bluuebunny/crossref_metadata_2025 huggingface dataset:
Secretion pattern of immunoreactive inhibin in men
Authors: Brennemann Wolfgang , Sommer Lieselotte , Stoffel-Wagner Birgit , Bidlingmaier Frank , Klingmüller Dietrich
Published: December 2008

Brennemann W, Sommer L, Stoffel-Wagner B, Bidlingmaier F, Klingmüller D. Secretion pattern of immunoreactive inhibin in men. Eur J Endocrinol 1994;131:273–9. ISSN 0804–4643

Chronological changes in serum concentrations of inhibin, a gonadal glycoprotein hormone, were studied in healthy male volunteers (age 24–27 years). Secretion profiles of immunoreactive inhibin (ir-inhibin) were compared with those of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone. Blood samples were collected every 15 min for 24 h. Serum inhibin concentrations were measured by a two-site immunoenzymatic assay with antibodies raised against distinct epitopes of the recombinant 1–32 amino acids of the α-subunit of human inhibin. The normal range for men was 0.79–3.1 U/l × 10−3, the sensitivity of the assay was 0.1 U/l × 10−3 (cv: within-assay, 6.8%; between-assay, 8.2%). Luteinizing hormone and FSH were measured by immunoradiometric assay and testosterone by radioimmunoassay. Secretion profiles of inhibin and testosterone were tested for diurnal variations by cosinor rhythmometry. Highest ir-inhibin concentrations were observed in the morning at 08.00 h, with peak values of 2.45–3.20 U/l × 10−3. During the evening and the night, ir-inhibin levels were relatively low; lowest concentrations were observed between 01.00 h and 02.00 h at night: 1.20–1.86 U/l × 10−3. Highest testosterone levels were observed in the morning (20.5–36.6 pmol/I), lowest concentrations were detected at night (7.35–12.6 pmol/l). Cosinor rhythmometry supported the suggestion that there is a clear circadian secretion of ir-inhibin and testosterone, respectively. The secretion pattern of ir-inhibin was analyzed by the Cluster pulse analysis computed algorithm, which identified four to seven inhibin pulses per day, depending on the person under observation. A significant correlation could be observed between median testosterone and ir-inhibin concentrations (r = 0.449, p < 0.001). In conclusion, ir-inhibin and testosterone in healthy male volunteers follow a clear diurnal rhythm. Moment to moment changes of ir-inhibin can be observed in all secretion profiles investigated. A probable physiological role for pulsatile inhibin secretion is not yet clarified.

Dietrich Klingmüller, Institut für Klinische Biochemie, Universität Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany
Interleukin 1β, tumor necrosis factor-α and interleukin 6 decrease nuclear thyroid hormone receptor capacity in a liver cell line
Authors: Wolf Matthias , Hansen Nils , Greten Heiner
Published: December 2008

Wolf M, Hansen N, Greten H. Interleukin 1β, tumor necrosis factor-α and interleukin 6 decrease nuclear thyroid hormone receptor capacity in a liver cell line. Eur J Endocrinol 1994;131:307–12. ISSN 0804–4643

Many of the acute inflammatory responses in critical illness are mediated by tumor necrosis factor-α (TNF-α), interleukin 1/3 (IL-1β) and interleukin 6 (IL-6). Furthermore, these cytokines are involved in mediating the characteristic changes of thyroid function during acute disease known as non-thyroidal illness. In the present studies we investigated in vitro whether TNF-α, IL-1β and IL-6 modify nuclear thyroid hormone receptor (TR) capacity and/or affinity. Regulation of TR synthesis was studied in the human hepatoma cell line Hep-G2. Subconfluent cells were incubated with recombinant cytokines in serum-free medium. Nuclear extracts were prepared by high-salt extraction of cell nuclei. Binding assays were performed with [125I]-triiodothyronine; bound and free hormone were separated by filtration. Interleukin 1β decreased TR capacity in a dose-dependent manner. Compared with unstimulated cells, the TR capacity was reduced to 87.9 ± 3.9% (p < 0.05), 80.1 ± 3.9% (p < 0.01) and 72.1 ± 5.1% (p < 0.01) after incubation with 0.1,1.0 and 100 μg/l IL-1β respectively. Interleukin 6 and TNF-α significantly reduced receptor capacity only at concentrations of 10 μg/l or higher and the magnitude of the reduction was lower than with IL-1β. The TR capacity was reduced to 81.2 ± 2.3% (p < 0.01) and 83.2 ± 6.6% (p < 0.05) after stimulation with 10 μg/l IL-6 or TNF-α. respectively. TR affinity was not altered significantly after stimulation with any of the cytokines. In conclusion, we present evidence that the capacity of hepatic nuclear TRs is regulated by IL-1β. IL-6 and TNF-α. As cellular reaction to thyroid hormone stimulation depends on the number of nuclear TRs, this mechanism may serve to restrict catabolic effects of thyroid hormones during acute illness.

M Wolf, Medizinische Kern- und Poliklinik, Universitäts-Krankenhaus Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany
Follicle-stimulating hormone regulation of inhibin α-subunit mRNA in staged rat seminiferous tubules
Authors: Kaipia Antti , Penttilä Tarja-Leena , Toppari Jorma
Published: December 2008

Kaipia A, Penttilä T-L, ToppariJ. Follicle-stimulating hormone regulation of inhibin α-subunit mRNA in staged rat seminiferous tubules. Eur J Endocrinol 1994;131:323–9. ISSN 0804–4643

