bluuebunny/crossref_metadata_2025 huggingface dataset:
Underfeeding of rat mothers during the first two trimesters of gestation does not alter insulin action and insulin secretion in the progeny
Authors: Portha Bernard , Kergoat Micheline , Blondel Olivier , Bailbe Danielle
Published: December 2008

Portha B, Kergoat M, Blondel 0, Bailbe D. Underfeeding of rat mothers during the first two trimesters of gestation does not alter insulin action and insulin secretion in the progeny. Eur J Endocrinol 1995;133:475–82. ISSN 0804–4643

It has been suggested that impaired insulin action and/or insulin secretion in adult mammals could be a consequence of severe food restriction during fetal life. We have determined to what extent glucose homeostasis and insulin action are modified in male offspring of rats undernourished only during the first two trimesters of pregnancy. Pregnant females then were assigned to one of the following three experimental conditions. Rats in the first group had their food restricted to 50% of their pregnancy intake during the first 2 weeks of pregnancy, after which they were allowed to eat ad libitum. Rats in the second group were similarly restricted during the first 2 weeks, but beginning on day 14 of gestation were pair-fed to control rats until weaning on day 21 after birth. Such an experimental group was introduced because we observed that food-restricted mothers increased their food intake significantly above control levels in the last week of gestation and maintained this increase into the first postnatal week, when they were returned to ad libitum feeding on day 14 of gestation. Control rats (third group) were given access to food ad libitum throughout pregnancy and lactation. Offspring of mothers in the three groups are referred to as food-restricted/ad libitum refed (RA), food-restricted/ pair-refed (RP) and control (C) groups, respectively. From 6 weeks of age, RA males ate significantly more food and gained significantly more weight on a standard laboratory diet than control offspring. Maternal overeating after the restriction appears to be a necessary component in the aetiology of these effects because pair-refeeding mothers blocked the subsequent hyperphagia of male offspring fed the stock diet (RP group). In both the RA and RP groups, basal plasma glucose and insulin levels were not significantly different from those in control offspring and no alteration of the tolerance to intravenous glucose and the in vivo insulin secretory response to glucose was detected. Moreover, glucose utilization and endogenous glucose production were not impaired when measured either in the basal situation (postabsorptive state) or in hyperinsulinaemic conditions. Therefore, early food restriction of the mothers exerts no adverse effect upon insulin secretion and insulin action in the male offspring.

B Portha, Lab. Physiopathology of Nutrition, CNRS URA 307, Université D. Diderot, Paris 7, 2 place Jussieu, Tour 33, 75251 Paris Cedex 05, France
Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas
Authors: Luts Lena , Bergenfelz Anders , Alumets Jan , Sundler Frank
Published: December 2008

Luts L, Bergenfelz A, Alumets J, Sundler F. Peptide-containing nerve fibres in normal human parathyroid glands and in human parathyroid adenomas. Eur J Endocrinol 1995;133:543–51. ISSN 0804–4643

There are only a few studies on the innervation of the human parathyroid glands and the content of neurotransmitters. We therefore studied the occurrence and distribution of peptide-containing and adrenergic nerve fibres and the coexistence pattern of neuromessengers by immunocytochemistry in normal (unaffected) and adenomatous parathyroid glands from patients undergoing surgery for parathyroid adenoma. The unaffected parathyroid glands had a moderate-to-rich supply of nerve fibres and terminals containing two general neuronal markers, protein gene product 9.5 (PGP 9.5) and synaptophysin, neuropeptide Y (NPY) and tyrosine hydroxylase (TH). They were seen close to blood vessels and, occasionally, among the endocrine cells. Only a few nerves contained calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), substance P (SP) and pituitary adenylate cyclase-activating peptide (PACAP). The general density of innervation, using PGP 9.5 and synaptophysin as markers, varied greatly among the different adenomas examined. This applied also to the density of fibres and terminals containing specific types of messengers. Some of the tumours had a rich supply of TH- and NPY-containing nerve fibres, while others contained only few scattered fibres. The CGRP-containing fibres varied from moderate in number to no detectable fibres. The PACAP-, SPand VIP-containing fibres were always very few or not detectable. It is not inconceivable that the wide variation in general density of the innervation and frequency of peptide-containing nerves among individual parathyroid adenomas is of significance for their hormone secretory behaviour.

Lena Luts, Department of Medical Cell Research, Biskopsgatan 5, S-223 62 Lund, Sweden
Evidence for oestrogenic regulation of heat shock protein expression in human endometrium and steroid-responsive cell lines
Authors: Tang Pei-Zhong , Gannon Michael J , Andrew Alison , Miller David
Published: December 2008

Tang P-Z, Gannon MJ, Andrew A, Miller D. Evidence for oestrogenic regulation of heat shock protein expression in human endometrium and steroid-responsive cell lines. Eur J Endocrinol 1995;133:598–605. ISSN 0804–4643

Gene amplification with target-specific primers (reverse-transcription polymerase chain reaction (RTPCR)) was used to monitor the relative expression of oestrogen and progesterone receptor mRNAs alongside the mRNAs for heat shock proteins HSP 90α, HSP 90β and HSP 70a in normal samples of human endometrial tissue over the whole menstrual cycle and in short-term cultures of steroidresponsive (T47-D) and unresponsive (HRT-18) cell lines exposed to oestradiol and progesterone over a 24-h incubation period. In endometrium, oestrogen and progesterone receptors followed the expected patterns of expression at the protein level during the menstrual cycle and also showed a positive correlation of expression with each other throughout (r = 0.514). Of the HSPs only HSP 90α expression correlated positively with oestrogen receptor (r = 0.687), while HSP 70a expression, which peaked in the late secretory stage, displayed a significantly inverse correlation with HSP 90β expression (r = −0.526). All p values < 0.05. In T47-D cell cultures, oestrogen receptor expression was stimulated transiently by oestradiol (10−7 mol/l) and more persistently by progesterone (10−7 mol/l). Progesterone receptor expression was depressed by progesterone and weakly stimulated by oestradiol. HSP 70a and HSP 90α expression were stimulated by oestradiol. Progesterone generally depressed HSP 90α expression and simultaneous addition of both oestradiol and progesterone to the culture medium was antagonistic to HSP 90α expression. No clear effect of agonist addition on HSP mRNA expression was apparent in the HRT-18 cultures. A possible mechanism for observed oestrogenic effects on HSP expression is put forward.

