bluuebunny/crossref_metadata_2025 huggingface dataset:
TSH-dependent production of T4 and T3 by metastases of a thyroid carcinoma
Authors: Ottevanger Petronella B , Hermus ARMM , Smals Anthony GH , Kloppenborg Peter WC
Published: June 2009

A patient with T4 and T3 production by metastases of a follicular thyroid carcinoma leading to TSH suppression is described. During a period of three years, plasma T4, T3 and TSH levels were measured in the substitution-free periods before the successive iodine-131 retention measurements and iodine-131 therapies, when the patient was at least two weeks without thyroid hormones. From the presented data it can be derived that the production of thyroid hormones by metastases was enhanced by endogenous TSH.
Increased hypothalamic somatostatin mRNA following dexamethasone administration in rats
Authors: Nakagawa Koji , Ishizuka Tatsuya , Shimizu Chikara , Ito Yoshito , Wakabayashi Ichiji
Published: June 2009

There is increasing evidence to suggest that supraphysiological doses of glucocorticoids suppress growth hormone secretion in vivo by augmenting somatostatin release from the hypothalamus; previously, we reported an increase in hypothalamic somatostatin content in dexamethasone-treated rats. To further examine whether the production of somatostatin really is augmented, hypothalamic somatostatin mRNA levels were determined by the Northern blot technique in female rats receiving 330 μg of dexamethasone daily for three days. In two series of experiments, hypothalamic somatostatin mRNA levels in dexamethasone-treated rats were significantly (p<0.05) increased to 133±19 (mean±sd)% and 153±38% of the controls. In the dexamethasone-treated rats, plasma growth hormone levels were markedly suppressed compared with those of the controls. These results further support the hypothesis that pharmacological doses of glucocorticoids increase the production and release of somatostatin from the hypothalamus and thus inhibit growth hormone secretion, overriding the direct stimulatory effect of glucocorticoids on growth hormone production at the pituitary level.
Iodide and T4 kinetics in plasma, thyroid gland and skin of 10-day-old rats: effects of iodine deficiency
Authors: Zeghal Najiba , Gondran François , Redjem Mebarka , Giudicelli Marie-Dominique , Aissouni Youssef , Vigouroux Emile
Published: June 2009

The effects of iodine deficiency on the peripheral metabolism of thyroid hormone in immature rat were evaluated by measuring the kinetics of iodide and thyroxine (T4) in control and iodine-deficient 10-day-old rats. Iodine-deficient pups were obtained by giving the mother drinking water containing perchlorate; this anion is not transferred but prevents iodine transfer in the mother's milk. Labelled iodocompounds were measured in plasma, thyroid and skin for 48 h following intravenous injection of Na131I plus [125I]T4. Data were interpreted by compartmental analysis. The iodide plasma clearance rate, plasma equivalent distribution volume, plasma concentration, production and iodine thyroid content of iodine-deficient rats were significantly lower (−29%, −31%, −84%, −89% and −87% respectively) than in control 10-day-old rats. The iodide thyroid uptake was reduced (−47%) but remained higher than the release of iodine as T4. Cutaneous iodine was lost much more quickly by iodine-deficient pups than by control pups, explaining the decreased iodide distribution volume. The parameters of T4 metabolism were not changed by iodine deficiency, except for a slight but significant reduction of the thyroxinemia and T4 pools (−13%). Thence, T4 production was not significantly changed (about 8 pmol/h in control and iodine-deficient rats). The labelled T4 curves in iodine-deficient and control skin were superimposed and the patterns of labelled T3 derived from [125I]T4 were identical. Thus, the skin of immature rats converts T4 to T3; this process was not disturbed by iodine deficiency. The thyroid function of immature rats is particularly resistant to iodine deficiency, but the mechanisms remain unknown.
Plasma vasopressin responses in postpartum hypopituitarism: impaired response to osmotic stimuli
Authors: Arnaout MA , Ajlouni K
Published: June 2009

The neurohypophyseal function was assessed in a group of 15 patients with postpartum hypopituitarism by measuring plasma arginine-vasopressin concentrations during 5% hypertonic saline infusion. None of the patients had symptoms of diabetes insipidus and all patients were on adequate cortisone and thyroxine replacement therapy before testing. The mean basal plasma vasopressin value in the patients (0.6±0.1 pmol/1) was significantly lower than that in the normal subjects (2.9±0.3 pmol/l; p<0.01), whereas the mean serum sodium, plasma osmolality, plasma renin activity and serum aldosterone values were similar in the two groups. During the osmolar load (5% hypertonic saline), the patients revealed varying degrees of arginine-vasopressin responses to the increase in plasma osmolality. Three patients showed normal arginine-vasopressin responses, 10 had subnormal responses, and 2 had no response. During the dehydration test, the patients revealed significantly lower maximum urine osmolalities (p<0.0025) with significantly higher concurrent mean plasma osmolality (p<0.0025) than the controls. None of the patients showed overt polyuria at the time of the study. The results indicate the impaired osmoregulation of arginine-vasopressin secretion to an osmolar stimuli in patients with postpartum hypopituitarism, suggesting neurohypophyseal damage. In patients with Sheehan's syndrome, partial diabetes insipidus seems to be much more frequent than previously believed.
Defective stimulation of proliferation and collagen biosynthesis of human bone cells by serum from diabetic patients
Authors: Brenner Rolf E , Riemenschneider Bert , Blum Werner , Mörike Martin , Teller Walter M , Pirsig Wolfgang , Heinze Eberhard
Published: June 2009