Steady-state levels of inhibin-α and -βB mRNAs are higher in stages II–VI of the seminiferous epithelial cycle than in stages VII–VIII We investigated follicle-stimulating hormone (FSH) regulation of inhibin α-subunit mRNA in stages II–VI and VII–VIII to study whether the stage specificity is due to differential hormonal regulation by FSH. Follicle-stimulating hormone caused a significant increase of inhibin-α mRNA levels in both stages during a 20-h incubation. The mechanism of the FSH effect was studied further in stages VII-VIII. Maximal stimulation of the inhibin-α mRNA level was achieved with 100 μg/l FSH, dibutyryl-3′,5′-cyclic adenosine monophosphate (db-cAMP, 0.2 mmol/l) and Spadenosine-3′,5′-monophosphothionate (Sp-cAMPS, 10 μmol/l) (a cAMP agonist). The presence of RpcAMPS (200 μmol/l) (a cAMP antagonist) abolished the stimulation, Rp-cAMPS alone had no effect. inhibin-βB mRNA levels in stages VII–VIII were not affected by FSH, db-cAMP, Sp-cAMPS or Rp-cAMPS. Phorbol 12-myristate 13-acetate (100 nmol/l) had no effect on inhibin-α or -βB mRNA levels. Actinomycin D abolished the stimulatory effect of FSH on inhibin-α mRNA expression. In conclusion, FSH stimulated inhibin-α mRNA expression similarly both in stages II–VI and VII–VIII of the seminiferous epithelial cycle and the stimulation in stages VII–VIII was cAMP-mediated.

Jorma Toppari, University of Turku, Institute of Biomedicine, Department of Physiology, Kiinamyllynkatu 10, FIN-20520 Turku, Finland
Variable biological activity of thyroid-stimulating hormone
Authors: Beck-Peccoz Paolo , Persani Luca
Published: December 2008

Beck-Peccoz P, Persani L. Variable biological activity of thyroid-stimulating hormone. Eur J Endocrinol 1994;131:331–40. ISSN 0804–4643

Thyroid-stimulating hormone (TSH), like the other pituitary glycoprotein hormones, is produced and secreted as a mixture of isoforms, the majority of which represent differences in oligosaccharide structure and possess different bioactivity. When samples are quantified simultaneously by immunometric assay and bioassay, the ratio between bioactivity (B) and immunoreactivity (I) may serve as an index of the overall potency of TSH. Variations of the TSH B/I ratio have been documented in both physiological and pathological conditions associated with alteration of the two most important mechanisms controlling TSH synthesis and secretion, i.e. TRH release and the thyroid hormone feedback system. Major examples of this assumption are the low TSH bioactivity found in samples from patients lacking TRH and thus bearing a hypothalamic hypothyroidism, and the enhanced bioactivity that is invariably found in TSH from patients with thyroid hormone resistance. Moreover, variations of TSH bioactivity have been recorded in normal subjects during the nocturnal TSH surge, in normal fetuses during the last trimester of pregnancy, in patients with primary hypothyroidism and in patients with TSH-secreting pituitary adenoma and non-thyroidal illness. In conclusion, the secretion of TSH molecules with altered bioactivity plays an important pathogenetic role in various thyroid disorders, while in some particular physiological conditions the bioactivity of TSH may vary in order to adjust thyroid hormone secretion to temporary needs.

Paolo Beck-Peccoz, Istituto di Scienze Endocrine, Ospedale Maggiore IRCCS, Via F. Sforza 35, 1-20122 Milano, Italy
Recombinant growth hormone and insulin-like growth factor I do not alter gonadotrophin stimulation of the baboon testis in vivo
Authors: Crawford Bronwyn A , Handelsman David J
Published: December 2008

Crawford BA, Handelsman DJ. Recombinant growth hormone and insulin-like growth factor I do not alter gonadotrophin stimulation of the baboon testis in vivo. Eur J Endocrinol 1994;131:405–12. ISSN 0804–4643

In vitro studies indicate a physiological role for insulin-like growth factor I (IGF-I) in paracrine regulation of testicular function and recent clinical studies suggest a potential role for growth hormone (GH) and/or IGF-I in the treatment of hypogonadotrophic states in males. This study aimed to examine the effects of pretreatment with recombinant human GH (rhGH) or rhIGF-I on the response to gonadotrophins of the non-human primate testis in vivo. Using a balanced Latin square design with repeated measures, six prepubertal male hamadryas baboons (Papio hamadryas hamadryas) were treated in a cross-over sequence for periods of 18 days with daily im injections of rhGH (0.4 IU·kg−1 · day−1), rhIGF-I (0.1 mg·kg−1 · day−1) or saline with a 2-week washout period between each treatment. A single im injection of hCG (1500 IU) increased serum testosterone (p = 0.0002) but neither rhGH nor rhIGF-I influenced the timing or magnitude of this response (p > 0.5). A single im dose of FSH (75 IU) stimulated immunoreactive inhibin (p = 0.01) but also was unaffected in magnitude or timing by pretreatment with rhGH or rhIGF-I (p> 0.2). Circulating IGF-I levels were increased independently by hCG (p = 0.01) and FSH (p < 0.0001) administration. These findings indicate that neither GH nor IGF-I pre-treatment enhance acute gonadal responses to gonadotrophin stimulation of the prepubertal non-human primate testis in vivo. These findings suggest that GH or IGF-I treatment of hypogonadotrophic men without somatotrophin deficiency is unlikely to be beneficial.

David J Handelsman, Andrology Unit, Royal Prince Alfred Hospital, Departments of Medicine and Obstetrics and Gynaecology, University of Sydney, Sydney 2006, Australia
Serum thyroglobulin in hospitalized chronic geriatric patients: its relationship to age, non-thyroidal illness, goitre and thyroid dysfunction in a follow-up study
Authors: Szabolcs István , Bernard Wolfdieter , Horster Franz A
Published: December 2008

Szabolcs I, Bernard W, Horster FA. Serum thyroglobulin in hospitalized chronic geriatric patients: its relationship to age, non-thyroidal illness, goitre and thyroid dysfunction in a follow-up study. Eur J Endocrinol 1994;131:462–6. ISSN 0804–4643

