bluuebunny/crossref_metadata_2025 huggingface dataset:
Three years of growth hormone treatment in growth hormone-deficient adults: near normalization of body composition and physical performance
Authors: Jørgensen Jens OL , Thuesen Leif , Müller Jørn , Ovesen Per , Skakkebæk Niels E , Christiansen Jens S
Published: December 2008

Jørgensen JOL, Thuesen L, Müller J, Ovesen P, Skakkebæk NE, Christiansen JS. Three years of growth hormone treatment in growth hormone-deficient adults: near normalization of body composition and physical performance. Eur J Endocrinol 1994;130:224–8. ISSN 0804–4643

Growth hormone (GH) replacement therapy in several controlled short-term trials have shown unanimous beneficial effects on body composition and other features. To evaluate more long-term effects we report data from 3 years of uninterrupted GH therapy in 10 GH-deficient adults who had all completed a previous double-blind placebo-controlled study and who also had been studied after 16 months of open GH therapy. No further increase in linear height was observed. The initial increase in thigh muscle volume was maintained after 3 years of GH therapy. A slight increase in body weight and thigh fat volume was recorded. Exercise capacity and isometric muscle strength were increased significantly compared to the initial placebo period. This was associated with stabilized levels of resting heart rate and blood pressure. Glycosylated hemoglobin levels were normal and did not change during the study. A standard oral glucose tolerance test performed at the end of the study revealed no evidence of glucose intolerance. No side-effects were reported. Compared to an age- and sex-matched group of healthy untreated subjects, thigh muscle volume, exercise capacity and isometric muscle strength had become normalized from subnormal levels after 3 years of GH therapy. We conclude that long-term GH replacement therapy in GH-deficient adults is associated with preserved beneficial effects on body composition and physical performance, resulting in a near normalization of several previously abnormal features and adding new merits to this treatment modality.

Jens OL Jørgensen, Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital, DK-8000C, Denmark
No changes of insulin sensitivity in cystic fibrosis patients with different degrees of glucose tolerance: an epidemiological and longitudinal study
Authors: Cucinotta Domenico , De Luca Filippo , Gigante Alfonso , Arrigo Teresa , Benedetto Antonino Di , Tedeschi Antonino , Lombardo Fortunato , Romano Giacomo , Sferlazzas Concetta
Published: December 2008

Cucinotta D, De Luca F, Gigante A, Arrigo T, Di Benedetto A, Tedeschi A, Lombardo F, Romano G, Sferlazzas C. No changes of insulin sensitivity in cystic fibrosis patients with different degrees of glucose tolerance: an epidemiological and longitudinal study. Eur J Endocrinol 1994;130:253–8. ISSN 0804–4643

Plasma glucose and insulin responses to oral glucose and insulin sensitivity by the euglycemic hyperinsulinemic clamp technique were investigated in 30 cystic fibrosis patients with normal fasting blood glucose levels and normal (N = 12), impaired (N = 12) or diabetic (N = 6) glucose tolerance, and in 12 control subjects. In a subgroup of 10 cystic fibrosis patients with non-diabetic glucose tolerance both oral glucose tolerance test and clamp were performed again 48–52 months later. Following oral glucose, glycemic responses were higher in cystic fibrosis patients than in controls, whereas insulin responses were reduced significantly only in the patients with diabetic glucose tolerance. Insulin sensitivity did not differ significantly in the patient subgroups with different degrees of glucose tolerance and in controls. In the 10 patients who underwent a 4-year follow-up, insulin responses to oral glucose decreased significantly, whilst insulin sensitivity did not change substantially. Insulin sensitivity persisted unmodified even in the patients with deteriorating glucose tolerance. No correlations were observed between metabolic data and clinical status of patients. In conclusion, in cystic fibrosis subjects with fasting euglycemia and different degrees of glucose tolerance: (i) insulin sensitivity is not impaired; (ii) eventual changes of glucose tolerance over time are not associated with modifications of insulin sensitivity; (iii) insulin secretion deteriorates over time even in the patients with stable glucose tolerance; (iv) eventual deterioration of both glucose tolerance and insulin secretion is not linked to a worsening of either nutritional or clinical parameters.