We studied the influence of fasting serum from nine insulin-dependent diabetic children and adolescents under insufficient metabolic control on normal human bone cells in vitro compared with serum from eight sex- and age-matched controls. Cell number 24 h after plating was significantly less under diabetic serum, indicating impaired cell attachment, spreading and initiation of cell proliferation. Cell number after five days was reduced by 1% diabetic serum, while higher serum concentrations had diverging effects on osteoblast proliferation. Collagen synthesis of human osteoblasts was significantly reduced by 8% diabetic serum compared to 8% control serum, while synthesis of non-collagenous proteins was not affected. Duration of diabetes (several weeks up to 12 years) had no influence on these parameters. The serum from one patient, which was studied a second time under excellent metabolic control three months later, however, had lost its inhibitory influence on collagen synthesis of osteoblasts. The pattern of the interstitial collagen types I, III and V was not altered by diabetic serum. These results indicate that defective regulation of proliferation and collagen synthesis of osteoblasts by components present in human diabetic serum may be an important factor in the development of diabetic osteopenia. The negative influence might be explained in part by reduced levels of IGF-I and elevated levels of IGF binding protein-1 in the diabetic sera.
Examination of antithyroid effects of smoking products in cultured thyroid follicles: only thiocyanate is a potent antithyroid agent
Authors: Fukayama Haruhisa , Nasu Michiyo , Murakami Saburo , Sugawara Masahiro
Published: June 2009

We studied the antithyroid action of cigarette smoking products (nicotine, cotinine, and thiocyanate) in the physiological culture system of porcine thyroid follicles. Iodide uptake, iodine organification, de novo thyroid hormone formation, and iodide efflux were measured in the presence of 0–200 μmol/l nicotine, cotinine, or potassium thiocyanate. Nicotine and cotinine did not inhibit iodide transport or thyroid hormone formation. Thiocyanate concentrations equivalent to serum levels of smokers showed three independent antithyroid actions: (i) inhibition of iodide transport, (ii) inhibition of iodine organification, and (iii) increased iodide efflux. Inhibition of iodide transport by thiocyanate was competitive with iodide and independent of TSH concentration. Thiocyanate did not inhibit TSH mediated cAMP production or Na+K+ATPase activity, a sodium pump for iodide transport. When 50 μmol/l thiocyanate was added 2 h after incubation with iodide or when 1 μmol/l thiocyanate was added from the beginning of incubation, iodine organification was inhibited without changing iodide transport. De novo thyroid hormone formation was clearly inhibited by 50 μmol/l thiocyanate. Thiocyanate increased iodide efflux although the degrees of iodide efflux by 10 μmol/l and 100 μmol/l thiocyanate did not differ significantly. In summary, thiocyanate, a product of smoking, has three independent antithyroid activities. The data of iodide transport kinetics suggest that thiocyanate can be an antithyroid agent particularly in iodine deficiency.
Cytological maturity of zona fasciculata cells in the fetal sheep adrenal following ACTH infusion: an electron microscope study
Authors: Perry Roslyn A , Tangalakis Kathy , Wintour E Marelyn
Published: June 2009

Electron microscopy was used to assess the cytological maturity of the zona fasciculata cells in the adrenal cortex of fetal sheep at 105 days of gestation, following several ACTH infusion regimes. The aim of this study was to correlate the morphological appearance of the fetal adrenal zona fasciculata cells with the expression of the steroid hydroxylase genes and the fetal plasma cortisol concentrations in a parallel study. Immediately following infusion of ACTH for 24 or 72 h, the zona fasciculata cells at the cortico-medullary junction were more mature than those in the saline-infused controls. When ACTH infusions were withdrawn for 24–72 h prior to the termination of the experiment, the deep cortical cells appeared less mature than those in fetuses which had received ACTH right up until the time of tissue collection. Following ACTH administration, mitochondrial changes preceded changes in the smooth endoplasmic reticulum, and when ACTH was withdrawn, the smooth endoplasmic reticulum responded before the mitochondria. The study demonstrated a correlation between the cytological maturity of the deep zona fasciculata cells and the expression of the genes for the steroidogenic enzymes P-45017α and P-450scc in the 105-day fetal sheep adrenal following ACTH infusion.
Studies on regulation of insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-4 production in human bone cells
Authors: Mohan Subburaman , Strong Donna D , Lempert Uta G , Tremollieres Florence , Wergedal Jon E , Baylink David J
Published: June 2009

Previous studies have shown that the actions of IGF-II in bone are determined not only by its concentration, but also by the concentration of IGFBP-4 as well as other IGFBPs. In this study, we sought to determine by Western ligand blotting the effects of growth hormone, IGF-I and IGF-II on the production of IGFBP-3 and IGFBP-4 in TE89 human osteosarcoma cells and in untransformed normal human bone cells derived from rib. Human growth hormone at 10 μg/l decreased the amount of IGFBP-4 but had no effect on the IGFBP-3 level in the conditioned medium of low density cultures of TE89 cells and human bone cells derived from rib. Human growth hormone had no effect on IGFBP-3 or IGFBP-4 levels in the conditioned medium of high density human bone cell cultures. IGF-I and IGF-II, which increased human bone cell proliferation, decreased the level of IGFBP-4 (30% of control at 100 μg/l IGF-I and IGF-II) but increased the level of IGFBP-3 (3–10 fold at 100 μg/l IGF-I and IGF-II) after 48 h of treatment in the conditioned medium of both low and high density TE89 cell cultures. Similar changes in IGFBP-3 and IGFBP-4 levels were also seen in the conditioned medium of human bone cells derived from rib after treatment with IGF-I and IGF-II. Studies to determine the underlying molecular mechanisms by which IGF-II decreased the amount of IGFBP-4 in the conditioned medium revealed that IGF-II decreased the IGFBP-4 mRNA abundance and increased the IGFBP-3 mRNA abundance in human bone cells. Based on the above findings, we conclude that the production of both IGFBP-3 and IGFBP-4 is regulated in bone cells and that local and systemic agents may modulate the responsiveness of bone cells to IGFs by regulated secretion of IGFBP-3 and IGFBP-4.
Hormonal responses to the new potent GnRH antagonist Cetrorelix
Authors: Klingmüller D , Schepke M , Enzweiler C , Bidlingmaier F
Published: June 2009