The objectives were to determine whether the serum thyroglobulin (TG) level is influenced by age or by non-thyroidal illness (NTI) of the aged, to investigate the constancy of the TG level after 1- and 2-month intervals and to investigate if the TG level could help to differentiate whether a subnormal thyrotrophin (TSH) level in a geriatric patient is caused by autonomous thyroid function, by age or by NTI. Two-hundred and twenty-six non-selected, chronic hospitalized patients over 60 years old and 82 healthy adults (20–40 years) participated in the study, and TSH, thyroxine, free thyroxine, triiodothyronine and TG were estimated. In 122 euthyroid geriatric patients with normal TSH the mean TG was normal (12.18 μg/l), but elevated (> 45 μg/l) TG values occurred more often than in healthy control persons (15/122 vs 3/82; χ(1)2 = 4.54, p = 0.03). The severity of the clinical state of the euthyroid patients had no influence on the TG values. If TG was measured after 1 and/or 2 months, in only 3/123 non-selected geriatric patients was there a fluctuation between the normal and abnormal range (versus fluctuation of the corresponding TSH values in 19/123 cases; χ(1)2 = 12.78, p = 0.0012). In 28 patients with subnormal TSH, a normal TG value had a predictive value of 0.6 to exclude autonomous thyroid function. Age and NTI of the geriatric patients have no significant influence on their mean TG level but high TG levels occur more often, even in euthyroid patients. The predictive value of TG is not sufficiently high to allow a clear differentiation of whether a subnormal TSH is caused by autonomous thyroid function or by the age process or by NTI. Nevertheless, the advantage of TG estimation to be more constant than TSH could be of benefit in screening studies.

I Szabolcs, HIETE I. Bel., Budapest, PO Box 112, 1389, Hungary
Influence of interleukin 1 and antihuman interleukin 1 receptor antibody on the growth and function of the thyroid gland in rats
Authors: Żerek-Mełeń G , Żylińska K , Fryczak J , Mucha S , Stępień H
Published: December 2008

Żerek-Mełeń G, Żylińska K, Fryczak J, Mucha S, Stępień H. Influence of interleukin 1 and antihuman interleukin 1 receptor antibody on the growth and function of the thyroid gland in rats. Eur J Endocrinol 1994;131:531–4. ISSN 0804–4643

Cytokines seem to influence the hypothalamo–pituitary–thyroid axis. We have studied the effect of different doses of interleukin 1α (IL-1α) and IL-1β (given twice daily ip) alone or together with antihuman IL-1 receptor antibody (aIL-1ra) on the proliferation of thyroid follicular cells and thyroid hormone levels in male Wistar rats. We have examined the influence of IL-1α and IL-1β at doses of 10.0, 1.0 and 0.1 μg/kg body wt of animal and aIL-1ra at a dose of 10.0 μg/kg body wt of animal. The incorporation of bromodeoxyuridine into thyroid follicular cell nuclei was used as an index of cell proliferation (labeling index: LI) and measured 24 h after the last of two injections of interleukin. Interleukin 1β, at all examined doses, increased thyroid follicular cell proliferation when compared to controls (p < 0.05), and a positive correlation between log of the dose of IL-1β used and LI (r = 0.62, p < 0.05) using Student's t-test was found. The administration of aIL-1ra alone also enhanced the thyroid follicular cell proliferation, whereas aIL-1ra used together with IL-1β exerted a less pronounced effect than each of these substances used separately (p < 0.05). Interleukin 1α at the dose of 10.0 μg/kg body wt increased the proliferation of thyroid follicular cells (p < 0.05). Thyroid hormone levels did not change in any of the experiments. These results suggest a regulatory role of IL-1 upon the proliferation of thyroid cells.

Henryk Stępień, Institute of Endocrinology, Medical University of Łódź, Dr. Sterling Str. 3, 91-425 Łódź, Poland
Pars tuberalis-specific cells in the ovine pituitary do express the common α-chain of glycoprotein hormones: an in situ hybridization and immunocytochemical study
Authors: Böckers TM , Bockmann J , Fauteck J-D , Kreutz MR , Bock R , Wittkowski W
Published: December 2008

Böckers TM, Bockmann J, Fauteck J-D, Kreutz MR, Bock R, Wittkowski W. Pars tuberalis-specific cells in the ovine pituitary do express the common α-chain of glycoprotein hormones: an in situ hybridization and immunocytochemical study. Eur J Endocrinol 1994;131:540–6. ISSN 0804–4643

The ovine pituitary pars tuberalis was investigated by electron microscopy, immunocytochemistry and non-radioactive in situ hybridization in order to characterize further the pars tuberalis-specific cells, whose functional role within the endocrine system is still enigmatic. Ultrastructural analysis revealed that, besides gonadotropic cells, the vast majority of cells in the ovine pars tuberalis show the typical characteristics of pars tuberalis-specific cells with clear signs of secretory activity. Immunocytochemical staining with a polyclonal antibody directed against the α-subunit of ovine glycoprotein hormones and in situ hybridization with an antisense oligonucleotide complementary to the α-subunit mRNA showed that the common α-chain of glycoprotein hormones is expressed in pars tuberalis-specific cells. Antibodies against the β-subunits failed to detect any of the known β-chains of pituitary glycoprotein hormones in these cells. The demonstration of the glycoprotein α-subunit in pars tuberalis-specific cells of the adult sheep supports previously existing evidence that these cells do secrete one or more glycoprotein hormones. With respect to the thyrotropin-β-like immunoreactivity in rats and hamsters, one might speculate that pars tuberalis-specific cells are a pluripotent cell type with a low secretory activity under basal conditions. Further studies should prove the hypothesis that a pre-existing mRNA pool in these cells can be used for sustained translation of glycoprotein hormones after physiological or pharmacological stimulation.