David Miller, Institute of Pathology, Department of Clinical Medicine, Algernon Firth Building, University of Leeds, Leeds, LS2 9JT UK
Effects of 22-oxacalcitriol on bone metabolism in vitro: comparison with calcitriol—Effects of 22-oxacalcitriol on osteoclast-like cell formation and bone-resorbing activity
Authors: Kanatani Masanori , Sugimoto Toshitsugu , Kaji Hiroshi , Kano Junichi , Chihara Kazuo
Published: December 2008

Kanatani M, Sugimoto T, Kaji H, Kano J, Chihara K. Effects of 22-oxacalcitriol on bone metabolism in vitro: comparison with calcitriol. Eur J Endocrinol 1995;133:618–25. ISSN 0804–4643

22-Oxacalcitriol (OCT), a synthetic vitamin D3 analog, can mimic the ability of calcitriol to differentiate leukemia and skin cells, to enhance the immune response and to suppress parathyroid hormone secretion, but has much less calcemic activity than that of calcitriol. The mechanism of this selective action remains not fully understood, and the actions of OCT on bone metabolism are little known. The present study was, therefore, designed to investigate the effects of OCT and calcitriol on: the proliferation and functions of osteoblastic MC3T3-E1 cells; osteoclast-like cell formation from hemopoietic blast cells in the absence of stromal cells as well as from unfractionated bone cells in the presence of stromal cells; bone resorption; and the proliferation of MC3T3-E1 cells via monocytes. 22-Oxacalcitriol and calcitriol inhibited [3H]thymidine (TdR) incorporation, alkaline phosphatase activity and collagen synthesis of MC3T3-E1 cells to a similar degree. Both OCT (10−10–10−8 mol/l) and calcitriol significantly and similarly stimulated osteoclast-like cell formation from both hemopoietic blast cells and unfractionated bone cells. 22-Oxacalcitriol (10−10 and 10−8 mol/l) significantly stimulated bone resorption, although to a slightly lesser degree than did calcitriol. Human monocyte-conditioned medium (CM) significantly stimulated TdR incorporation into MC3T3-E1 cells. On the other hand, CM obtained from monocytes treated with calcitriol (10−10–10−8 mol/l) significantly inhibited TdR incorporation in a dose-related fashion, whereas CM obtained from monocytes treated with OCT (10−10–10−8 mol/l) significantly stimulated TdR incorporation in a dose-related fashion. Thus, the actions of OCT on osteoblasts, osteoclast precursor cells and mature osteoclasts, possibly via osteoblasts, are mostly similar to those of calcitriol in vitro. The low activity of OCT in mobilizing calcium from bone in vivo, therefore, appears to be due to some other factor. OCT and calcitriol differed only in their indirect effects on the proliferation of osteoblasts via monocytes, possibly through modulating the release from monocytes of local factors that affect bone remodelling.

Toshitsugu Sugimoto, Third Division, Department of Medicine, Kobe University School of Medicine, Kobe, Japan
Effects of growth hormone and insulin-like growth factor I on the immune system
Authors: Auernhammer Christoph J , Strasburger Christian J
Published: December 2008

Auernhammer CJ, Strasburger CJ. Effects of growth hormone and insulin-like growth factor I on the immune system. Eur J Endocrinol 1995;133:635–45. ISSN 0804–4643

Growth hormone-releasing hormone (GHRH). growth hormone (GH), prolactin (PRL) and insulin-like growth factor I (IGF-I) are synthesized and secreted by various immunocompetent cells. In addition, GHRH, GH, PRL and IGF-I receptors are expressed on immune cells. Growth hormone, PRL and IGF-I stimulate the proliferation of immunocompetent cells and modulate humoral and cellular immune functions, i.e. immunoglobuline secretion of B cells, thymulin secretion of thymic epithelial cells, natural killer cell activity, phagocytosis, oxidative burst and killing capacity of neutrophils and macrophages. No clinically significant cellular or humoral immunodeficiency has been found in GH-deficient patients. However, several immunological parameters and functions are altered in GH-deficient patients when compared to normal controls. The data available to date indicate that endocrine and pleiotropic para- and autocrine mechanisms of action are involved in a neuropeptide immune network, including GH PRL and IGF-I as modulators of immune function.

