bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular effects of growth hormone replacement therapy in hypopituitary adults
Authors: Beshyah Salem A. , Shahi Manjit , Skinner Elizabeth , Sharp Patrick , Foale Rodney , Johnston Desmond G 
Published: December 2008

Beshyah SA, Shahi M, Skinner E, Sharp P, Foale R, Johnston DG. Cardiovascular effects of growth hormone replacement therapy in hypopituitary adults. Eur J Endocrinol 1994;130:451–8. ISSN 0804–4643
In the present study the effects of replacement with biosynthetic human growth hormone (GH) in a large group of hypopituitary adults on cardiac structure and function were investigated. Thirty-six GH-deficient, hypopituitary patients (17 males and 19 females; aged 19–67 years) on conventional replacement therapy without GH were studied. Twenty-nine of the patients had acquired hypopituitarism in adult life, mainly due to pituitary tumours. The design of the study was a prospective, randomized, double-blind placebo-controlled trial for 6 months. Growth hormone (17 patients) was given in a daily dose of 0.02–0.05 IU/kg body wt sc (or a placebo, 19 patients) according to the patients' tolerance. Other pituitary replacement treatment was unchanged. Resting and exercise electrocardiography using the Bruce protocol, two-dimensional echocardiography, Doppler ultrasound scanning and serum insulin-like growth factor I (IGF-I) were assessed at 0 and 6 months. Resting blood pressure was measured at 0, 1, 3 and 6 months. Serum IGF-I increased significantly on GH treatment (mean ± sd) GH: 293 ± 197 vs placebo: 82 ± 40 μg/l; p < 0.0001 at 6 months). Exercise time increased significantly on GH but not on placebo (GH: 8.45 ± 3.16 to 9.38 ± 2.42 min. sec, p < 0.01; placebo 9.08 ± 4.35 to 9.50 ± 4.14 min. sec, NS), although the change was not significantly different between the two. There was no change in the heart rate or the blood pressure either at rest or at the peak of exercise. No significant changes were observed in the left ventricular mass index, the left ventricular posterior wall thickness, the interventricular septal thickness, the ejection fraction or the cardiac output. Isovolumic relaxation time, a measure of the left ventricular diastolic function, decreased significantly on GH but not on placebo (GH: 98 ± 18 to 89 ± 11 ms, p = 0.03; placebo: 93 ± 17 to 89±14 ms, NS), although again the change on GH was not significantly different from that on placebo. There was no significant change in the left ventricular filling. No significant changes were observed in plasma levels of urea, electrolytes or creatinine on either GH or placebo. In conclusion, six months of GH replacement therapy in hypopituitary adults had favourable cardiovascular effects, including increased exercise tolerance and improved diastolic function.
Salem A Beshyah, Unit of Metabolic Medicine, St Mary's Hospital Medical School, Norfolk Place, London W2 IPG, UK
Effects of bright light on circadian patterns of cyclic adenosine monophosphate, melatonin and cortisol in healthy subjects
Authors: Lemmer Björn , Brühl Thomas , Witte Klaus , Pflug Burkhard , Köhler Wilfried , Touitou Yvan 
Published: December 2008

Lemmer B, Brühl T, Witte K, Pflug B, Köhler W, Touitou Y. Effects of bright light on circadian patterns of cyclic adenosine monophosphate, melatonin and cortisol in healthy subjects. Eur J Endocrinol 1994; 130:472–7. ISSN 0804–4643
Bright light is known as a strong zeitgeber on human circadian rhythms and influences several endocrine and neuroendocrine functions. In the present study we examined the influence of a 3-h bright light stimulus, given at different times during the day (morning or evening), on circadian patterns of cyclic adenosine monophosphate (cAMP), melatonin and cortisol. Two groups of synchronized healthy volunteers (lights on: 05.00–23.00 h) were exposed to bright light (2500 lux) for 3 h over 6 days either in the morning (05.00–08.00 h) or in the evening (18.00–21.00 h). The results showed a significant phase advance in the circadian rhythms of melatonin and cortisol when bright light was given in the morning but not when given in the evening. Rhythm in plasma cAMP basically was not affected by either light treatment.
Björn Lemmer, Zentrum der Pharmakologie, JW Goethe Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt/M, Germany
Tumor necrosis factor-α decreases thyrotropin-induced 5′-deiodinase activity in FRTL-5 thyroid cells
Authors: Ongphiphadhanakul Boonsong , Fang Shih Lieh , Tang Kam-Tsun , Patwardhan Nilima A , Braverman Lewis E 
Published: December 2008