F De Luca, Istituto di Clinica Pediatrica, Policlinico Universitario, 98100 Messina, Italy
Estradiol and progesterone production by cultured granulosa cells cryopreserved from in vitro fertilization patients
Authors: Sluss Patrick M , Lee Kan-ei , Mattox John H , Smith Patricia C , Graham Margaret C , Partridge Ann B
Published: December 2008

Sluss PM, Lee K, Mattox JH, Smith PC, Graham MC, Partridge AB. Estradiol and progesterone production by cultured granulosa cells cryopreserved from in vitro fertilization patients. Eur J Endocrinol 1994;130:259–64. ISSN 0804–4643

Gonadotropin-stimulated steroidogenesis was studied in cultured human granulosa-lutein cells obtained from patients undergoing procedures for in vitro fertilization. The impact of cryopreservation on cell function in vitro was studied. Granulosa cells obtained from in vitro fertilization patients were cultured in serum-supplemented medium or cryopreserved at −135°C for 2–22 months. Fresh (unfrozen) cells (105) produced estradiol at a rate of 1320 pmol/l (over 72 h) and progesterone at about 2500 nmol/l. Estradiol production by either fresh or cryopreserved granulosa cells in culture was unaffected by physiological concentrations of follicle-stimulating hormone (7IU/l). Adding testosterone (10−7 mol/l) to the medium increased estradiol secretion approximately sixfold. In contrast, progesterone production was not affected by follicle-stimulating hormone or testosterone. No significant differences were observed in cultures of cryopreserved granulosa cells compared to cultures of unfrozen cells with respect to estradiol secretion, the effects of follicle-stimulating hormone or testosterone on estradiol secretion, or progesterone production. Progesterone production by fresh and cryopreserved cells was stimulated by human chorionic gonadotropin. These data indicate that cryopreservation offers the potential to facilitate prospective studies utilizing large numbers of human granulosa-lutein cells in culture.

Patrick M Sluss, Reproductive Endocrine Unit, Massachusetts General Hospital East, 149 13th Street, Charlestown, MA 02129, USA
Regulation of parathyroid hormone gene expression and peptide secretion in human parathyroid cells
Authors: Liu Jianqi , Kahri Arvi I , Teppo Anna-Maija , Voutilainen Raimo
Published: December 2008

Liu J, Kahri AI, Teppo A-M, Voutilainen R. Regulation of parathyroid hormone gene expression and peptide secretion in human parathyroid cells. Eur J Endocrinol 1994;130:394–401. ISSN 0804–4643

In cell cultures prepared from human parathyroid adenomas, parathyroid hormone (PTH) mRNA expression decreased slowly. During short-term incubations (less than 24), a low calcium concentration (0.5 mmol/l) and protein kinase C activator TPA (12-O-tetradecanoyl phorbol 13-acetate) (160 nmol/l) increased PTH secretion (60%; p <0.05), while a high extracellular calcium concentration (2.5 mmol/l) reduced PTH secretion (60%; p<0.05), The TPA could block the inhibitory effect of a high calcium level on PTH peptide secretion. All these agents had no effect on PTH mRNA accumulation in short-term experiments. In long-term cultures (more than 24 h), a low calcium level increased and a high calcium level reduced both PTH mRNA (85 and 34%; p <0.05) and peptide secretion (140 and 80%; p <0.05), respectively. The TPA reduced PTH mRNA accumulation down to 30% (p<0.05) and PTH secretion down to 14% (p<0.05) in a time- and dose-dependent fashion. The TPA also reversed the stimulatory effect of hypocalcemia on PTH mRNA accumulation and peptide secretion. Protein kinase C inhibitors staurosporine (100 nmol/l) and H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride) (50 μmol/l) had similar effects to TPA on PTH gene expression and peptide secretion in long-term cultures. The results support the hypothesis that extracellular calcium regulates PTH mRNA accumulation and PTH secretion via protein kinase C.

Raimo Voutilainen, Department of Pathology, PO Box 21 (Haartmaninkatu 3), SF-00014 University of Helsinki, Finland
Subterranean mole-rats naturally have an impoverished calciol status, yet synthesize calciol metabolites and calbindins
Authors: Buffenstein Rochelle , Jarvis Jennifer UM , Opperman Lynne A , Cavaleros Meropi , Ross Frederick P , Pettifor John M
Published: December 2008

Buffenstein R, Jarvis JUM, Opperman LA, Cavaleros M, Ross FP, Pettifor JM. Subterranean mole-rats naturally have an impoverished calciol status, yet synthesize calciol metabolites and calbindins. Eur J Endocrinol 1994;130:402–9. ISSN 0804–4643