Christian J Strasburger, Medizinische Klinik, Klinikum Innenstadt der LMU, Ziemssenstr. 1, 80336 Munich, Germany
Growth hormone receptor: structure and signal transduction
Authors: Postel-Vinay Marie-Catherine , Finidori Joëlle
Published: December 2008

Postel-Vinay M-C, Finidori J. Growth hormone receptor: structure and signal transduction. Eur J Endocrinol 1995;133:654–9. ISSN 0804–4643

The growth hormone receptor (GHR) belongs to the superfamily of transmembrane proteins that includes the prolactin receptor and a number of cytokine receptors. Two forms exist for the GHR: the full-length membrane-bound human receptor is a protein of 620 amino acids with a single transmembrane region; and the GH binding protein (GHBP) is a short soluble form corresponding to the extracellular domain of the full-length receptor. In rodents, GHBP is encoded by a specific mRNA of 1.2–1.5 kb, whereas in man and other species GHBP is believed to result from proteolytic cleavage of the membrane receptor. Growth hormone binding protein prolongs the half-life of GH but other functions for GHBP remain to be demonstrated. Recombinant GHBP complexed to human GH shows a 2:1 stoichiometric crystal structure. Growth hormone-induced dimerization of the cell surface GHR appears to be a prerequisite for biological activity of the hormone. JAK2 has been identified as a tyrosine kinase associated with GHR and other receptors of the superfamily. Binding of GH to its receptor results in dimerization of the GHR, phosphorylation of JAK2 and of the GHR. Other substrates for JAK2 have to be identified. Transcription factors belonging to the STAT (signal transducers and activators of transcriptions) family are involved in the transcriptional effects of GH. The activity of mutants of the GHR has been measured in functional tests to identify sequences of the cytoplasmic domain of the receptor that are important for signal transduction. A proline-rich sequence, called Box I, conserved among members of the receptor family has been shown to be crucial for GH effects on gene transcription, MAP kinase activity and cell proliferation. The C-terminal region of the GHR is required for tyrosine phosphorylation of the receptor and for a hormonal effect on gene transcription, whereas only 46 membrane proximal amino acids of the cytoplasmic domain are necessary for activation of JAK2 and transduction of the GH proliferative signal. Much work remains to be done to identify other protein kinases and signalling molecules involved in the mechanism of action of GH.

M-C Postel-Vinay, INSERM Unité 344, Faculté de Médecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
High-dose progesterone infusion in healthy males: evidence against antiglucocorticoid activity of progesterone
Authors: Allolio Bruno , Oremus Martin , Reincke Martin , Schaeffer Hans-Jörg , Winkelmann Werner , Heck Georg , Schulte Heinrich M
Published: December 2008

Allolio B, Oremus M, Reincke M, Schaeffer H-J, Winkelmann W, Heck G, Schulte HM. High-dose progesterone infusion in healthy males: evidence against antiglucocorticoid activity of progesterone. Eur J Endocrinol 1995;133:696–700. ISSN 0804–4643

High concentrations of unbound cortisol in late pregnancy have been explained by the antiglucocorticoid activity of high progesterone levels. To further test this hypothesis we studied the effect of high-dose progesterone on baseline and corticotrophin-releasing hormone (CRH)-induced hormone secretion in humans. In a double-blind crossover study eight healthy male volunteers received either progesterone (0.714 mg · kg−1 · h−1 for 60 min followed by a dose of 0.45 mg · kg−1 · h−1 over a total infusion time of 315 min) or vehicle as a continuous intravenous infusion. At 210 min a CRH test (0.1 μg/kg body weight as bolus iv) was performed. Within 30 min after the start of progesterone administration the serum progesterone level increased to 454 ± 31 nmol/l and remained in the range of third trimester pregnancy concentrations throughout the infusion period. During vehicle infusion the progesterone level remained in the normal range for healthy males and demonstrated a small but significant increase after CRH (1.52 ± 0.23 vs 0.74 ± 0.14 nmol/l; p < 0.01). However, baseline and CRH-stimulated serum cortisol and plasma adrenocorticotrophic hormone remained unaffected by high-dose progesterone. Moreover, unbound salivary cortisol also was not affected by progesterone, suggesting that there is no significant competition for transcortin binding sites. In conclusion, no antiglucorticoid activity was found after short-term administration of progesterone in males. These findings cast doubts on the concept that the alterations of the pituitary–adrenal axis in late pregnancy are induced by the antiglucocorticoid activity of high progesterone concentrations.

Bruno Allolio, Medizinische Universitätsklinik Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany
Effects of growth hormone overproduction on grip strength of transgenic mice
Authors: Wolf Eckhard , Wanke Rüdiger , Schenck Emanuel , Hermanns Walter , Brem Gottfried
Published: December 2008

Wolf E, Wanke R, Schenck E, Hermanns W, Brem G. Effects of growth hormone overproduction on grip strength of transgenic mice. Eur J Endocrinol 1995;133:735–40. ISSN 0804–4643

Growth hormone (GH) is used by athletes like bodybuilders to increase muscle strength and weight gain. On the other hand, chronic hypersecretion of GH in active acromegaly may result in outwardly hypertrophied but functionally weaker muscles. As a model for studying long-term effects of GH on muscle strength, we analysed transgenic mice (TM) carrying rat phosphoenolpyruvate carboxykinasebovine GH (PEPCKbGH) fusion genes, which are expressed in liver and kidney but not in skeletal muscle. Circulating GH levels in TM ranged between 0.5 and 3 μg/ml, resulting in increased (p <0.001) body weight (wt) as well as increased (p <0.01) weights of forelimb and hindlimb muscles. However, muscle weight/body wt ratios of TM were 16–20% smaller than in controls (p<0.05), Forelimb grip strength of hemizygous TM (16 males, 132 ± 45 days old, body wt = 56.8 ± 8.3 g; 32 females, 146 ± 38 days old, body wt = 54.9 ± 6.1 g) and non-transgenic controls (28 males, 127 ± days old, body wt = 40.5±2.9 g; 33 females, 126 ±47 days old, body wt = 32.1 ± 3.6 g) was determined using an automated grip strength meter. Data were computed by analysis of variance, taking into account effects of group, sex and age. Least-squares means estimated for the grip strength (N) of male TM (1.91) and controls (1.92) were significantly (p<0.05) greater than those of female TM (1.78) and controls (1.61). A significant difference between groups was only seen in females (p <0.01). Least-squares means estimated for grip strength/body wt ratios (N/10 g) of male (0.34) and female TM (0.33) were 29% and 35% lower than those of male (0.48) and female controls (0.51), respectively (p <0.001). In summary, long-term elevated GH levels in TM increased muscle weight less efficiently than body weight, and muscle strength did not increase proportionally with muscle weight.