Ongphiphadhanakul B, Fang SL, Tang K-T, Patwardhan NA, Braverman LE. Tumor necrosis factor-α decreases thyrotropin-induced 5′-deiodinase activity in FRTL-5 thyroid cells. Eur J Endocrinol 1994;130:502–7. ISSN 0804–4643
Tumor necrosis factor-α (TNF-α) exerts various effects on many cell types. Acute administration of TNF-α to rats decreases hepatic 5′-deiodinase activity (5′D-I) and TNF-α has been implicated in the pathogenesis of the low triiodothyronine syndrome in non-thyroidal illness in humans. The thyroid, liver and kidney are rich in 5′D-I. Unlike hepatic and renal 5′D-I, thyroid 5′D-I is regulated by thyrotropin. We have investigated the effects of TNF-α on 5D-I in FRTL-5 cells, a cultured rat thyroid follicular cell line. Tumor necrosis factor-α did not significantly affect basal 5′D-I but thyrotropin markedly increased 5′D-I (p < 0.001). This TSH-induced increase in 5′D-I was attenuated by TNF-α in a dose-dependent manner (p < 0.001). Enzyme kinetic analysis demonstrated that thyrotropin increased 5′D-I by increasing Vmax (p < 0.01) without significantly affecting Km. Likewise, TNF-α decreased the thyrotropin-induced 5′D-I by decreasing Vmax (p < 0.05) but not Km. The effect of TNF-α on thyrotropin-induced 5′D-I in FRTL-5 cells is probably mediated through post-thyrotropin-induced generation of cyclic adenosine monophosphate (cAMP) because TNF-α inhibited both dibutyryl cAMP (p < 0.001) and forskolin (p < 0.001)-induced increases in 5′D-I without affecting cAMP generation stimulated by thyrotropin. In conclusion, we have demonstrated that TNF-α inhibits thyrotropininduced 5′D-I activity in FRTL-5 cells by pathways distal to the generation of cAMP and that TNF-α may play a role in the modulation of the production of triiodothyronine by the thyroid gland. Furthermore, the increase in TNF-α observed in patients with the euthyroid sick syndrome may contribute to the low serum triiodothyronine observed in these patients, not only by inhibiting peripheral generation of triiodothyronine from thyroxine but also by decreasing thyroidal generation and subsequent secretion of triiodothyronine.
Lewis E Braverman, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA
Growth hormone treatment of rats with chronic diverting colostomy. Differential response on proximal functioning and distal atrophic colon
Authors: Kissmeyer-Nielsen P , Christensen H , Laurberg S 
Published: December 2008

Kissmeyer-Nielsen P, Christensen H, Laurberg S. Growth hormone treatment of rats with chronic diverting colostomy. Differential response on proximal functioning and distal atrophic colon. Eur I Endocrinol 1994;130:508–14. ISSN 0804–4643
Diversion of colon from the fecal stream leads to profound intestinal atrophy. After diverting colostomy for 4 weeks, female rats were treated with biosynthetic human growth hormone (b-hGH; 2.0 mg.kg−1 body wt.day−1) in order to investigate whether b-hGH could reverse atrophic changes in distal colon, with special reference to changes in morphometric composition, collagen content and biomechanical properties. Biosynthetic hGH treatment for 28 days stimulated growth of the muscularis propria of the defunctioned, atrophic colon (p < 0.05), whereas the mucosal atrophy was unaffected by the treatment. In colon proximal to the colostomy, however, b-hGH increased the colonic wet weight (p < 0.01), defatted dry weight (p < 0.005) and the collagen content (p < 0.05). Morphometric analysis showed that the growth increase was localized to the mucosa and the muscularis propria. In conclusion, fecal diversion alters the response of b-hGH treatment and indicates that the trophic effect of growth hormone on colonic mucosa is dependent on fecal bulk passage, whereas the trophic effect on muscularis propria is fully retained when colon is deprived of luminal nutrients.
Peter Kissmeyer-Nielsen, Surgical Research Unit, Department of Surgery L, Amtssygehuset, University Hospital of Aarhus, DK-8000 Aarhus C, Denmark
Influence of folliculo-stellate cells on biphasic luteinizing hormone secretion response to gonadotropin-releasing hormone in rat pituitary cell aggregates
Authors: Allaerts Wilfried , Tijssen Ans MI , Jeucken Pieter HM , Drexhage Hemmo A , de Koning Jurrien 
Published: December 2008