GnRH antagonists, unlike the GnRH agonists, immediately suppress gonadotropins and testosterone secretion without initial stimulatory effect. We report here on a single-dose study with the new GnRH antagonist Cetrorelix (Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal3, D-Cit6, D-Alal0) in 25 normal men. The study involved five different dose groups (0.25, 0.5, 1.0, 1.5 or 3.0 mg) and subjects were observed over a 40 h period. Five men served as controls. Serum levels of LH, FSH and testosterone decreased rapidly with a dose-related decline for testosterone of 25%, 24%, 41% 53% and 72%, respectively, for testosterone within the first 8 h of antagonist administration. All effects were reversible and no serious side effects were observed. Thus, this GnRH antagonist is active in men even in small doses and could become a new therapeutic tool for sex hormone-dependent diseases. Cetrorelix seems to have the highest suppressive rate per mg peptide of all other antagonists from the literature, such as Nal-Glu (Ac-D-Nal(2)1, D-Phe(4Cl)2, D-Pal3, Arg5, D-Glu6(AA), D-Alal0), Detirelix (Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Alal0) or 4F (Ac-Δ 3Prol, 4F-D-Phe2, D-Trp3,6). During the time of suppression after a dose of 3 mg there was an LH and testosterone peak in the early morning coinciding with the testosterone peak in untreated men. The GnRH antagonist seems to unmask the circadian rhythm of LH secretion.
Thymostimulin effects on lymphoid organs in Ames dwarf mice
Authors: Villanua Maria A , Szary Agnieszka , Esquifino Ana I , Bartke Andrzej
Published: June 2009

This work was undertaken to study the effects of thymostimulin (TP-1) on the immune function in Ames dwarf mice, and to relate these effects to PRL and/or GH deficiency in these animals. Male Ames dwarf mice implanted with pituitaries from normal mice under the kidney capsule, sham-operated dwarf mice and normal immature or adult mice were injected daily for five days with TP-1. In comparison to normal animals, sham-operated dwarf mice had markedly lower body, thymus and spleen weights, as well as a lower number of lymphocytes in the spleen and in the thymus and the natural killer (NK) activity of spleen lymphocytes. Ectopic pituitary transplants produced the expected enhancement of body weight gain and increased spleen and thymus weights, which reached the values found in normal (non-dwarf) animals. The numbers of lymphocytes in the spleen and thymus were significantly increased in pituitary-grafted dwarf mice, but the grafts did not modify the cytotoxic activity of NK spleen cells, or the number of peripheral white blood cells (PWBC). In sham-operated dwarf mice, TP-1 treatment did not modify the number of cells in the spleen and thymus, or the NK activity. In pituitary-grafted dwarf mice, treatment with TP-1 induced an increase in the number of spleen lymphocytes and in the NK activity of spleen cells without affecting the weight of lymphoid organs or the number of thymic cells. Plasma prolactin (PRL) and growth hormone (GH) levels of pituitary-grafted dwarf mice were not changed after TP-1 administration. Surprisingly, the NK activity of spleen lymphocytes in normal adult mice was greatly increased after TP-1 administration. These findings suggest that the thymic extract TP-1 can exert a major stimulatory influence on NK activity of spleen lymphocytes in adult mice, and potentiate some of the stimulatory effects of hormones secreted by ectopic pituitary transplants on the immune function of Ames dwarf mice. These effects are not mediated by modifications of the release of PRL or GH.
The "feto-maternal" thyroid function interrelationships in an iodine-deficient region in Africa—the role of T3 in possible fetal defence
Authors: Das SC , Isichei UP
Published: June 2009

The thyroid status was investigated in 26 pregnant African women at term delivery in an iodine-deficient region (Jengere) of Nigeria, West Africa including the measurement of serum T4, T3, TSH, thyroxine binding capacity, TBG, free thyroxine index (FT4I) and the results were matched with those obtained in a corresponding group of 46 women at delivery in Jos, the non-iodine-deficient region which was used as a control. Corresponding cord-blood samples were obtained from all the neonates of the two groups. Twenty-three urinary samples in the former and 14 in the latter group were analysed for iodide levels to ascertain the degree of iodine deficiency. The results demonstrate that compared to the values seen in the Jos group the maternal serum T4, T3 and FT4I levels were significantly reduced in the iodine-deficient group, while TSH, TBG and thyroxine binding capacity were elevated. Cord serum samples showed a corresponding fall in T4 and FT4I levels in the group from the iodine-deficient region, while the T3 levels were significantly elevated with a concurrent significant rise in TSH and TBG levels. Significant correlations were found between the maternal and cord serum T4, TSH, TBG, thyroxine binding capacity and FT4I levels, but not T3. From these findings we suggest that fetal T3 plays an important defensive role against the danger of long-standing environmental iodine deficiency.
Hypercortisolism with non-pigmented micronodular adrenal hyperplasia: transition from pituitary-dependent to adrenal-dependent Cushing's syndrome
Authors: Hocher Berthold , Bähr Volker , Dorfmüller Severin , Oelkers Wolfgang
Published: June 2009