Eckhard Wolf, Lehrstuhl für Molekulare Tierzucht und Haustiergenetik, Ludwig-Maximilians-Universität München, Würmtalstraβe 221, 81375 München, Germany
Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog
Authors: Fanciulli Giuseppe , Oliva Osvaldo , Tomasi Paolo A , Pala Alessandra , Bertoncelli Alba , Dettori Alessandra , Delitala Giuseppe
Published: December 2008

Fanciulli G, Oliva O, Tomasi PA. Pala A. Bertoncelli A, Dettori A, Delitala G. Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog. Eur J Endocrinol 1996:134:73–6. ISSN 0804–4643

Exogenous growth hormone (hGH) administration in humans attenuates the endogenous growth hormone (GH) response to some pharmacological stimuli: in particular, pretreatment with hGH completely blocks the serum GH response to growth hormone-releasing hormone. In order to evaluate the mechanism(s) whereby opioids induce GH secretion in man, we gave the following treatments to six healthy male volunteers: (a) IV saline: (b) a met-enkephalin analog G-DAMME 250 μg IV as a bolus at time ′: (c) hGH 2 IU as an IV bolus at time −180′; (d) G-DAMME as above, preceded by hGH as above. In our study. G-DAMME stimulated GH secretion both basally (peak 17.9 ± 6.0 ng/ml) and, to a lesser extent, after hGH pretreatment (6.0 ± 2.7 ng/ml). Since in our study G-DAMME was able to partially overcome the inhibitory effect of hGH administration, it is suggested that opioids act through an inhibition of somatostatin release and not through a GHRH-dependent pathway. However, an additional direct effect of hGH on pituitary somatotrophes cannot be excluded.

Giuseppe Delitala, Chair of Endocrinology, Viale S. Pietro 12, University of Sassari, 07100 Sassari. Italy
Long-term GnRH-agonist administration revealed a GnRHindependent mechanism stimulating FSH discharge in humans
Authors: Genazzani Alessandro D , Massolo Fausta , Ferrari Elena , Gandolfi Andrea , Petraglia Felice , Genazzani Andrea R
Published: December 2008

Genazzani AD. Massolo F. Ferrari E, Gandolfi A, Petraglia F, Genazzani AR. Long -term GnRH-agonist administration revealed a GnRH-independent mechanism stimulating FSH discharge in humans. Eur J Endorcrinol 1996:134:77–83. ISSN 0804–4643

The present study evaluated the FSH and LH episodic discharge in different physiopathological conditions undergoing chronic GnRH-agonist administration. Four girls with true precocious puberty and five postmenopausal women were administered GnRH-agonist (3.73 leuprolide acetate every 4 weeks: Takeda Italia, Rome, Italy) for at least 4 months. Plasma LH and FSH secretory profiles were assessed before and under GnRH-agonist administration (after 21 and 120 days). Pulsatility studies were conducted for 4 h in the girls and for 6 h in postmenopausal women, with blood sampling intervals of 10 min. Pubertal and postmenopausal patients showed the distinct episodic co-secretion of LH and FSH before GnRH-agonist administration: this co-secretion disappeared in both groups after 21 and 120 days of treatment. Moreover, while LH concentrations decreased to almost undetectable levels and LH episodic release disappeared. FSH plasma levels were only partially reduced and FSH episodic secretion was detectable in both groups. In conclusion, this study demonstrated that long-term GnRH-agonist administration blocked LH but not FSH episodic release. These data enforce the hypothesis that FSH episodic discharge might be dependent not only on hypothalamic GnRH, but also on a GnRH-independent stimulatory pathway.

Alessandro D Genazzani, Department of Obstetrics and Gynecology, University of Modena, Via del Pozzo 71, 41100 Modena, Italy
Recurrent miscarriage is associated with increased numbers of CD5/20 positive lymphocytes and an increased incidence of thyroid antibodies
Authors: Roberts Judith , Jenkins Carol , Wilson Rhoda , Pearson Charles , Franklin Ian A , MacLean Marjory A , McKillop James H , Walker James J
Published: December 2008

Roberts J. Jenkins C, Wilson R, Pearson C, Franklin IA, MacLean MA, McKillop JH, Walker JJ. Recurrent miscarriage is associated with increased numbers of CD5/20 positive lymphocytes and an increased incidence of thyroid antibodies. Eur J Endocrinol 1996;134:84–6. ISSN 0804–4643

The aim of this study was to determine whether recurrent miscarriage (three or more miscarriages, no live children) was associated with an increased incidence of autoantibodies. Five groups were enrolled into the study; healthy non-pregnant women, healthy first-trimester pregnant women, women suffering spontaneous abortion, those undergoing termination of pregnancy and those with a previous history of miscarriage. The number of total B cells and the numbers of the antibody producing B cell subset CD5+/CD20+ were determined for each group. Samples were tested for anticardiolipin antibodies, antinuclear antibodies and thyroid microsomal and thyroglobulin antibodies. The results showed that compared to normal pregnancy or spontaneous abortion, recurrent miscarriage was associated with a significant increase in the number of CD5+/20+ positive cells (0.8 ± 0.3 vs 0.5 ± 0.1 vs 1.1 ± 0.3 × 108/l: p < 0.001). These women were also found to have a higher incidence of thyroid antibodies, with four out of the 11 patients being positive for thyroid microsomal antibodies. These results suggest that there may be an association between autoimmunity and recurrent miscarriage.