Allaerts W, Tijssen AMI, Jeucken PHM, Drexhage HA, de Koning J. Influence of folliculo-stellate cells on biphasic luteinizing hormone secretion response to gonadotropin-releasing hormone in rat pituitary cell aggregates. Eur J Endocrinol 1994;130:530–9. ISSN 0804–4643
Anterior pituitary cells cultured as three-dimensional cell aggregates and incubated with gonadotropin-releasing hormone (GnRH) show a biphasic pattern of luteinizing hormone (LH) release when steroid-free bovine follicle fluid is added to the culture medium. Initially, the GnRH-induced LH release is low (lag-phase response), but LH release increases during further incubations with GnRH (primed-state response). Also, in aggregates of dispersed cells from long-term ovariectomized rats cultured for 2 days in the presence of 1% bovine follicle fluid, a low initial LH responsiveness to GnRH could be restored. Cycloheximide was found to block the induction of the primed state, indicating the protein synthesis dependency of GnRH self-priming. In aggregates from gonadotroph-enriched cell populations obtained by velocity sedimentation in a bovine serum albumin gradient, addition of 1% bovine follicle fluid to the culture medium also restored a biphasic pattern of GnRH-induced LH release. However, co-culturing the gonadotroph-enriched cell aggregates with a folliculo-stellate (FS) cell-enriched population resulted in the attenuation of the differences in LH secretion rate between early and late responses to GnRH. The present example of the attenuation by folliculo-stellate cells of pituitary hormone secretion responses demonstrates that the cells regulate the cellular processes leading to a priming of the LH response to GnRH, rather than interfering with the access of GnRH to its receptor in gonadotrophs. Finally, it was found that stimulation of the adenylate cyclase enzyme with maximal effective doses of forskolin counteracted the inhibitory effect of bovine follicle fluid on the initial LH response to GnRH, but did not completely abolish the biphasic pattern of LH release. It is concluded that coupling to the adenylate cyclase enzyme is presumably involved in the LH surge inhibiting feedback action on the pituitary cells, but also other messenger pathways and intercellular interactions between pituitary cells may play a role in establishing a biphasic LH release at the pituitary level following GnRH administration.
W Allaerts, Dept. of Immunology, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands
Incidence of juvenile thyrotoxicosis in Denmark, 1982–1988. A nationwide study
Authors: Lavard Lene , Ranløv Ida , Perrild Hans , Andersen Ole , Jacobsen Bendt Brock 
Published: December 2008

Lavard L, Ranlov I, Perrild H, Andersen O, Jacobsen BB. Incidence of juvenile thyrotoxicosis in Denmark, 1982-1988. A nationwide study. Eur J Endocrinol 1994;130:565–8. ISSN 0804–4643
The objective of this study was to ascertain the annual incidence density of thyrotoxicosis in children under the age of 15 years in Denmark in 1982–1988. The design was based on computerized hospital registration of patient admittances in all departments of paediatrics and internal medicine of Denmark (Faroe Islands and Greenland excluded). Fifty-six children (48 girls and 8 boys) had a confirmed diagnosis of thyrotoxicosis, giving a national incidence density of 0.79/100 000 person-years. In children aged 0–4 years the incidence was very low (0.1/100 000), with no sex difference. In boys aged 5–9 years a similar low incidence was found, while in boys aged 10–14 years the incidence increased to 0.48/100 000. In girls aged 5–9 years the incidence increased to 0.96/100 000, reaching a maximum of 3.01 in the 10–14-year-old girls. In children of > 4 years of age a female preponderance of 6.7:1 was significant. It is concluded that thyrotoxicosis is a rare disorder in Danish children under the age of 15 years, and the incidence increases with age. Female preponderance is significant from early childhood.
Lene Lavard, Department of Paediatrics, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark
Purification of high-molecular-weight follicle-stimulating hormone binding inhibitor in porcine follicular fluids
Authors: Furukawa Kenichi , Yamoto Mareo , Kokawa Nobuyoshi , Nakano Ryosuke 
Published: December 2008