We report on a female patient with Cushing's syndrome in whom we observed the transition from pituitary dependency to adrenal dependency. Basal ACTH and cortisol values, the CRH test, the dexamethasone suppression test as well as CT of the pituitary and the adrenal gland all reflected pituitary-dependent Cushing's disease in 1985. The patient refused treatment, but presented again five years later. At that time ACTH was suppressed before and after CRH injection. Plasma cortisol did not respond to CRH. After ketoconazole therapy, ACTH was within the high normal range. The patient underwent bilateral adrenalectomy. The adrenals exhibited a bilateral micronodular hyperplasia of the zona fasciculata. In vitro examination of adrenal cells revealed a maintained ACTH response. Some weeks postoperatively, the patient died from pneumonia. Histological examination later showed a chromophobe pituitary microadenoma; ACTH was demonstrated immunohistologically in the adenoma. We postulate that some cases of pituitary Cushing's disease initially exhibit a bilateral homogeneous adrenal hyperplasia which then develops into a nodular hyperplasia; in the next stage of the disease, single micronodules may become autonomous and elevated cortisol levels suppress ACTH secretion of the pituitary adenoma.
Long-term treatment of Laron type dwarfs with insulin-like growth factor-1 increases serum insulin-like growth factor-binding protein-3 in the absence of growth hormone activity
Authors: Kanety Hannah , Karasik Avraham , Klinger Beatrice , Silbergeld Aviva , Laron Zvi
Published: June 2009

Insulin-like growth factor binding protein-3 (IGFBP-3) is the major carrier of insulin-like growth factor I (IGF-1) in serum, and its production is growth hormone (GH) dependent. It is unclear whether in humans IGFBP-3 production is directly regulated by GH or mediated via IGF-I. We addressed this question in six patients with Laron-type dwarfism, a syndrome characterized by the absence of GH receptor activity (LTD), who were chronically treated with recombinant IGF-I. Analysis of the electrophoretic profiles of serum IGFBPs in these patients by Western ligand blotting revealed an extremely low IGFBP-3 level. A striking progressive increase in serum IGFBP-3 was observed with continuous treatment, despite the absence of GH action. In LTD children, serum IGFBP-3 increased up to 19-fold after six months of therapy and equalled levels observed in controls, whereas in adult LTD patients the increase was smaller. A rise in serum levels of 34, 30 and 24 kDa BPs (presumably IGFBP-2, -1 and -4, respectively was also noted with chronic IGF-I therapy. This proof of GH-independent induction of IGFBP-3 by IGF-1 may be a major advantage in the therapeutic use of biosynthetic IGF-I in several types of short stature children.
Plasma levels of several androgens and estrogens from birth to puberty in male domestic pigs
Authors: Schwarzenberger Franz , Toole Geoffrey S , Christie Heather L , Raeside James I
Published: June 2009

Plasma concentrations for several androgens and estrogens were determined in male domestic pigs from birth to eight months of age. Samples (N = 6) of blood were collected from Yorkshire males at weekly intervals from birth to four weeks, and thereafter at monthly intervals to eight months. Radioimmunoassays were done without extraction from plasma for dehydroepiandrosterone sulphate, androstenedione and estrone sulphate. Other steroids were measured after solid-phase extraction, separate elution of unconjugated and conjugated fractions, and solvolysis of sulpho-conjugated steroids (testosterone, 5α-androstane-3β, 1 7β-diol, epiandrosterone, 19-nortestosterone and estradiol-177β). All steroids showed a peak in plasma levels at 2–4 weeks after birth. Concentrations remained low from 2–5 months and rose markedly thereafter. Most steroids were present in much greater quantities as sulpho-conjugated compounds. Concentrations of testosterone sulphate and testosterone were similar (9.4 μmol/l) at three weeks but the sulphated form predominated after six months of age. This study shows that during postnatal development the testes of the domestic pig are remarkably active in steroidogenesis with a peak at 2–4 weeks after birth. Also, the range of steroid products seen at this stage is comparable to that shown by the mature boar.
Stimulation of mitogenesis in human thyroid epithelial cells by endothelin
Authors: Eguchi Katsumi , Kawakami Atsushi , Nakashima Munetoshi , Ida Hiroaki , Sakito Souko , Sakai Masahiro , Terada Kaoru , Kawabe Yojiro , Fukuda Takaaki , Ishikawa Naofumi , Ito Kunihiko , Nagataki Shigenobu
Published: June 2009

We investigated whether a potent vasoconstrictor, endothelin, stimulated the proliferation of human thyroid epithelial cells (thyrocytes). [3H]-thymidine incorporation into normal thyrocytes and thyrocytes from patients with Graves' disease was significantly increased at 10−9 mol/l endothelin. reaching a plateau at 10−8 mol/l. The proliferative responses of the thyrocytes obtained from patients with Graves' disease were similar to those of normal thyrocytes. Furthermore, the cell number of thyrocytes stimulated by endothelin was increased as compared with that of unstimulated thyrocytes. Neither indomethacin nor heparin affected this endothelin-stimulated thyrocyte proliferation. When thyrocytes were cultured with both endothelin and recombinant interleukin 1β, there was an additive effect on thyrocyte proliferation. The Ca2+ entry blocker, verapamil, inhibited both the proliferative responses of thyrocytes to endothelin and the additive effect of endothelin and recombinant interleukin 1β on thyrocyte proliferation. These results suggest that endothelin functions as a growth-promoting factor for human thyrocytes, presumably through intracellular calcium influx.
Significance of steroidogenic enzymes in the pathogenesis of adrenal tumour
Authors: Shibata Hirotaka , Suzuki Hiromichi , Ogishima Tadashi , Ishimura Yuzuru , Saruta Takao
Published: June 2009