W Wittkowski, Institute of Anatomy, University of Münster, Vesaliusweg 2–4, 48 129 Münster, Germany
[111In-DTPA-D-Phe1]Octreotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment
Authors: Janson Eva Tiensuu , Westlin Jan-Erik , Eriksson Barbro , Ahlström Håkan , Nilsson Sten , Öberg Kjell
Published: December 2008

Tiensuu Janson E, Westlin J-E, Eriksson B, Ahlström H, Nilsson S, Öberg K. [111In-DTPA-D-Phe1]Octrotide scintigraphy in patients with carcinoid tumours: the predictive value for somatostatin analogue treatment. Eur J Endocrinol 1994:131:577–81. ISSN 0804–4643

This study was performed to evaluate whether the presence or absence of somatostatin receptors in malignant carcinoid tumours detected by [111In-DTPA-D-Phe1]octreotide scintigraphy can be used to predict response to somatostatin analogue treatment. Thirty patients were investigated, 28 with midgut carcinoid tumours and two with foregut carcinoid tumours. Twenty-seven patients showed pathological uptake in tumour lesions at scintigraphy: of these, 22 responded to somatostatin analogue treatment using octreotide, somatuline or octastatin, while five patients failed to respond. None of the three patients displaying negative scintigraphic investigations responded to treatment with somatostatin analogues. These results show a good correlation between the somatostatin receptor status and the patients' ability to respond to somatostatin analogue treatment (p = 0.014). We conclude that somatostatin receptor scintigraphy using [111In-DTPA-D-Phe1]octreotide can be used to select patients with malignant carcinoid tumours suitable for somatostatin analogue treatment and exclude those that will not benefit from such medication.

Eva Tiensuu Janson, Dept of Internal Medicine, University Hospital, S-751 85 Uppsala, Sweden
Exaggerated blood pressure response to angiotensin II in patients with Cushing's syndrome due to adrenocortical adenoma
Authors: Yasuda Gen , Shionoiri Hiroshi , Umemura Satoshi , Takasaki Izumi , Ishii Masao
Published: December 2008

Yasuda G, Shionoiri H, Umemura S, Takasaki I, Ishii M. Exaggerated blood pressure response to angiotensin II in patients with Cushing's syndrome due to adrenocortical adenoma. Eur J Endocrinol 1994:131:582–8 ISSN 0804–4643

We studied the roles played by the renin-angiotensin system in inducing hypertension in nine patients with Cushing's syndrome (CS) resulting from adrenocortical adenoma, and compared them with those in patients with primary aldosteronism (PA), renovascular hypertension (RVH) and essential hypertension (EH). In the CS group, each parameter, including serum potassium, plasma renin activity, plasma aldosterone, deoxycorticosterone and corticosterone concentrations, is within the normal range. However, plasma renin activity in the CS group was lower than that in the RVH group but higher than that in the PA group, and plasma aldosterone concentration was lower than that in each RVH or PA group. These findings indicated that the CS group had a different type of hypertension from that in either RVH or PA, in which the renin angiotensin system or mineralocorticoids play an important role in hypertension. Meanwhile, captopril (50 mg) administration either with or without indomethacin pretreatment decreased the mean blood pressure in the CS group, although captopril failed to change it in the PA group or in normal subjects. Furthermore, the pressor response to exogenous angiotensin II in the CS group was higher than that in the RVH or EH group, but was not different from that in the PA group. Thus, the hypertension in patients with CS due to adrenocortical adenoma appears to be mediated through a change in the renin-angiotensin system in the form of exaggerated pressor responses to angiotensin II.

G Yasuda, Second Department of Internal Medicine, Yokohama City University School of Medicine, 3-46 Urafune, Minami, Yokohama 232, Japan
Persistence of somatostatinergic tone in acromegaly
Authors: Attanasio Roberto , Cozzi Renato , Oppizzi Giuseppe , Dallabonzana Daniela , Chiodini Iacopo , Benini Zaira , Orlandi Paola , Liuzzi Antonio , Chiodini Pier Giorgio
Published: December 2008

Attanasio R, Cozzi R, Oppizzi G, Dallabonzana D, Chiodini I, Benini Z, Orlandi P, Liuzzi A, Chiodini PG. Persistence of somatostatinergic tone in acromegaly. Eur J Endocrinol 1995;132:27–31. ISSN 0804–4643

It is a matter of debate whether hypothalamic somatostatin (SRIH) secretion in acromegaly is preserved and still regulated by the physiological feedback mechanisms of growth hormone (GH) and insulin-like growth factor I. To gather further information on this, the reproducibility of plasma GH changes induced by growth hormone-releasing hormone (GHRH) administration was evaluated in 15 acromegalic patients. There was a highly significant correlation between the peak/basal ratio (P/B) GH response in the 15 patients administered GHRH on two separate occasions (r = 0.99, p <0.001). The test was performed also before and after the administration of drugs able to inhibit or stimulate hypothalamic SRIH release, by activating (pyridostigmine) or inhibiting (pirenzepine) cholinergic pathways, respectively. The GHRH-induced GH response (P/B = 2, range 1.1–26.1) was increased significantly by pyridostigmine pretreatment in 30 patients (P/B = 2.6, range 1.3–34.8; p = 0.0045). In nine out of 30 patients an increase of greater than 2sd of within-subject GHRH variability was observed in response to GHRH plus pyridostigmine when compared to GHRH alone. An inverse correlation (r = −0.37, p <0.05) was observed between GH response to GHRH alone and after pyridostigmine pretreatment. On the contrary, no change of GHRH-induced GH response was observed in 12 patients after pirenzepine pretreatment (P/B =1.9, range 1.1–5 and P/B = 2, range 1.3–6 without and after pirenzepine pretreatment, respectively). These data suggest that in acromegaly the somatostatinergic tone does not seem to fluctuate, and that it can be inhibited often by cholinergic pathway activation but not increased further by cholinergic suppression.

Roberto Attanasio, Divisione di Endocrinologia, Ospedale Niguarda, Piazza Ospedale Maggiore 3, 1-20162 Milano, Italy
Effect of 15-day treatment with growth-hormone-releasing hormone alone or combined with different doses of arginine on the reduced somatotrope responsiveness to the neurohormone in normal aging
Authors: Ghigo E , Ceda GP , Valcavi R , Goffi S , Zini M , Mucci M , Valenti G , Muller EE , Camanni F
Published: December 2008

Ghigo E, Ceda GP, Valcavi R, Goffi S, Zini M, Mucci M, Valenti G, Muller EE, Camanni F. Effect of 15-day treatment with growth hormone-releasing hormone alone or combined with different doses of arginine on the reduced somatotrope responsiveness to the neurohormone in normal aging. Eur J Endocrinol 1995;132:32–6. ISSN 0804–4643