Furukawa K, Yamoto M, Kokawa N, Nakano, R. Purification of high-molecular-weight folliclestimulating hormone binding inhibitor in porcine follicular fluids. Eur J Endocrinol 1994;130:625–33. ISSN 0804–4643
We performed the purification of high-molecular-weight follicle-stimulating hormone binding inhibitor (FSHBI) from porcine follicular fluids. The FSHBI activities of high-molecular-weight fractions acquired by ultrafiltration of follicular fluids from small, medium and large follicles with Centriflo CF25 membrane cone were 277.2 ± 24.6, 176.7 ± 3.0 and 141.3 ± 3.6U, respectively. By affinity chromatography of CF25 retentate with a column of Blue Sepharose CL6B, 94.1 ± 5.3% of FSHBI activity was recovered in the unretained fraction. The FSHBI in the unretained fraction was purified by anion-exchange chromatography with a column of Mono Q and gel filtration on Sephacryl S300HR. As a result of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of the final purified fraction, a single silver-stained band was observed at 310 kD under the non-reducing conditions. On the other hand, under the reducing conditions, SDS-PAGE revealed three bands at 178, 101 and 55kD. A double reciprocal plot analysis of this substance showed competitive inhibition in FSH binding. The results of the present study suggest the existence of a 310 kD FSHBI composed of three subunits of 178, 101 and 55 kD in porcine follicular fluids.
K Furukawa, Department of Obstetrics and Gynecology, Wakayama Medical College, Shichibancho 27, Wakayama 640, Japan
Heterogeneity in affinities of serum proteins for thyroxine among patients with non-thyroidal illness as indicated by the serum free thyroxine response to serum dilution
Authors: Wilcox R Bruce , Nelson Jerald C , Tomei Ray T 
Published: December 2008

Wilcox RB, Nelson JC, Tomei RT. Heterogeneity in affinities of serum proteins for thyroxine among patients with non-thyroidal illness as indicated by the serum free thyroxine response to serum dilution. Eur J Endocrinol 1994;131:9–13. ISSN 0804–4643
Some patients with non-thyroidal illness (NTI) have sera with characteristics suggesting decreased functional affinity of thyroxine-binding globulin (TBG) for T4: increased T4 free fraction, decreased total T4 to TBG ratio, and a fall in free T4 with serum dilution greater than theoretical predictions assuming normal affinity. These studies aimed to further characterize this phenomenon. According to the law of mass action binding protein affinity for T4 can be estimated from the response of free T4 to progressive serum dilution. Free T4 responses in 25 normal controls and in 7 congenital TBG deficient controls resembled the predictions from the law of mass action. Among 25 of 38 medical intensive care unit patients, responses were intermediate between normals and TBG deficiency. Responses in the other 13 NTI were consistent with the presence of a dissociable inhibitor. In this subgroup, total T4 was depressed, both free T4 and TSH were elevated, and there was a positive correlation between TSH and free T4 (r2 = 0.41, p < 0.02). Conclusions: (i) decreased affinities of serum proteins for T4 consistent with binding inhibitor(s) are found in some patients with NTI; (ii) there is an association of these severely altered affinities with reversal of the expected free T4–TSH relationship.
R Bruce Wilcox, Department of Biochemistry, Loma Linda University, Loma Linda, CA 92350 USA
Clinical utility of insulin-like growth factor binding protein-3 in the evaluation and treatment of short children with suspected growth hormone deficiency
Authors: Hasegawa Yukihiro , Hasegawa Tomonobu , Aso Taiji , Kotoh Shinobu , Nose Osamu , Ohyama Yoshihide , Araki Kumiko , Tanaka Toshiaki , Saisyo Sumitaka , Yokoya Susumu , Nishi Yoshikazu , Miyamoto Shigeki , Sasaki Nozomu , Kurimoto Fumihiko , Stene Mark , Tsuchiya Yutaka 
Published: December 2008