We examined both activities and amounts of steroidogenic cytochrome P-450s at the posttranslational protein level and steroid contents in the adrenocortical adenoma from patients with primary aldosteronism and Cushing's syndrome. Aldosterone synthase cytochrome P-450 (human P-450aldo) was detected in the tumour portion of aldosterone-producing adenoma, but not in the normal control adrenals, at the protein level. Neither the activities nor the amounts of other P-450s in the tumour portion of aldosterone-producing adenoma were significantly different from those in the non-tumour portion in the adenoma and the normal control adrenals. The aldosterone content was significantly elevated, while the androstenedione content was significantly decreased in the tumour portion of the adenoma compared with that in the normal control adrenals. In Cushing's syndrome, both the activities and amounts of P-45017α and P-450c21 were significantly elevated in the tumour portion compared with the non-tumour portion of the adenoma and the normal control adrenals, while those of P-450scc and P-45011β in the tumour portion were not significantly different from the normal control adrenals. The cortisol content was significantly elevated, while the amounts of aldosterone and 18-hydroxydeoxycorticosterone in the tumour portion of the adenoma were significantly decreased compared with those in the normal control adrenals. These results demonstrate that overexpression of P-450aldo in aldosterone-producing adenoma, and those of P-45017α and P-450c21 in cortisol-producing adenoma may play some role in the pathogenesis of primary aldosteronism and Cushing's syndrome, respectively.
Biological and immunological properties of the international standard for FSH 83/575: isoelectrofocusing profile and comparison with other FSH preparations
Authors: Simoni Manuela , Jockenhövel Friedrich , Nieschlag Eberhard
Published: June 2009

The new international standard for FSH, IS 83/575, has been analyzed, after isoelectric focusing separation, by Sertoli cell in vitro bioassay, radioligand receptor assay and two highly specific immunometric assays. Its molecular composition was then compared with the isoelectric focusing profiles obtained from the fractionation of the reference preparation 2nd IRP 78/549 and from pools of human male and female pituitary extracts and male and female sera. The results showed that >80% of immunoreactive and bioactive FSH in the IS 83/575 has a pI value <4, while such very acidic material was represented much less in the other FSH preparations tested. All the immunoreactive material contained in the IS 83/575 was shown to be capable of receptor binding and bioactivity in vitro. A generally good correspondence between IEF profiles obtained by bioassay and by immunofluorimetric assay was evident in the case of IS 83/575, 2nd IRP 78/549 and pituitary extracts, although the profiles recorded by immunofluorimetric assay were rather smooth and more isoforms were detected by bioassay. A striking discrepancy between immunoreactive FSH and bioactive FSH was observed after isoelectric focusing fractionation of the serum pools, in which some bioactive material was not detected by immunofluorimetric assay and some of the immunoreactive FSH peaks were devoid of bioactivity, indicating that serum contains inhibitors of FSH action and that immunometric assays based on monoclonal antibodies may miss some bioactive FSH isoforms. Taken together, these results suggest that the IS 83/575 is not fully representative of pituitary and serum FSH, and its use for calibration of modern immunometric methods based on monoclonal antibodies is unlikely to resolve current problems of inaccuracy in measurements of serum FSH.
Long-term treatment of macroprolactinomas with CV 205-502
Authors: Kvistborg Anette , Halse Johan , Bakke Soren , Bjøro Trine , Hansen Egill , Djøseland Ole , Brownell Judith , Jervell Jak
Published: June 2009

The long-term efficacy and tolerability of CV 205-502, a non-ergot dopamine agonist with D-2 receptor affinity, were studied for up to 36 months in 16 patients with macroprolactinomas. Prolactin values were reduced in all cases, becoming either normalized or suppressed in 12. The pituitary tumor size was reduced in the 13 patients with an obvious tumor and visual function normalized in all six patients with initial defects. Concomitantly we observed improvement in gonadal function, galactorrhea, headache, libido and general well-being. Adverse reactions were experienced by 1 5 patients during dosage increment and caused one patient to discontinue the medication. Seven patients had persistent adverse effects which prohibited a dosage increase of CV 205-502, sufficient to normalize PRL levels in three. Two patients experienced serious adverse events, causing the discontinuation of treatment in one case. In eight patients treatment with CV 205-502 and bromocriptine could be compared. Three patients responded better to CV 205-502 than to bromocriptine treatment. Only one patient preferred bromocriptine to CV 205-502 for long-term treatment. We conclude that CV 205-502 is an effective and in most cases well-tolerated treatment for patients with macroprolactinomas. CV 205-502 is preferable to bromocriptine as an initial treatment and should also be tried in patients where treatment with bromocriptine has failed.
Nalmefene enhances LH secretion in a proportion of oligo-amenorrheic athletes
Authors: McArthur Janet W , Turnbull Barry A , Pehrson Jon , Bauman Mary , Henley Karen , Turner Adrian , Evans William J , Bullen Beverly A , Skrinar Gary S
Published: June 2009

