.

Low FSH levels during the prepubertal period are probably not the sole cause of dwarf mouse sterility. We believe that the dwarf mouse is a good animal model for the study of the role of pituitary hormones in ovarian follicular development.
Regulatory influence of relaxin on human cervical and uterine connective tissue
Authors: Wiqvist Ingrid , Norström Anders , O'Byrne Elizabeth , Wiqvist Nils
Published: December 2008

Abstract. Cervical tissue was obtained from women undergoing legal abortion in the 7th–15th week of gestation and tissue from the lower uterine segment was excised at elective Casearean section in the 38th–40th week. The specimens were incubated with [3H]proline in the presence of relaxin or prostaglandin E2 (PGE2).

Relaxin had a concentration related inhibitory effect on the radiolabelling in the 7th–9th week but failed to influence the amino acid uptake in the 10th–15th week of pregnancy. PGE2 had the inverse effect, i.e. no influence in the former group but reduced incorporation of proline in the latter group of patients. Incubation of tissue from the lower uterine segment showed a similar response as that of the early pregnant cervix. It is concluded that relaxin has a significant influence on [3H]proline incorporation by cervical and uterine tissue under in vitro experimental conditions.
The effect of testosterone on ram spermatozoa collective motility treated by antimycin A
Authors: Ailenberg M. , Bartoov B. , Mayevsky A.
Published: December 2008

Abstract. The effect of testosterone on collective motility of antimycin A-treated, Ficoll-400-washed ejaculated ram spermatozoa was studied. The lowest concentration of antimycin A which blocked collective motility in hexose deprived cells (0.4 × 109 cells/ml) was 2 × 10−7 m. Fructose, glucose and mannose, but not galactose, sorbitol or inositol, served as energy sources for collective motility. Cortisol, 5-β-DHT, androsterone and 5-α-pregnan 3-β-01-20-one did not affect collective motility. Testosterone inhibited collective motility in a dose-dependent fashion. However, it did not affect lactic acid accumulation. The effect of testosterone was noted both on cells suspended in buffer containing fructose and on exogenously starved cells treated with fructose after collective motility arrest. It was concluded that testosterone might exert its inhibitory effect on motility by uncoupling fructolytic energy production to the tail motility system.
Induction of murine α-foetoprotein synthesis by oestradiol
Authors: Hau J. , Chemnitz J. , Teisner B. , Tornehave D. , Svendsen P.
Published: December 2008

Abstract. The synthesis of murine α-foetoprotein (m-AFP) was induced in 43 out of 47 adult mice of both sexes by sc administration of 100 μg oestradiol-17β every second day. The m-AFP serum levels of the oestrogen treated male and female mice were 7 and 17%, respectively, of the levels in mice during late pregnancy. Immunohistochemical examination of liver tissue revealed the intracellular presence of m-AFP in less than 0.5% of the hepatocytes scattered throughout the liver of the oestrogen treated mice.
Comparison of growth and somatomedin C responses following growth hormone treatment in children with small-for-date short stature, significant idiopathic short stature and hypopituitarism
Authors: Grunt J. A. , Howard C. P. , Daughaday W. H.
Published: December 2008

Abstract. Somatomedin-C (Sm-C) and growth hormone (GH) levels were determined before, during and after human growth hormone (hGH) treatment in 18 children with small-for-date short stature (SDSS), 7 children with significant idiopathic short stature (SISS) and 14 children with hypopituitarism. Data on the acute effects of hGH on Sm-C were compared to growth responses after 6 to 9 months therapy. Eleven of the 25 non-hypopituitary patients with normal basal and stimulated serum GH levels and normal basal Sm-C levels increased their rates of growth more than 3.0 cm/year. This compared with 11 of the 14 children with hypopituitarism who increased their rates of growth by at least 3.0 cm/year when treated with GH. Neither the basal somatomedin levels nor the GH-stimulated somatomedin levels correlated well with subsequent growth in the non-hypopituitary patients. These studies indicate that GH therapy may be effective in treating short stature in children without demonstrable GH deficiency.
Effects of in vivo triiodothyronine and long acting thyroid stimulator (LATS) administration on the in vitro thyroid cAMP response to thyrotrophin and LATS
Authors: Ikeda Hitoshi , Chiu Shoo Cheng , Kuzuya Nobuaki , Uchimura Hidemasa , Nagataki Shigenobu
Published: December 2008

Abstract. The present study was undertaken to examine the effects of prolonged in vivo treatment with T3 and long acting thyroid stimulator (LATS) on in vitro responsiveness of mouse thyroid cyclic AMP to thyrotrophin (TSH) and LATS-immunoglobulin G (IgG). In control mice, thyroid cAMP concentrations after incubation with normal-IgG (10 mg/ml) for 2 h. TSH (10 mU/ml) for 10 min and LATS-IgG (10 mg/ml) for 2 h were 1.25 ± 0.11 (mean ± se) (n = 5), 15.87 ± 3.47 (n = 6) and 2.17 ± 0.25 pmoles/mg wet weight (n = 6), respectively. In mice given T3 (5 μg/ml in drinking water for 5 days, thyroid cAMP concentrations after an incubation with TSH were reduced by 50%, as compared to those of the control mice. They were also decreased in mice injected ip with 5 mg of LATS-IgG (1000%/5 mg in the McKenzie bioassay) daily for 5 days. Combined treatment with T3 and LATS decreased the cAMP response to TSH only to the same extent as did T3 alone, indicating that the inhibitory effects of T3 and LATS were not additive. Similar findings were observed with the thyroid cAMP response to LATS-IgG in vitro; either T3 or LATS treatment in vivo decreased cAMP response to LATS-IgG in vitro, but combined treatment with T3 and LATS did not cause further inhibition as compared with T3 or LATS treatment alone.