R Wilson, Department of Medicine, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK
5α-Androstane-3α, 17β-diol and 5α-androstane-3α, 17β-diolglucuronide in plasma of normal children, adults and patients with idiopathic hirsutism: a mass spectrometric study
Authors: Wudy Stefan A , Wachter Ulrich A , Homoki Janos , Teller Walter M
Published: December 2008

Wudy SA. Wachter UA, Homoki J, Teller WM. 5α-androstane-3α, 17β-diol and 5α-androstane-3α, 17β-diol-glucuronide in plasma of normal children, adults and patients with idiopathic hirsutism: a mass spectrometric study. Eur J Endrocrinol 1996;134:87–92. ISSN 0804–4643

We investigated the developmental patterns of 5α-androstane-3α, 17β-diol (AD) and 5α-androstane-3α, 17β-diol-glucuronide (ADG) in plasma of normal children and adults of both sexes and in patients with idiopathic hirsutism using a physicochemical method: high-resolution gas chromatography/ mass spectrometry (HRGC/MS). In children below the age of 11 years, AD and ADG increased with age showing no differences between sexes (mean ±sd nmol/l): normal subjects 3–6 years: AD in females 0.08± 0.03. in males 0.07 ±0.03; ADG in females 0.15 ±0.05, in males 0.14± 0.04: normal subjects 7–10 years: AD in females 0.17 ± 0.03, in males 0.17 ± 0.07; ADG in females 0.59 ± 0.12, in males 0.47 ± 0.14. Thereafter, AD and ADG showed a greater increase in males (normal subjects 11–15 years: AD in females 0.24 ± 0.06, in males 0.41 ±0.14: ADG in females 1.47± 0.36. in males 3.36 ± 1.22). In adults, plasma levels did not overlap between females and males (AD in females 0.24 ±0.07. in males 0.99± 0.31; ADG in females 2.32 ± 0.68, in males 13.01 ± 3.05). 5α-Androstane-3β, 17β-diol-glucuronide discriminated better between sexes than AD. In idiopathic hirsutism, mean plasma concentrations of AD and ADG were higher than those of healthy females (ages 11–15 years: AD 0.31 ± 0.10. ADG 3.48 ± 2.00; ages > 16 years: AD 0.44 ± 0.27, ADG 6.46 ± 3.11). but 54% of patients had normal plasma concentrations of AD and 29% had normal ADG values. Thus, ADG reflected androgenicity better than AD. However, both metabolites were imperfect markers of androgenicity in idiopathic hirsutism. Therefore, our findings do not support the concept of increased 5α-reductase activity in all patients with idiopathic hirsutism.

Stefan A Wudy, Steroid Laboratory, First Department of Pediatrics, University of Ulm. D-89070 Ulm/Donau, Germany
Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents
Authors: Hasegawa Yukihiro , Hasegawa Tomonobu , Takada Makoto , Tsuchiya Yutaka
Published: December 2008

Hasegawa Y, Hasegawa T, Takada M, Tsuchiya Y. Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents. Eur J Endocrinol 1996;134:184–9. ISSN 0804–4643.

Serum levels of total insulin-like growth factor I (IGF-I) correlate with growth hormone (GH) secretory status and are a useful parameter in the diagnostic evaluation of GH deficiency. Serum total IGF-I levels represent the combined quantity of free or unbound IGF-I and IGF-I that is bound to specific IGF binding proteins. Free IGF-I (fIGF-I), which is postulated to be the bioactive fraction, accounts for only a small fraction of the total amount. We have recently developed a new immunoradiometric assay (IRMA) for plasma fIGF-I and have investigated fIGF-I in relation to GH status. The simple, non-extraction assay procedure involves the capture of unbound IGF-I by anti-IGF-I antibody coated to polystyrene beads and detection by a radiolabelled anti-IGF-I antibody directed to a separate epitope. Preliminary studies demonstrated that the f IGF-I IRMA does not measure IGF-I that is complexed to IGF-binding proteins and that the equilibrium between the free and bound fractions is not disturbed during the assay. Free IGF-I levels were compared to total IGF-I levels measured in the same IRMA after acid–ethanol extraction of the samples. Normal levels of fIGF-I from infancy through adulthood were found to have a close correlation with total IGF-I levels, with the lowest levels occurring in infancy and peak levels during puberty. Patients with complete GH deficiency had low levels of both fIGF-I and total IGF-I, with 94% and 100% of the levels below the 5th percentile for age, respectively. On the other hand, approximately 90% of patients with normal IGF binding protein-3 levels among partial GH deficiency and normal short children had free and total IGF-I levels above the 5th percentile for age. These data indicate that the clinical utility of plasma fIGF-I measurements is similar to measurements of total IGF-I in the evaluation of childhood GH deficiency.

Yukihiro Hasegawa, Division of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital, 1-3-1 Urnezono Kiyose, Tokyo 204, Japan
Proinsulin, C-peptide, and insulin in normal subjects during an 8-h hyperglycemic clamp
Authors: Hartling Svend G , Røder Michael E , Dinesen Bo , Binder Christian
Published: December 2008

Hartling SG, Røder ME, Dinesen B, Binder C. Proinsulin C-peptide, and insulin in normal subjects during an 8-h hyperglycemic clamp. Eur J Endocrinol 1996;134:197–200. ISSN 0804–4643

Increased concentrations of proinsulin immunoreactive material (PIM) absolutely or relative to insulin is a characteristic finding in patients with non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to test if 8 h or mild hyperglycemia (7–9 nmol/l in healthy subjects could induce a preferential secretion of PIM from B cells. Serum concentrations of insulin, C-peptide and PIM were measured every 10 min during the 8 h of continuous glucose infusion in nine normal-weight healthy subjects without diabetes among their first-degree relatives. After a gradual rise in B-cell peptides, a steady state was reached. From 4 to 8 h no further difference in insulin, C-peptide or PIM concentration was found. Fasting PIM/C-peptide and PIM/insulin ratios of 0.5% and 2.3% increased during the glucose clamp to levels of 1.4% and 7.6%, respectively. Neither testing the regression slope nor comparing individual time points showed any significant difference for the PIM/C-peptide ratio from 2 to 8 h and for the PIM/insulin ratio from 3 to 8 h. These results do not support the hypothesis that an increased glucose drive per se results in an altered B-cell function with increasing PIM/Cpeptide ratio. At least 8 h of mild hyperglycemia in healthy subjects does not progressively alter B-cell function.