The influence upon LH secretion of doses of nalmefene, an orally effective congener of naloxone, and a placebo was compared in nine oligo-amenorrheic athletes with that in five regularly menstruating non-athletic women as a test for periodic elevations in hypothalamic opioid tone. After a 360-min control period, LH levels were followed for an additional 360 min following ingestion of the medications in random order approximately six weeks apart, 10-min blood sampling being employed throughout. The mean amplitude post-nalmefene in the athletes was significantly greater than pre- (p <0.05), although there were no differences in the frequency of LH pulses after placebo or nalmefene ingestion. Subjects were labelled as "responders" if their peak AUC after treatment exceeded their pretreatment AUC for LH by more than 1.96 sd (p<0.05). There were no placebo responders, but 5/9 of the athletes and 1/5 of the menstruating controls were classified as nalmefene responders (p<0.05). In addition, a variable proportion of the athletes (but none of the controls) experienced symptoms suggestive of narcotic withdrawal 1–4 h after ingesting nalmefene and again 12–18 h later. It appears that demonstrable increases in opioid tone occur at least transiently in a proportion of oligo-amenorrheic athletes.
Effects of free radical scavengers on cytokine actions on islet cells
Authors: Yamada Kentaro , Inada Chizuko , Otabe Shuichi , Takane Naoko , Hayashi Hideki , Nonaka Kyohei
Published: June 2009

We investigated the effect of free radical scavengers on the actions of cytokines on islet cells. Interferon-γ and tumor necrosis factor-α reduced the nicotinamide adenine dinucleotide content of mouse islet cells; the combination of interferon-γ (4×105 U/I) and tumor necrosis factor-α (4×105 U/I) caused nicotinamide adenine dinucleotide reduction by ∼40%. Dimethyl urea and dimethyl sulfoxide prevented the decrease, whereas superoxide dismutase, catalase, and mannitol were not effective. Dimethyl urea and dimethyl sulfoxide protected islet cells from the synergistic cytotoxic action of interferon-γ and tumor necrosis factor-α. Major histocompatibility complex class II antigen induction by interferon-γ and tumor necrosis factor-α was also inhibited by dimethyl urea and dimethyl sulfoxide, but not by superoxide dismutase, catalase and mannitol. Since superoxide dismutase of a membrane-penetrable form attenuated the class II antigen induction, the inefficiency of superoxide dismutase, catalase and mannitol may be attributable to their inability to penetrate islet cells. These results suggest that the intracellular generation of free oxygen radicals is involved in islet cell cytotoxicity and class II molecule expression by interferon-γ and tumor necrosis factor-α, and that nicotinamide adenine dinucleotide reduction may be associated with islet cell dysfunction caused by the cytokines.
The facilitatory effect of N-methyl-D-aspartate on sexual receptivity in female rats through GnRH release
Authors: Hsu Chin , Lee Jau-Nan , Ho Mei-Ling , Cheng Bi-Hwa , Li Pi-Hseuh Shirley , Yu John Yuh-Lin
Published: June 2009

The purpose of this study was to examine whether N-methyl-D-aspartate affects the sexual receptivity of female rats. Monosodium L-glutamate was used as a neurotoxin to induce hypogonadal status. Matured normal and monosodium L-glutamate-treated rats were ovariectomized and implanted subcutaneously with estradiol capsules. One week later, lordosis responsiveness was observed before and 10 min after N-methyl-D-aspartate (40 mg/kg of BW, ip) administration. The results showed that N-methyl-D-aspartate caused a remarkable increase of lordosis quotient in control rats but not in monosodium L-glutamate-treated rats. Moreover, the possible action site of N-methyl-D-aspartate in the enhancement of receptivity was evaluated by the post-castrational LH rise, pituitary LH release in response to GnRH, and N-methyl-D-aspartate-evoked GnRH releasability. The results revealed that: (a) serum levels of LH in monosodium L-glutamate-treated rats were lower (p <0.01) than those of control rats after ovariectomy; (b) there was no significant difference of pituitary LH release responsiveness to GnRH test between two groups; and (c) N-methyl-D-aspartate-evoked LH release in monosodium L-glutamate-treated rats was similar to that in the control rats. In conclusion, N-methyl-D-aspartate may facilitate the sexual receptivity through stimulating GnRH release. The failure of N-methyl-D-aspartate in enhancing receptivity in monosodium L-glutamate-treated rats is probably due to the cellular damage by monosodium L-glutamate on specific areas responsible for lordosis.
In situ hybridization of arginine vasopressin (AVP) heteronuclear ribonucleic acid reveals increased AVP gene transcription in the rat hypothalamic paraventricular nucleus in response to emotional stress
Authors: Priou Anne , Oliver Charles , Grino Michel
Published: June 2009

The regulation of anterior pituitary adrenocorticotropin hormone (ACTH) secretion during stress involves several hypothalamic neurohormones, including arginine vasopressin (AVP). In situ hybridization techniques have been used to study the regulation of neuropeptide messenger ribonucleic acids in the hypothalamus. Owing to the relatively slow time course of the changes in cytoplasmic messenger ribonucleic acid concentrations, rapid alterations in the level of neuropeptide gene transcription could not be detected. Because of its rapid processing, the nuclear level of the heteronuclear ribonucleic acid should reflect the rate of its synthesis, namely the transcription of the gene. We have used in situ hybridization with a probe complementary to a portion of an intronic sequence of the rat AVP gene to study rapid changes in the level of AVP gene transcription during emotional stress. The specificity of our technique was demonstrated by the localization of the hybridization signals in the paraventricular nucleus, the supraoptic nucleus and the suprachiasmatic nucleus, and was confirmed by the nuclear localization of the labeling. Isolation and exposure of male rats to a novel environment induced an activation of the pituitary-adrenal axis and an increase in AVP heteronuclear ribonucleic acid concentrations in the paraventricular nucleus 2 h after the onset of the stress, suggesting that an increased AVP gene transcription may play a role in the activation of the pituitary-adrenal axis in response to emotional stress.
T cell receptor β chain gene polymorphisms in Graves' disease
Authors: Pickerill A Paul , Watson Phillip F , Tandon Nikhil , Weetman Anthony P
Published: June 2009