It is well known that both spontaneous and growth hormone-releasing hormone (GHRH)-stimulated GH secretion undergo an age-related decrease; in addition, there is supportive evidence that the GH hyposecretory state of aging is of hypothalamic origin. The aims of the study in 35 normal elderly subjects (20 males and 15 females aged 65–89 years) were to verify whether the low somatotrope responsiveness to GHRH (1 μg/kg) can be primed by a daily GHRH treatment and whether the potentiating effect of both high intravenous (0.5 g/kg) and low oral (8 g) doses of arginine (ARG) on GH response to GHRH is maintained with time. In group A (N = 14) the GH response to GHRH on day 1 (AUC: 373.5 ± 78.5 μg·1−1·h−1) was unchanged after 7 (3720 ± 38 μg·1−1·h−1) and 15 days (377.9 ± 63.8 μg·1−1·h−1) of daily GHRH administration. In group B (N = 6) the GH response to GHRH co-administered with iv ARG on day 1 (1614.2 ± 146.2 μg · 1−1 · h−1) was higher (p < 0.05) than that of GHRH alone (group A) and persisted unchanged after 7 (1514.7±366.5 μg·1−1·h−1) and 15 days (1631.7 ± 379.1 μg · 1−1 · h−1) of treatment. In group C (N = 15) the GH response to GHRH co-administered with oral ARG on day 1 (950.6 ± 219.4 μg·1−1 · h−1) was higher (p < 0.03) than that of GHRH alone (group A) but lower (p < 0.05) than that to GHRH plus iv ARG (group B). It was unchanged after 7 (816.2 ± 208.5 μg·1−1 · h−1) and 15 days (760.4 ± 165.0 μg · 1−1· h−1) of treatment; these responses were still higher (p < 0.05) than that to GHRH alone. Insulin-like growth factor I levels were not modified by any of the treatments. In conclusion, our results demonstrate that in normal aging the low somatotrope responsiveness to GHRH is not improved by prolonged treatment with the neurohormone but it is enhanced by the combined treatment with ARG and this effect does not vanish after a 15-day treatment period. The effect of ARG is present even after a low oral dose, although less markedly than after a high intravenous dose.

F Camanni, Divisione di Endocrinologia, Ospedale Molinette, C. so Dogliotti 14, 10126 Torino, Italy
Bone mineral density in middle-aged women with Turner's syndrome
Authors: Sylvén Lisskulla , Hagenfeldt Kerstin , Ringertz Hans
Published: December 2008

Sylvén L, Hagenfeldt K, Ringertz H. Bone mineral density in middle-aged women with Turner's syndrome. Eur J Endrocrinol 1995;132:47–52. ISSN 0804–4643

Bone mineral density (BMD), bone mineral content and body composition were determined in 47 middle-aged (mean age 47.9 ± 1.1 years) women with Turner's syndrome. Bone mineral density was measured in the forearm, femoral neck and total body. The women investigated had a BMD lower than the normal mean. When expressed as Z scores (individual values compared to normal reference data matched for age, weight and sex), the median Z score of the total body was −1.23. When comparing women with the karyotype 45,X and mosaic women, the latter showed a higher BMD in all sites of measurement. Duration of hormonal replacement therapy (HRT) differed significantly between the mosaic and the 45,X women, with a longer duration in the mosaic group (20.7 ± 2 vs 12.1 ± 2.6 years; p < 0.01). The duration of HRT was found to be the more important factor to maintain bone mass, not the karyotype. Bone mineral density increased with years of HRT but not until after > 20 years of HRT could a significant difference be shown between the women with HRT ≤ 20 years and those with HRT > 20 years. No correlation was found between BMD and body weight, body fat or percentage body fat. Whether the osteopenia found in women with Turner's syndrome is similar to that found postmenopausally or is a specific form related to the chromosome aberration remains to be investigated further. The present data support a relation to estrogen deficiency.

Lisskulla Sylvén, Department of Woman and Child Health, Division for Obstetrics & Gynecology, Karolinska Hospital, S-171 76 Stockholm, Sweden
Thyroid cytotoxic antibodies in atrophic and goitrous autoimmune thyroiditis
Authors: Bogner Ulrich , Hegedüs Laszlo , Hansen Jens Molholm , Finke Reinhard , Schleusener Horst
Published: December 2008

Bogner U, Hegedüs L, Hansen JM, Finke R, Schleusener H. Thyroid cytotoxic antibodies in atrophic and goitrous autoimmune thyroiditis. Eur J Endocrinol 1995;132:69–74. ISSN 0804–4643

It is unknown whether in chronic lymphocytic thyroiditis the goitrous (Hashimoto's thyroiditis) and atrophic forms (primary myxedema) are variants of the same disease or different pathogenic entities. Conventional thyroid-related autoimmune parameters are unable to separate both diseases serologically. It is assumed that cellular and humoral cytotoxic events induce gland atrophy and thus should be detectable more often in non-goitrous than goitrous autoimmune thyroiditis. We determined antibody-dependent cell-mediated cytotoxicity in 67 patients with autoimmune thyroiditis, using a 51chromium-release assay against human thyroid cells. Thyroid volume had been measured by ultrasonography. Other thyroid-specific antibodies, like TSH binding-inhibiting antibodies, TSH function-blocking antibodies, thyroglobulin antibodies and thyroid peroxidase antibodies, were determined. Cytotoxic antibody activity was 20.5% (median, range 0–54.5%) in patients with autoimmune thyroiditis and 8.3% (median, range 0–18.4%) in controls (p < 0.0001). Analysis of cytotoxicity regarding thyroid size showed a high incidence of cytotoxic antibodies in atrophic disease (median thyroid volume 6 ml), where cytotoxic antibodies were detectable in 80% versus 39% (x2 = 9.6; p < 0.0001) in goitrous disease (median thyroid volume 36 ml). The specific lysis of 30% (median; 95% confidence limit 23.9–32.9) in non-goitrous thyroiditis patients was significantly higher than in goitrous patients (16.9%; 95% confidence limit 13.2–20.4) (p = 0.0006). Prevalence of thyroglobulin and thyroid peroxidase antibodies were equally distributed in both groups, with slightly higher levels of thyroid peroxidase antibodies in goitrous thyroiditis (p < 0.05). Both TSH binding-inhibiting and TSH function-blocking antibodies were rarely positive in either atrophic or goitrous disease. Our study shows for the first time a striking association of thyroid cytotoxic antibodies with the atrophic variant of autoimmune thyroiditis. We suggest that the occurrence of cytotoxic antibodies in the pathogenesis of chronic lymphocytic thyroiditis is the decisive event that favors the development of the atrophic rather than goitrous form of the disease.