Svend Hartling, Department of Internal Medicine, Sundby Hospital, Italiensvej 1, DK-2300 Sundby, Denmark
Androgen-dependent sex differences in the hypothalamic serotoninergic system
Authors: Borisova Nina A , Proshlyakova Evgeniya V , Sapronova Anna Ya , Ugrumov Michael V
Published: December 2008

Borisova NA, Proshlyakova EV, Sapronova AY, Ugrumov MV. Androgen-dependent sex differences in the hypothalamic serotoninergic system. Eur J Endocrinol 1996;134:232–5. ISSN 0804–4643

This study has attempted to fulfil our knowledge on the sex differences in the hypothalamic serotoninergic (5-HT) system in adult rats, and also to evaluate the role of neonatal androgens in the appearance of this sexual dimorphism. Such integrative characteristics of the 5-HT system as 5-HT content and specific uptake were estimated and compared in the anterior and middle hypothalami in intact adult females and males, as well as in neonatally castrated adult males. According to our data, the 5-HT content and [3H]5-HT specific uptake both in the anterior and middle hypothalami of intact females exceeded significantly those in intact males. Neonatal castration of males resulted in an increase of the 5-HT content and [3H]5-HT uptake in both hypothalamic regions up to their levels in intact females. Thus, the present study provides new information on the sex differences in the hypothalamic 5-HT system, which are apparently related to the neonatal masculinization of the hypothalamus.

Michael V Ugrumov, Institute of Developmental Biology, Russian Academy of Sciences, Vavilov str., Moscow 117808, Russia
New insights into pancreatic β-cell metabolic signaling in insulin secretion
Authors: Prentki Marc
Published: December 2008

Prentki M. New insights into pancreatic β-cell metabolic signaling in insulin secretion. Eur J Endocrinol 1996;134:272–86. ISSN 0804–4643

In recent years, it has become apparent that second messengers and factors other than ATP, metabolically sensitive KATP+ channels and Ca2+ play essential roles in nutrient-induced insulin release. This paper reviews the evidence in support of several new concepts and hypotheses in the field of β-cell signaling. These include in particular that: a rise in cytosolic Ca2+ is not sufficient to explain the kinetics and extent of secretion induced by glucose: variations in ADP, rather than ATP, regulate β-cell metabolism and the KATP+ channel; anaplerosis (the replenishment of the citric acid cycle with intermediates) is essential for β-cell activation; a shift from fatty acid oxidation to esterification is an important event in β-cell signaling; malonyl-CoA and long chain acyl-CoA esters may act as metabolic coupling factors; glycolytic oscillations underlie, in part, oscillations in electrical activity, cytosolic Ca2+ and insulin release. A metabolic model of fuel sensing that integrates the mode of action of all classes of nutrient secretagogues is proposed.

Marc Prentki, Department of Nutrition, University of Montreal, CP6128, Succ, Centre-Ville, Montreal, PQ H3C3J7, Canada
High frequency of endocrine autoimmunity in patients with sarcoidosis
Authors: Papadopoulos Konstantin I , Hörnblad Yngve , Liljebladh Harriet , Hallengren Bengt
Published: December 2008

Papadopoulos KI, Hörnblad Y, Liljebladh H, Hallengren B. High frequency of endocrine autoimmunity in patients with sarcoidosis. Eur J Endocrinol 1996;134:331–6. ISSN 0804–4643

Autoimmune diseases and sarcoidosis may be related and, especially, the association between sarcoidosis and autoimmune thyroid disease has long been recognized. The frequency and type of endocrine autoimmunity was examined in a series of Swedish patients with sarcoidosis. Of all patients (N = 89) with documented sarcoidosis attending the Department of Pulmonary Medicine between January 1980 and December 1991, 78 patients (44 males and 34 females; median age at the time of the study 48 years, range 22–81 years) were examined at the Department of Endocrinology, Malmö University Hospital, in the present study. Fifteen patients (19.2%) had clinical or serological evidence of endocrine autoimmunity. Two patients had Addison's disease, both with polyglandular autoimmune (PGA) syndrome type II; evidence of thyroid autoimmunity was found in 13 patients, eight with clinical autoimmune thyroid disease (ATD) (two with Graves' disease and six with autoimmune thyroiditis), of whom two had PGA syndrome type III, and five with isolated positive thyroid serology: two patients had insulin-dependent diabetes mellitus and one had premature ovarian failure. The frequencies of Addison's disease, clinical ATD and PGA syndrome type II were significantly higher compared with the frequencies found in the general population. In conclusion, a high frequency of endocrine autoimmunity in patients with sarcoidosis, occurring in about 20% of the cases, was demonstrated. Thyroid autoimmunity and polyglandular autoimmune syndromes occurred most frequently. Complex immunological and genetic mechanisms might explain the association of sarcoidosis and endocrine autoimmune diseases.