Graves' disease, or subgroups of such patients with thyroglobulin antibodies or HLA-DR3, have been associated with a restriction fragment length polymorphism of the T cell receptor β chain constant region gene but not all studies are in agreement. We have examined 58 patients with Graves disease and found no abnormal distribution of this polymorphism compared to 33 controls. There was also no significant association with the presence of thyroglobulin antibodies or HLA-DR3, even when the results were pooled with previously collected data (N=90 patients with TG antibody results and N = 128 patients with HLA-DR types). We also found no abnormal distribution of three polymorphisms of the T cell receptor β chain variable region genes, using probes which span over 600 kb of this complex. These results argue against an association of these allelic variations of the T cell receptor β chain with Graves' disease.
Normal calcitonin response to pentagastrin stimulation in patients with chronic renal failure
Authors: Escalada Javier , Teruel José L , Pavón Isabel , Vila Trinidad , Navarro Juan , Varela César
Published: June 2009

High calcitonin levels have been reported in chronic renal failure. To study the C cell response in patients with chronic renal failure, an intravenous bolus of pentagastrin was administered to 11 patients and 11 healthy subjects. Samples were obtained at 0,1,2, 3, 5 and 10 min for calcitonin assay. In order to detect only the active monomeric calcitonin, an immunoradiometric assay method was used. The influence of calcium, phosphate, alkaline phosphatase and intact parathyroid hormone was also evaluated. Although basal calcitonin levels were higher (p<0.01) in chronic renal failure (mean±sem: 10.1±2.9 pmol/l) versus healthy subjects (1.1±0.3 pmol/l), the area under the curve showed there to be no differences between the two groups. The rising branch of the area under the curve, employed as an expression of the C cell response capacity, showed no differences either (chronic renal failure vs healthy subjects: 5.6±2 vs 2.6±0.7 pmol l−1 min−1, p=0.28). In the chronic renal failure group, a positive correlation was found (r=0.625, p<0.05) between the rising branch of the area under the curve and parathyroid hormone. We conclude that monomeric calcitonin is increased in chronic renal failure, but C cells of the thyroid respond to pentagastrin, as they do in normal subjects. This finding is of great clinical importance when a patient with renal impairment is evaluated for medullary thyroid carcinoma. The calcitonin response to pentagastrin seems to be related directly to the degree of secondary hyperparathyroidism in chronic renal failure.
Effects of chronic heroin abuse on bone and mineral metabolism
Authors: Pedrazzoni Mario , Vescovi Pier P , Maninetti Letizia , Michelini Massimo , Zaniboni Giulio , Pioli Giulio , Costi Daniele , Alfano Francesco S , Passeri Mario
Published: June 2009

Though the chronic use of opiates can modify several body functions, only a few data are available on the effects of opioid drugs on mineral metabolism. We have examined the possible consequences of chronic opiate abuse on bone mass, bone turnover and calcium metabolism in 13 male chronic heroin users, examined 1–2 days after the last administration of the drug (group A), 14 former male heroin addicts, examined 4–24 months after drug discontinuation (group B), and 22 healthy, age- and sex-matched control subjects. In group A, the vertebral bone mineral density (measured by Dual-Photon Absorptiometry) was significantly lower (p <0.05) than in the control subjects, despite similar values of total body bone mineral, lean body and fat mass. Blood-ionised calcium and urinary calcium and hydroxyproline were significantly increased (p<0.01), whereas parathyroid hormone was lower than in controls (p<0.01). Bone alkaline phosphatase and osteocalcin, however, were not significantly different from the control values. LH and testosterone levels were low (p <0.01 vs controls). In contrast, group B subjects did not show significant differences from the control group. The chronic abuse of opioid drugs may be associated with altered bone metabolism and reduced trabecular bone mass, attributable, at least in part, to gonadal deficiency. These alterations seem reversible after drug discontinuation.
Growth of the dominant follicle is similar to normal in patients with gonadotrophin-stimulated polycystic ovary syndrome exhibiting monofollicular development during a decremental dose regimen
Authors: Schoot Dick C , Hop Wim C , Pache Thierry D , de Jong Frank H , Fauser Bart CJM
Published: June 2009

The aim of this study was to investigate the late follicular phase of seven gonadotrophin-treated patients with polycystic ovary syndrome (PCOS) exhibiting monofollicular growth and to compare developmental characteristics with the dominant follicle in seven regularly cycling control women. Daily serum follicle-stimulating hormone (FSH) levels in patients with PCOS decreased more rapidly compared to controls (−0.3±0.2 IU/day in controls versus −0.7±0.4 IU/day in PCOS; p<0.02). No statistically significant differences were seen in daily increase (30% in controls and PCOS) and mean peak levels (825±94 pmol/l in controls versus 937±231 pmol/l in PCOS) of oestradiol (E2) serum levels when comparing both groups. Mean daily growth of the dominant follicle (1.7±0.4 mm in controls versus 1.9±0.6 mm in PCOS) was not significantly different. It is concluded from the present study that in patients with PCOS treated with gonadotrophin plus adjuvant gonadotrophin-releasing hormone agonist, development of a single follicle can occur using a decreasing dose regimen resulting in decreasing serum FSH levels. In addition, growth and oestrogen production by the dominant follicle in PCOS is not significantly different from follicle growth under normal conditions.
Restoration of gallbladder contractility after withdrawal of long-term octreotide therapy in acromegalic patients
Authors: Shi Yi-Fan , Zhu Xian-Feng , Harris Alan G , Zhang Jin-Xi , Deng Jie-Ying
Published: June 2009