Ulrich Bogner, Thyroid Research Unit, Freie Universität Berlin, Kurfürstenstr. 126, 10785 Berlin, Germany
Intrasellar bony spine, a possible cause of hypopituitarism
Authors: Abs Roger , Van Breusegem Ludo , Verhaert Griet , Smet Helena , Parizel Paul M
Published: December 2008

Abs R, Van Breusegem L, Verhaert G, Smet H, Parizel PM. Intrasellar bony spine, a possible cause of hypopituitarism. Eur J Endocrinol 1995;132:82–5. ISSN 0804–4643

A 39-year-old male patient with long-standing pituitary deficiency is reported. The onset of hypopituitarism was probably at about the age of 12 years, but diagnosis was not made until 6 years later. Since then he has received substitutive hormonal treatment and was referred with complaints suggestive of growth hormone deficiency. Retrospective study of a skull radiography performed at the age of 18 years revealed a calcified lesion in the sellar region. Additional radiological examinations showed the presence of a 9-mm intrasellar bony spine. Magnetic resonance examination showed a ventrally extending arrow-shaped bone deformation in continuity with the dorsum sellae, consisting of a hyperintense structure comparable with the intensity of the bone marrow of the dorsum and clivus. Computed tomography scanning confirmed in detail the morphology of the bony spine. This deformity probably represents the non-regressed cephalic segment of the notochord. Only in four reports has the existence of this congenital abnormality been described, but this is the first one in which hypopituitarism can be regarded as a complication of the intrasellar spine.

R Abs University of Antwerp, Department of Endocrinology, Universiteitsplein 1, B-2610 Wilrijk, Belgium
Augmentation of thyrotropin-induced iodide uptake in FRTL-5 cells by immunoglobulins containing blocking thyrotropin-receptor antibodies under NaCl-depleted conditions
Authors: Takeuchi Ryo , Kasagi Kanji , Hidaka Akinari , Miyamoto Shinichi , Misaki Takashi , lida Yasuhiro , Konishi Junji
Published: December 2008

Takeuchi R, Kasagi K, Hidaka A, Miyamoto S, Misaki T, lida Y, Konishi J. Augmentation of thyrotropin-induced iodide uptake in FRTL-5 cells by immunoglobulins containing blocking thyrotropin-receptor antibodies under NaCl-depleted conditions. Eur J Endocrinol 1995;132:109–17. ISSN 0804–4643

We have found recently that Graves' immunoglobulins (Igs) are more active under NaCl-free conditions to increase iodide uptake in FRTL-5 thyroid cells. The present study was designed to examine the effect of blocking-type thyrotropin (TSH)-receptor antibodies (TR-abs) in the same assay. FRTL-5 cells were incubated with crude Ig fractions from 13 patients with primary hypothyroidism having blocking TR-abs and 100 mU/l bovine TSH in NaCl-free Hanks' balanced salt solution (HBSS) supplemented with 274 mmol/l sucrose (HBBS(−)-sucrose to keep isotonicity for 3 days, followed by the determination of 60 min of 125I uptake in the cells. Thyrotropin alone increased the uptake to 3.3-to 5.2-fold of the basal. When the highest concentration (250 ml serum equivalent (eq.)/l) of the Ig was used, the TSH-stimulated 125I uptake was decreased to 0–42% in 11 of the 13 cases. When the lower concentrations (0.4–50 ml serum eq./l) were used, however, 125I uptake was enhanced (1.4- to 11.4-fold) unexpectedly in all 13 cases. Such an enhancement was specific to blocking TR-abs, because the effect was duplicated by the purified IgG but not by Igs from 10 healthy control subjects or from three TR-ab-negative hypothyroid patients. When Graves' Igs, instead of TSH, were used as a stimulator, the similar stimulatory effect of the Ig with blocking activity was observed on the 125I uptake induced by three Graves' Igs but not on the response to one Graves' Ig. These Igs alone displayed no stimulating activity. When isotonic 5H medium was used instead of HBSS(−)-sucrose, effects of these 13 Igs were only inhibitory on the TSH-stimulated 125I uptake. In summary, Igs containing blocking TR-abs from patients with primary hypothyroidism showed a variable effect on TSH- or Graves' Ig-induced 125I uptake, depending on their concentration and the presence of NaCl. Together with our recent reports that both stimulating and blocking TR-abs exist simultaneously in some patients, these observations suggest that the two types of TR-abs and TSH may play a more complicated role in disease expression than what has been suggested as merely a net activity.

Kanji Kasagi, Department of Nuclear Medicine, Kyoto University School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-01, Japan
Impaired response of atrial natriuretic peptide to acute water load in obesity and in anorexia nervosa
Authors: Baranowska Bogusława , Wasilewska-Dziubińska Elżbieta , Radzikowska Małgorzata , Płonowski Artur , Roguski Krzysztof
Published: December 2008

Baranowska B, Wasilewska-Dziubińska E, Radzikowska M, Płonowski A, Roguski K. Impaired response of atrial natriuretic peptide to acute water load in obesity and in anorexia nervosa. Eur J Endocrinol 1995;132:147–51. ISSN 0804–4643