Bengt Hallengren, Department of Endocrinology, Malmö University Hospital, S-205 02, Malmö, Sweden
Prophylactic application of thyrostatic drugs during excessive iodine exposure in euthyroid patients with thyroid autonomy: a randomized study
Authors: Nolte Wilhelm , Müller Ralf , Siggelkow Heide , Emrich Dieter , Hüfner Michael
Published: December 2008

Nolte W, Müller R, Siggelkow H, Emrich D, Hüfner M. Prophylactic application of thyrostatic drugs during excessive iodine exposure in euthyroid patients with thyroid autonomy: a randomized study. Eur J Endocrinol 1996;134:337–41. ISSN 0804–4643

In a prospective, randomized study we examined the influence of prophylactic short-term thyrostatic therapy on thyroid iodine metabolism in patients with euthyroid autonomy undergoing elective coronary angiography. From a total of 1177 patients, 51 fulfilled the criteria of euthyroid autonomy before coronary angiography (negative thyrotropin-releasing hormone test, 10-min uptake of at least 1.2% 99mTc and no elevation of free thyroxine and free triiodothyronine indices) and were randomized into three groups: group I (N = 17) received 20 mg/day of thiamazole and group 2 (N = 17) received 900 mg/day of sodium perchlorate; thyrostatic therapy was begun on the day before angiography and continued for 14 days; group 3 (N = 17) served as controls without treatment. Parameters of thyroid function-free thyroxine (FT4) index and free triiodothyronine (FT3) index, thyrotropin (TSH) and delta-TSH–urine iodine excretion and 99mTc uptake were determined before and 30 days after coronary angiography. At the end of the study the mean FT4 index and FT3 index were elevated significantly in the control group compared with baseline values, but were still within the normal range. In contrast, the mean FT4 index and FT3 index remained unchanged in the treated groups. Four mild cases of hyperthyroidism were observed at the end of the study: two cases in the control group and one case in each of the treated groups. Thyrotropin suppression, urine iodine excretion and 99mTc uptake differed significantly between the treated groups and the control group. In the treated groups TSH suppression, urine iodine excretion and 99mTc uptake remained unchanged 30 days after coronary angiography compared with baseline values. In the control group the degree of TSH suppression and the level of urine iodine excretion increased (about twofold) significantly after coronary angiography, whereas 99mTc uptake decreased significantly (ca. 50%). In conclusion, short-term prophylactic thyrostatic therapy seems to have a protective effect against iodine excess in patients with euthyroid autonomy. However, mild hyperthyroidism could not be prevented in some cases. Probably a combination therapy of thiamazole and perchlorate would be more effective.

Wilhelm Nolte, Department of Gastroenterology and Endocrinology, Medizinische Klinik, Robert-Koch-Straße 40, 37075 Göttingen, Germany
Aggressive thyroid cancer associated with toxic nodular goitre
Authors: Hayes Frances J , Sheahan Kieran , Heffernan Andrew , McKenna T Joseph
Published: December 2008

Hayes FJ, Sheahan K, Heffernan A, McKenna TJ. Aggressive thyroid cancer associated with toxic nodular goitre. Eur J Endocrinol 1996:134:366–70. ISSN 0804–4643

Reports of concurrent thyrotoxicosis and thyroid cancer have appeared in the last three decades. While most of the tumours have been clinically inconsequential, it has been suggested that thyroid carcinomas arising in patients with Graves' disease tend to behave aggressively, while those associated with toxic nodular goitre follow a more benign course. We report a contrary clinical experience with four cases of thyrotoxicosis associated with metastatic thyroid cancer, two of which were fatal. All four patients had toxic nodular goitre. Thyroid eye signs were uniformly absent. Two patients had received 131I therapy; none had other history of irradiation to the head or neck. Antimicrosomal and antithyroglobulin antibodies were absent in all four patients. Thyroid-stimulating immunoglobulin, which was measured in one patient, was also absent. Histopathological examination of the resected thyroid glands revealed two papillary cancers, one mixed anaplastic/papillary and one anaplastic cancer. All four patients had cervical node involvement and one had pulmonary metastases, Both patients with anaplastic carcinoma succumbed to their disease within 6 months; neither of the patients with papillary cancer had disease recurrence after 2 and 4 years, respectively. The experience reported here of aggressive thyroid cancer associated with toxic nodular goitre may represent coincidence or, alternatively, it may represent the early recognition of a change in the natural history of toxic nodular goitre.

TJ McKenna, Department of Endocrinology & Diabetes Mellitus, St Vincent's Hospital, Elm Park, Dublin 4, Ireland
Influence of oestrous cycle on the pressor recovery following haemorrhage in anaesthetized Brattleboro rats
Authors: Morrissey Sinead E , Baden-Fuller Joanna , Murugananthan Nirodhini , whitehead Saffron A , Laycock John F
Published: December 2008

Morrissey SE, Baden-Fuller J. Murugananthan N, Whitehead SA, Laycock JF. Influence of oestrous cycle on the pressor recovery following haemorrhage in anaesthetized Brattleboro rats. Eur J Endocrinol 1996;134:379–85. ISSN 0804–4643