These results indicate, 1) that prolonged in vivo T3 treatment inhibits the in vitro thyroid cAMP response not only to TSH but also to LATS-IgG, 2) that prolonged in vivo LATS treatment also suppresses the thyroid cAMP response both to TSH and LATS-IgG and 3) that the inhibitory effects of LATS may not be due to the effects of LATS per se but to increases in circulating thyroid hormone levels induced by prolonged LATS treatment.
The prevalence and progression of autoimmune thyroid disease in the elderly
Authors: Lazarus J. H. , Burr M. L. , McGregor A. M. , Weetman A. P. , Ludgate M. , Woodhead J. S. , Hall R.
Published: December 2008

Abstract. Thyroid antibodies were measured by an enzyme-linked assay system (ELISA) on a random sample of 414 asymptomatic elderly people aged 70 years or more in a South Wales town in 1977. The prevalence of elevated titres of microsomal antibodies was 15.4% and of thyroglobulin antibodies 13.3%; 8.5% had an elevation of both antibodies. Five years later thyroid function was evaluated in 51(66.6%) of those people with raised antibody titres in 1977 and compared with a control group of 46 old people drawn from the original population.

Significant fluctuations of microsomal and thyroglubulin antibody titres were observed in two thirds of the antibody positive group. Three people in the control group developed positive thyroid antibodies during this period. Only 1 person in the antibody positive group became hypothyroid.

The prognostic significance of raised thyroid antibodies with or without elevated TSH levels is less in the elderly than in middle aged or younger people. The significance of the fluctuating antibody levels as measured by a more sensitive method remains to be determined.
Sex related goitrogenic effect of lithium carbonate in healthy young subjects
Authors: Perrild Hans , Hegedüs Laszlo , Arnung Klaus
Published: December 2008

Abstract. Eight healthy males and 8 healthy females without a family history of thyroid disease or detectable thyroid autoantibodies were given 300 mg of lithium carbonate twice a day for 28 days. Using a precise and accurate ultrasonic technique we demonstrated an increase in median thyroid volume from 18 ml on day 0 to 34 ml on day 28 (P < 0.005) in the female group, whereas the median thyroid volume was unchanged in the male group. A significant increase in basal serum TSH level and serum TSH levels 20, 60 and 90 min after 200 μg of TRH iv was found in both groups after 28 days of lithium treatment. The means of the individual TSH increments during the TRH test were not significantly different between the two sexes neither before nor after lithium treatment. After 14 and 28 days a significant fall in serum T4 levels was found in both sexes. 131I uptake (24 h) in the thyroid gland was increased in both sexes, but only in the male group was the mean PB131I (24 h) significantly reduced after 28 days of lithium treatment. In conclusion the present study suggests a difference in susceptibility of the thyroid gland to the growth stimulating effect of minute increments in serum TSH in young healthy males and females given lithium carbonate.
Immunoreactive parathyroid hormone, calcium, and magnesium in human cerebrospinal fluid
Authors: Balabanov S. , Töllner U. , Richter H.-P. , Pohlandt F. , Gaedicke G. , Teller W. M.
Published: December 2008

Abstract. Parathyroid hormone (PTH) was measured radioimmunologically in simultaneous plasma and cerebrospinal fluid (CSF) samples obtained from 72 patients aged 20 to 80 years without endocrine or psychiatric diseases and from 2 patients aged 40 and 70 years with secondary hyperparathyroidism due to renal insufficiency. They underwent routine diagnostic lumbar puncture because of suspected prolapse of a disc. Total calcium (Ca) and magnesium (Mg) were also determined in these samples by complexometry.

The following findings were obtained (ng/ml, median, range in brackets): Plasma PTH 1.7(0.7–6.6); CSF PTH 0.8 (0.5–2.3), respectively. No correlation was found between PTH concentrations in plasma and CSF in all 74 samples. The Ca concentrations in plasma, with a median of 2.3 mmol/l (2.1–2.6) were significantly higher than the Ca concentrations in CSF (median 1.1 mmol/l, range 0.4–1.3). The correlation between PTH and calcium levels in CSF was only weak (r = 0.284 P < 0.05). The Mg levels in CSF (median 1.1 mmol/l, range 0.7–1.6) were higher than Mg concentrations in plasma (median 0.9 mmol/l, range 0.6–1.1). No correlation was found between PTH and Mg in CSF. Our study demonstrated that in man PTH is a normal constituent of CSF.