Plasma atrial natriuretic peptide (ANP) concentrations were determined in basal conditions and after infusion of 1000 ml of 0.9% NaCl in women with anorexia nervosa, in normotensive obese women and in healthy women of the control group. Additionally, in the obese women and in the controls, plasma ANP was measured after iv injection of clonidine. Anorectic patients were investigated in the period of weight loss (mean deficit of body weight was 40%). The mean body mass index (BMI) in the obese women was 36.44 ± 0.36 kg/m2. Basal plasma ANP concentrations were significantly higher in both anorectic and obese women (p < 0.001 and p < 0.01, respectively). The response of ANP to acute water load was markedly blunted in anorexia nervosa and in obesity (Δ% = 232% in control group, 14% in anorexia nervosa and 21% in obesity. A significant increase of ANP was found after iv injection of clonidine in the control group and in obesity (p < 0.001 and p < 0.01, respectively). However, the increase of response (expressed as a percentage change) in obese patients was lower than that in the control group (Δ% = 64% and 199%, respectively). The response of ANP to α2-adrenergic stimulation was higher than to hemodynamic stimulus. Our results suggest that the disturbed control of neuropeptides and neurotransmitters as well as changes in peripheral metabolism may explain the impaired responsibility of ANP to hemodynamic stimuli in anorectic and obese patients.

Department of Neuroendocrinology, Medical Center of Postgraduate Education, Fieldorfa 40, 04-158 Warsaw, Poland
Lack of growth hormone response to acute administration of dexamethasone in anorexia nervosa
Authors: Scacchi Massimo , Invitti Cecilia , Pincelli Angela I , Pandolfi Claudio , Dubini Antonella , Cavagnini Francesco
Published: December 2008

Scacchi M, Invitti C, Pincelli AI, Pandolfi C, Dubini A, Cavagnini F. Lack of growth hormone response to acute administration of dexamethasone in anorexia nervosa. Eur J Endocrinol 1995;132:152–8. ISSN 0804–4643

High plasma growth hormone (GH) levels, associated with abnormal hormone responses to provocative stimuli, point to an altered GH secretion in anorexia nervosa. The GH-releasing effect of acutely administered glucocorticoids, firmly established in normal subjects, has not been reported in these patients. In this study, acute iv administration of 4 mg of dexamethasone, compared with saline, increased plasma GH in nine normal-weight women (AUC 848.2 ± 127.95 vs 242.8 ± 55.35 μg·l−1·min−1, p < 0.05, respectively) but was ineffective in 11 anorectic patients (AUC 3271.8 ± 1407.11 vs 2780.0 ± 1162.04 μg·l−1·min−1, NS). After dexamethasone, a significant lowering of plasma cortisol was observed in normal women (AUC 25367.0 ± 3128.43 vs 47347.1 ± 4456.61 nmol·l−1·min−1, after dexamethasone and saline, respectively, p < 0.05), but not in anorectic patients (AUC 77809.3 ± 8499.92 vs 78454.9 ± 7603.62 nmol·l−1·min−1, NS). In both groups, plasma adrenocorticotrophin (ACTH) displayed a significant decrease after dexamethasone (AUC 523.6 ± 92.08 vs 874.2 ± 115.03 pmol·l−1·min−1, p < 0.05, after dexamethasone and saline, respectively, in anorectic patients and 377.5 ± 38.41 vs 1004.9 ± 200.51 pmol·l−1·min−1, p < 0.05, in controls). However, when considering the hormonal decremental areas, a significant dexamethasone-induced ACTH inhibition, compared to saline, was evidenced in normal (ΔAUC –414.4 ± 65.75 vs 222.9 ± 42.40 pmol·l−1·min−1, p < 0.05) but not in anorectic women (ΔAUC –254.2 ± 96.92 vs 2.9 ± 132.32 pmol·l−1·min−1, NS). In conclusion, compared to normal subjects, anorectic patients do not display an increase of plasma GH levels and show a lower degree of inhibition of the hypothalamic–pituitary–adrenal axis following acute iv administration of dexamethasone. This observation broadens the array of the abnormal GH responses to provocative stimuli in anorexia nervosa and supports the existence, in these patients, of a decreased hypothalamic somatostatin secretion, although the possibility of a reduced tissue sensitivity to glucocorticoids cannot be excluded.

Francesco Cavagnini, 2nd Chair of Endocrinology, University of Milan, Istituto Scientifico Ospedale San Luca, Centro Auxologico Italiano, via Spagnoletto 3, 20149 Milano, Italy
Effect of growth hormone therapy in men with severe idiopathic oligozoospermia
Authors: Lee Kok-Onn , Ng Soon-Chye , Lee Pheng-Soon , Bongso Ariff T , Taylor Elizabeth A , Lin Ting-Kwong , Ratnam Shan S
Published: December 2008

Lee K-O, Ng S-C, Lee P-S, Bongso AT, Taylor EA, Lin T-K, Ratnam SS. Effect of growth hormone therapy in men with severe idiopathic oligozoospermia. Eur J Endocrinol 1995;132:159–62. ISSN 0804–4643

Some studies have suggested that growth hormone (GH) may enhance folliculogenesis in women, and similarly may enhance spermatogenesis in men with hypogonadotrophic hypogonadism. In this prospective open-controlled pilot study, we investigated the effect of daily subcutaneous GH for 5 months in 12 endocrinologically normal men with severe idiopathic oligozoospermia (< 10 million/ ml). All the men had normal karyotype and endocrine tests, including a GH response of > 20 000 mU/l to insulin hypoglycaemia. Nine men with similar sperm counts acted as controls. During treatment, each patient was examined monthly, asked for side effects and had glycosylated haemoglobin, glucose and blood counts monitored. Five semen samples were obtained in the 4 months before treatment, two samples per month during treatment and three samples after stopping treatment. The mean insulinlike growth factor I (IGF-I) was normal before treatment and 1 month after ending treatment, at 206 and 182 μg/l, respectively, but increased significantly during treatment to 444 μg/l (p < 0.0001, ANOVA). The mean (sd) sperm counts were 2.6 (2.5), 2.5 (3.7) and 2.3 (2.1) million/ml before, during and after GH treatment, respectively, and did not show any statistically significant differences (ANOVA). We conclude that GH does not increase or decrease sperm counts in men with severe idiopathic oligozoospermia.