We sought to examine how the discontinuation of octreotide in long-term octreotide-treated acromegalic patients affects the well-documented side-effect of cholelithiasis. In 14 acromegalic patients, serum growth hormone levels, insulin-like growth factor I levels and percentage of relative gallbladder contractility were measured prior to and after the discontinuation of octreotide. Compared to pretreatment values, the basal growth hormone and 5-h growth hormone profiles were 36% and 24%, and 60% and 56% at the end of 1 and 2 weeks, respectively. Octreotide was found to be eliminated completely from the serum within 3 days after its withdrawal. In all of six patients who did not develop gallstones, the percentage relative gallbladder contractility normalized within 1 week. In eight patients who developed gallstones, four of them had restoration of normal contractility within 2 weeks. Our results show that upon withdrawal of octreotide, gallbladder contractility returns to normal while growth hormone suppression persists for a longer period of time. Therefore, discontinuation of octreotide therapy may allow for the clearance of stagnated bile and hence decrease the incidence of cholelithiasis in acromegalic patients receiving long-term therapy.
Effect of triptorelin (Decapeptyl®) combined with heparin on estradiol levels in MCF-7 mammary cancer cells after incubation with estrone sulfate
Authors: Pasqualini Jorge R , Blumberg-Tick Joelle , Nguyen Bach-Lien
Published: June 2009

The effects of triptorelin (Decapeptyl®) and heparin, alone or in combination, on the intracellular concentration of estradiol (E2) after incubation of estrone sulfate (E1S) with the MCF-7 mammary cancer cells was investigated. Although heparin (10 mg/l culture medium) or Decapeptyl® (5×10−7 or 5 × 10−5mol/l) did not affect the levels of radioactive E2 after incubation with [3H]E1S, the combination of Decapeptyl® and heparin significantly decreased the radioactive uptake and the intracellular concentrations of [3H]E2. In the absence of Decapeptyl® and heparin incubations with E1S, the resulting E2 concentration (in nmol/kg DNA±sd) was 558±44; after heparin (10 mg/l) plus Decapeptyl® (5× 10−7 or 5× 10−5 mol/l) the values were 389±55 and 165±18, respectively. It is concluded that Decapeptyl® with heparin can decrease very significantly the conversion of E1S to E2 in MCF-7 cells, an observation that suggests new possibilities for the control of E2 in hormone-dependent breast cancer.
Effects of galanin on growth hormone release in isolated cultured rat somatotrophs
Authors: Lindström Per , Sävendahl Lars
Published: June 2009

Several studies suggest that galanin stimulates growth hormone release through effects on the hypothalamus. It is not known if galanin has acute effects directly on the somatotrophs. We now find that 0.5 μmol/l galanin stimulates growth hormone release within the first minute of exposure in isolated, purified, cultured male rat somatotrophs. The effect persisted for 15 min and was reversible when galanin was omitted. Galanin reduced the effect of 1 nmol/l growth hormone-releasing hormone (hGHRH(1–29)) on growth hormone release. Galanin stimulated 45Ca efflux from pre-labelled cells but had no effect on 86Rb efflux (tracer for potassium). The findings support the fact that galanin can stimulate growth hormone release directly at the level of the somatotrophs. The cellular mechanisms for the effect of galanin probably differ from those of growth hormone-releasing hormone.
Hyperfunctioning unilateral adrenal macronodule in three patients with Cushing's disease: hormonal and imaging characterization
Authors: Abs Roger , Nobels Frank , Verhelst Johan , Chanson Philippe , Mahler Charles , Corthouts Bob , Blockx Pierre , Beckers Albert
Published: June 2009

We aimed to investigate the dynamics of adrenocorticotropin (ACTH) and cortisol secretion in pituitary-dependent Cushing's syndrome with bilateral macronodular adrenal hyperplasia presenting as a single adrenal macronodule, and to determine the imaging characteristics of this syndrome. Three female patients were studied. Plasma ACTH and serum cortisol secretion were studied by determining their rhythmicity and pulsatility and their responses to the administration of ovine corticotropin-releasing factor, thyrotropin-releasing hormone, metyrapone, tetracosactrin, insulin and dexamethasone. Techniques used to localize the anatomical lesion were bilateral simultaneous inferior petrosal sinus sampling, magnetic resonance examination of the pituitary, computed tomography (CT) scanning and [75Se]cholesterol scintigraphy of the adrenal glands. Plasma ACTH and serum cortisol levels were measured using a commercial radioimmunoassay and an immunoradiometric assay. The ACTH and cortisol pulse number and amplitude were calculated using established computer software. In all three patients ACTH and cortisol secretory dynamics fulfilled the requirements for diagnosis of pituitary-dependent Cushing's syndrome. A close relationship between ACTH and cortisol pulses also favored a pituitary dependency. Study of the amplitude of cortisol pulses classified two patients in the group of hypopulsatile Cushing's disease. Adrenal CT scanning demonstrated the presence of a large single nodule. [75Se]Cholesterol scintigraphy showed bilateral radionuclide uptake, although mostly localized over the adrenal nodule. All patients underwent successful trans-sphenoidal hypophysectomy. Over a period of 1 year, a slow shrinkage of the adrenal nodule was observed in two patients, while no change in volume was observed in one patient. Demonstration of an adrenal macronodule on CT scanning in patients with Cushing's syndrome is in itself insufficient to allow the diagnosis of hypercorticism due to a unilateral adrenal adenoma. Additional dynamic endocrine testing, inferior petrosal sinus sampling and imaging techniques such as [75Se]cholesterol scintigraphy remain necessary to reach a correct diagnosis.