A sexual dimorphism in the pressor responsiveness to the neurohypophysial hormone vasopressin may be associated with a peripheral interaction between ovarian steroids and the neurohypophysial hormone. Indeed, the ovarian steroids may inhibit the vasopressin-dependent component of the pressor response to haemorrhage. The present study examined the recovery of the arterial blood pressure following a single large 2%v/w) haemorrhage in anaesthetized male Long Evans (LE) rats and females of the same strain during either pro-oestrous or di-oestrous phases of the reproductive cycle. In addition the same recovery process was examined in Brattleboro rats with diabetes insipidus (BDI) lacking circulating vasopressin. All BDI rats had an impaired blood pressure recovery following haemorrhage compared with male rats of the parent LE strain, and this was irrespective of sex or stage of the oestrous cycle. While the blood pressure recovery was more impaired in both groups of BDI female rats than in the males of the same strain during the first 20 min after haemorrhage (both comparisons p < 0.001: ANOVA), there was no difference between the recoveries of the female rats in pro-oestrus or di-oestrus. In contrast a significantly impaired blood pressure recovery was observed in female LE rats at pro-oestrus, when circulating ovarian steroid concentrations are raised, compared with male (p < 0.001; ANOVA) and di-oestrous (p < 0.02; ANOVA) rats of the same strain. Heart rate responses to haemorrhage showed strain differences, with LE rats having initial decreased heart rates followed by a recovery process, while the heart rate responses of BDI rats increased immediately. The novel use of the female Brattleboro rat in this study provides evidence for the existence of an important inhibitory interaction between ovarian steroids and vasopressin during the blood pressure recovery phase following haemorrhage, and indicates a possible direct influence of gonadal steroids on the recovery process.

JF Laycock, Department of Physiology, Charing Cross & Westminster Medical School, Fulham Palace Rd, London W6 8RF, UK
Angiotensin II receptors: protein and gene structures, expression and potential pathological involvements
Authors: Clauser E , Curnow KM , Davies E , Conchon S , Teutsch B , Vianello B , Monnot C , Corvol P
Published: December 2008

Clauser E, Curnow KM, Davies E, Conchon S, Teutsch B, Vianello B, Monnot C, Corvol P. Angiotensin II receptors: protein and gene structures, expression and potential pathological involvements. Eur J Endocrinol 1996;134:403–11. ISSN 0804–4643

Two distinct types of cell-surface angiotensin II receptors (AT1 and AT2) have been defined pharmacologically and cDNAs encoding each type have been identified by expression cloning. These pharmacological studies showed the AT1 receptors to mediate all the known functions of angiotensin II in regulating salt and fluid homeostasis. Further complexity in the angiotensin II receptor system was revealed when homology cloning showed the existence of two AT1 subtypes in rodents and in situ hybridization and reverse transcription-polymerase chain reaction analyses showed their level of expression to be regulated differently in different tissues: AT1A is the principal receptor in the vessels, brain, kidney, lung, liver, adrenal gland and fetal pituitary, while AT1B predominates in the adult pituitary and is only expressed in specific regions of the adrenal gland (zona glomerulosa) and kidney (glomeruli). Expression of AT1A appears to be induced by angiotensin II in vascular smooth-muscle cells but is inhibited in the adrenal gland. Preliminary analysis of the AT1 promoters is also suggestive of a high degree of complexity in their regulation. Investigation of a potential role for altered AT1 receptor function has commenced at a genetic level in several diseases of the cardiovascular system. No mutations affecting the coding sequence have been identified in Conn adenoma and no linkage has been demonstrated with human hypertension by sib-pair analysis. None the less, certain polymorphisms that do not alter the protein structure have been found to be associated with hypertension and to occur at an increased frequency in conjunction with specific polymorphisms in the ACE gene in individuals at increased risk for myocardial infarction. Further characterization of the regions of the AT1 gene that regulate its expression are therefore needed. The physiological importance of the AT2 gene product still remains a matter of debate.

E Clauser, INSERM U36, Collège de France, 3 rue d'Ulm, 75005 Paris, France
Gonadal function after multimodality treatment in men with testicular germ cell cancer
Authors: Palmieri G , Lotrecchiano G , Ricci G , Spiezia R , Lombardi G , Bianco AR , Torino G
Published: December 2008

Palmieri G, Lotrecchiano G, Ricci G, Spiezia R, Lombardi G, Bianco AR, Torino G. Gonadal function after multimodality treatment in men with testicular germ cell cancer. Eur J Endocrinol 1996;134:431–6. ISSN 0804–4643

We evaluated gonadal function in 63 patients with testicular cancer both within 1 month of unilateral orchiectomy before further treatment (pretreatment) and 3 years after treatment discontinuation (post-treatment). Sixteen patients underwent orchiectomy alone (group 1), nine patients underwent infradiaphragmatic radiotherapy (group 2) and 28 patients received four cycles (group 3) and 10 patients received six cycles (group 4) of cisplatin-based chemotherapy (cisplatin, vinblastine and bleomycin—PVB, or cisplatin, etoposide and bleomycin—PEB), Pretreatment semen analyses showed reduced sperm cell density, motility and impaired morphology of spermatozoa in all four groups (p>0.05). At the same time elevated estradiol and decreased serum follicle-stimulating hormone (FSH) levels in 28.5% of subjects were correlated with high serum beta human chorionic gonadotropin concentrations. Semen analyses revealed the lowest values for all parameters after infradiaphragmatic radiotherapy. Sperm cell count, motility and morphology were significantly better in patients treated with orchiectomy alone or with a conventional dose of chemotherapy than in the groups that received radiotherapy or high doses of chemotherapy (p < 0.05). We also observed a correlation between serum FSH values and sperm cell density for both pretreatment and post-treatment in every group of patients (p<0.05). Persistent subclinical Leydig cell dysfunction in groups treated with radiotherapy or high doses of chemotherapy was expressed by increased basal luteinizing hormone levels (78% of patients in group 2 vs 60% of patients in group 4) (p < 0.05) and by normal testosterone serum values (89% of patients in group 2 vs 80% of patients in group 4). Spermatogenesis and Leydig cell function are, therefore, persistently impaired in the majority of testicular cancer patients treated with radiotherapy or with more intensive chemotherapy.

G Palmieri, Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Facoltà di Medicina e Chirurgia, Università "Federico II", Via S Pansini 5, 80131 Napoli, Italy