Hasegawa Y, Hasegawa T, Aso T, Kotoh S, Nose 0, Ohyama Y, Araki K, Tanaka T, Saisyo S, Yokoya S, Nishi Y, Miyamoto S, Sasaki N, Kurimoto F, Stene M, Tsuchiya Y, Clinical utility of insulin-like growth factor binding protein-3 in the evaluation and treatment of short children with suspected growth hormone deficiency. Eur J Endocrinol 1994;131:27–32. ISSN 0804–4643
We have shown previously that serum insulin-like growth factor binding protein-3 (IGFBP-3) levels have good predictive value for complete, but not partial, growth hormone deficiency (GHD). In this study, we compare IGFBP-3 levels in short children previously divided into groups on the basis of their post-stimulation GH levels. Complete GHD (N = 59) included those children with peak poststimulation GH < 5 μg/l. The partial GHD group (N = 49) had post-stimulation GH peaks of > 5 μg/l but < 10 μg/l. The normal children with short stature (N = 103) had post-stimulation GH peaks > 10 μg/l. Partial GHD and normal children with short stature also were divided into either low IGF-I or normal IGF-I subgroups. The clinical sensitivity of IGFBP-3 for complete GHD was 92%, whereas its sensitivity for partial GHD was 39%. For partial GHD, among those with low IGF-I (N = 19) 68% were also low for IGFBP-3, while 80% of those with normal IGF-I (N = 30) were also normal for IGFBP-3. The clinical specificity of IGFBP-3 for normal children with short stature was 69%. For these groups, among those with low IGF-I (N = 22) 73% also were low for IGFBP-3, while 80% of those with normal IGF-I (N = 81) also were normal for IGFBP-3. In addition, we tested whether IGFBP-3 can predict the response to GH treatment in prepubertal children by comparing pretreatment IGFBP-3 with the height gain achieved by 1 year of GH treatment. The incremental growth velocity during treatment correlated significantly with the pretreatment IGFBP-3 sd score (N = 46 r = –0.80, p < 0.005). The baseline IGFBP-3 sd score for all subjects correlated (N = 171, r = 0.51 p < 0.0001) with height. These data suggest that IGFBP-3 may reflect GH secretion status in most children being evaluated for GHD and that a low pretreatment IGFBP-3 sd score predicts improved growth during the first year of GH treatment.
Yukihiro Hasegawa, Division of Endocrinology and Metabolism, Tokyo Metropolitan Kiyose Children's Hospital, 1-3-1 Umezono, Kiyose, Tokyo 204, Japan
Intrinsic secretory characteristics of luteinizing hormone and prolactin episodic release during pubertal development
Authors: Genazzani Alessandro D , Petraglia Felice , Gastaldi Mario , Massolo Fausta , Cellini Monica , Iori Gabriella , Surico Nicola , Genazzani Andrea R 
Published: December 2008

Genazzani AD, Petraglia F, Gastaldi M, Massolo F, Cellini M, Iori G, Surico N, Genazzani AR. Intrinsic secretory characteristics of luteinizing hormone and prolactin episodic release during pubertal development. Eur J Endocrinol 1994;131:80–5. ISSN 0804–4643
The intrinsic characteristics of LH and prolactin (PRL) episodic secretion were evaluated in a group of 18 children (8M and 10F). The children were divided into two groups according to the Tanner stage: Group A (Tanner ≤ 1, N = 7, 3M and 4F, 6–10 years of age) and group B (Tanner 2–3, N = 11, 5M and 6F, 9–11 years of age). A pulsatility study of 4 h, sampling every 10 min, was carried out in all children. LH and PRL plasma levels were assayed by IFMA and RIA respectively. LH and PRL secretory episodes were then identified on plasma determinations using the program detect. Instantaneous secretory rates (ISR) were then computed for both LH and PRL using the specific algorithm within the detect program. Plasma LH levels were different between the two groups of children. Group A children showed undetectable LH plasma levels (below the minimal detectable dose of 0.1 mIU/ml), while group B demonstrated LH plasma levels in the normal range of values for age and sexual development (1.5±0.3 mIU/ml, mean ± sem), LH pulse frequency for group B was 3.2 ±0.4 peaks/4 h. No significant differences in mean plasma PRL levels, pulse frequency and pulse amplitude were observed between the two groups of children. Computation of ISR for LH (group B only) and PRL (both groups) identified the intrinsic episodic characteristics of the two hormones. No significant differences in LH and PRL pulse frequencies were observed when comparing the results estimated on ISR with those estimated on plasma concentrations. No significant changes in PRL pulse amplitude were observed between the two groups. Conversely, a shorter duration of LH and PRL secretory episodes was found. In conclusion, in children PRL secretory bursts from lactotropes lasted the same number of minutes independently of the Tanner stages. Moreover, the LH secretory events were clearly detectable during the daytime only when puberty had already started. The duration of PRL and LH secretory events was similar to adult fertile subjects. These data indicate that the gonadal maturation does not modify LH and PRL secretory events from the pituitary.
Alessandro D Genazzani, Department of Obstetrics and Gynecology, University of Modena, Via del Pozzo 71, 41100 Modena, Italy