K-O Lee, Division of Endocrinology, Department of Medicine, National University of Singapore, Kent Ridge, Singapore 0511
Urinary iodine excretion and individual iodine supplementation among elderly subjects: A cross-sectional investigation in the commune of Randers, Denmark
Authors: Pedersen Klaus M , Iversen Eigil , Laurberg Peter
Published: December 2008

Pedersen KM, Iversen E, Laurberg P. Urinary iodine excretion and individual iodine supplementation among elderly subjects. A cross-sectional investigation in the commune of Randers, Denmark. Eur J Endocrinol 1995;132:171–4. ISSN 0804–4643

Several studies have demonstrated that the iodine intake is relatively low in Denmark. However, the results are difficult to interpret because no information has been given on the frequency of individual iodine supplementation. We performed a cross-sectional study of elderly subjects living in the commune of Randers, Denmark. Urinary iodine excretion was measured in the 423 participants (185 males, 238 females) and a careful history was taken on any possible intake of supplementary iodine. The median urinary iodine excretion was 48.3 μg/g creatinine for the whole population (40.8 μg/g creatinine in males, 53.2 μg/g creatinine in females). In the part of the population that did not take iodine supplementation (46.7%) the median value was 36.1 μg/g creatinine (males 33.8; females 38.8). Regular iodine supplementation taken as an iodine-containing vitamin/mineral tablet was found in 30.8% of the population. This increased the urinary iodine excretion to a median level of 80.5 μg/g creatinine (males 62.0; females 88.0). The study shows that the basic iodine intake level is overestimated if individual iodine supplementation is not taken into account. Such supplementation may lead to median iodine excretion values that seem reasonable, even if the iodine intake of the part of the population not taking iodine (in this study, nearly half of the population) is low.

Klaus Pedersen, Department of Internal Medicine and Endocrinology, Aalborg Hospital, Reberbansgade, DK-9000 Aalborg, Denmark
Impaired natural killer cytotoxicity in peripheral blood mononuclear cells in Graves' disease
Authors: Marazuela Mónica , Vargas Juan A , Alvarez-Mon Melchor , Albarrán Fernando , Lucas Tomás , Durántez Alberto
Published: December 2008

Marazuela M, Vargas JA, Alvarez-Mon M, Albarrán F, Lucas T, Durántez A. Impaired natural killer cytotoxicity in peripheral blood mononuclear cells in Graves' disease. Eur J Endocrinol 1995;132:175–80. ISSN 0804–4643

We studied the natural killer (NK) activity of peripheral blood mononuclear cells (PBMC) in patients with Graves' disease (GD). Peripheral blood mononuclear cells from 20 untreated hyperthyroid patients with GD showed a significantly reduced NK activity against 51 Cr-labeled K562 cells (33.9 ± 15.9%), while in 32 euthyroid patients under antithyroid drug therapy, NK activity was similar to that of controls (46.9 ± 17.3 and 49.9 ± 20.2%, respectively). Furthermore, normalization of thyroid function with antithyroid drugs was associated with a significant increase and normalization of NK activity during the follow-up of nine GD patients (from 29.2 ± 17.9 to 48.1 ± 16.5%). This phenomenon could not be ascribed to a defective number of NK cells because the amounts of CD56 + and CD16 + cells in PBMC from both hyperthyroid and euthyroid GD patients were within normal ranges. Natural killer activity of PBMC from patients with toxic multinodular goiter was similar to that of normal controls (45 ± 12.8 to 49.9 ± 20%). No correlation was found between natural killer activity and serum levels of free thyroxine, TSH-inhibitory immunoglobulins, thyroidal antibodies to thryoglobulin and thyroidal microsomal antigen, dose or duration of antithyroid drug therapy. Natural killer activity from both controls and GD patients was enhanced in vitro by addition of recombinant interleukin 2 (IL-2), reaching control levels in hyperthyroid patients. These abnormalities were not associated with a defective IL-2 production by T cells, nor with a decreased IL-2R expression. We conclude that in untreated Graves' disease there is a decrease in NK cell activity in PBMC, probably dependent on the autoimmune process. Possible biological and clinical implications are discussed.

Monica Marazuela, Hospital de la Princesa, c/Diego de Léon 62, Madrid 28006, Spain
Identification of luteinizing hormone receptor binding inhibitor in bovine corpora lutea
Authors: Rathnam Premila , Lin Shou-qing , Saxena Brij B
Published: December 2008

Rathnam P, Lin S, Saxena BB. Identification of luteinizing hormone receptor binding inhibitor in bovine corpora lutea. Eur J Endocrinol 1995;132:213–17. ISSN 0804–4643

A 7000 g supernatant, obtained during the purification of luteinizing hormone (LH) receptor from bovine corpora lutea homogenate, was concentrated by ultrafiltration. The filtrate, containing < 50 000 molecular weight material, exhibited LH receptor binding inhibitor (LH-RBI) activity. The filtrate was ultrafiltered sequentially through Amicon PM-10, PM-30 and UM-2 filters to yield a LH-RBI-containing fraction in the higher molecular weight range of 30 000–10 000 and a LH-RBI-containing fraction in the lower molecular weight range of 10 000–1000. The higher molecular weight LH-RBI fraction was purified on Sephadex G-25 and the lower molecular weight LH-RBI fraction was purified on Sephadex G-50. Both the high- and the low-molecular-weight LH-RBI species inhibited the binding of 125I-labeled human chorionic gonadotropin (hCG) to bovine corpora lutea and to rat Leydig cell membrane receptors. Similarly, the production of testosterone by hCG-stimulated rat Leydig cells was inhibited in a dose–response manner by both the high- and the low-molecular-weight LH-RBI species. The LH-RBI activity in the low-molecular-weight species was stable at 4°C for up to 6 months and at temperatures up to 90°C for 15 mins, whereas the LH-RBI activity of the high-molecular-weight species was stable at 4°C for 15 months and unstable at 60°C after 15 min. The 7000 g supernatant provided a much-needed source to obtain larger than previously reported quantities of LH-RBI for isolation as well as for structure and function studies.

Brij B Saxena, Cornell Univ. Medical College, Rm A-267, 1300 York Ave, New York, NY 10021, USA