Mole-rats (Family Bathyergidae) have no obvious source of calciol. They live in an environment devoid of sunlight and consume a herbivorous diet. Calciol status, metabolism and expression were examined in six species of Bathyergids. Serum levels of calcidiol in all species were < 5μg/l and those of calcitriol were low (18.0 ± 11.0 (sd) ng/l, N = 57) when compared to other rodents. Within 72 h of injecting animals with tritium-labelled calciol, most of the labelled prohormone had been metabolized to more polar metabolites. Three times more tritium-labelled calcitriol (19.3 ± 2.9%) was present than (24R)-hydroxycalcidiol (6.2 ± 10%). The natural absence of detectable circulating concentrations of calcidiol and the threefold greater amount of calcitriol to (24R)-hydroxycalcidiol produced indicate that calciol naturally is in short supply. Calciol-dependent calbindins were absent in the duodenum. Calbindin-D28k was present in the Purkinje cells of the cerebellum and in some collecting ducts and proximal and distal convoluted tubules of the kidney. Calbindin-D9k also was present but was localized uniquely in the juxtaglomerular cells of the five southern African species. These data confirm that Bathyergid mole-rats naturally have an impoverished calciol status. Despite the presence of calbindins in renal tissues, the functional importance of this hormone in calbindin synthesis and other normal mole-rat physiology is not known.

R Buffenstein, Department of Physiology, University of the Witwatersrand, Medical School, 7 York Road, Parktown 2193, South Africa
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
Functional relevance of luteinizing hormone receptor in mouse uterus
Authors: Mukherjee D , Manna PR , Bhattacharya S
Published: December 2008

Mukherjee D, Manna PR, Bhattacharya S. Functional relevance of luteinizing hormone receptor in mouse uterus. Eur J Endocrinol 1994;131:103–8. ISSN 0804–4643

The presence of high-affinity luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptors has been reported in porcine, rabbit, rat and human uteri. We have demonstrated binding of [125I]LH to mouse uterus, which was saturable. Scatchard plot analysis indicated Kd to be 1.37 × 10−10 mol/l and the maximum binding capacity to be 5.24 nmol/kg protein. Attempts have been made to observe the functional relevance of gonadotropin receptor in the mouse uterus. The size and weight of the uterus remarkably decreased as a result of ovariectomy; administration of LH to ovariectomized (OVX) mice significantly increased the uterine weight in comparison to the OVX control (p < 0.01), indicating a direct effect of LH on the uterus. There was a two-fold decrease of uterine ascorbic acid content in LH-treated OVX mice as compared to the intact control. The gain in uterine weight of OVX mice by LH was due to the increase in uterine protein synthesis. The stimulatory effect of LH on OVX mice uterus appears to be mediated via steroid hormones because it significantly augmented uterine mitochondrial steroidogenesis. Since 17β-estradiol (E2) is known to stimulate uterine protein synthesis, the circulatory level of E2 was determined in intact, OVX and OVX + LHtreated mice. A fall in the circulatory level of E2 occurred in OVX mice as compared to the control, while treatment of LH for 7 days (three injections) significantly elevated E2 levels in OVX mice (p < 0.001). This higher level of E2 in OVX mice remains unaltered on adrenalectomy, indicating that adrenals are not the source for increased E2 levels. Data therefore imply that LH can stimulate uterine E2 formation. Results from an in vitro incubation of uterine tissue from intact, OVX and OVX + LHtreated mice showed that ovariectomy caused a sharp drop of E2, while treatment with LH significantly increased E2 release and the uterine contents. Hence, it may be suggested that LH has a direct effect on the uterus of OVX mice: by occupying a high-affinity binding site it stimulates steroidogenesis, resulting in higher E2 formation, which, in turn, dramatically increases uterine weight by stimulating protein synthesis.

S Bhattacharya, School of Life Science, Department of Zoology, Visva-Bharati University, Santiniketan 731 235, West Bengal, India
Luteinizing hormone secretory pattern before and after removal of Leydig cell tumor of the testis
Authors: Caron Philippe J , Bennet Antoine P , Plantavid Monique M , Louvet Jean-Pierre
Published: December 2008

Caron PJ, Bennet AP, Plantavid MM, Louvet J-P. Luteinizing hormone secretory pattern before and after removal of Leydig cell tumor of the testis. Eur J Endocrinol 1994;131:156–9. ISSN 0804–4643

We studied the luteinizing hormone (LH) secretory pattern in three patients, aged 30, 23 and 43 years, with gynecomastia due to Leydig cell tumor of the testis, before and 6 months after unilateral orchidectomy. The results were compared to those of 11 normal fertile controls aged 20–35 years. Blood sampling was done at 20-min intervals from 22.00 h to 10.00 h. The LH data were analyzed with the Cluster analysis algorithm with "optimal parameters for LH male data" to determine the pulse interval and pulse amplitude. The Expfit program was applied to LH pulses to calculate the apparent half-life of immunoreactive LH. Before surgery, when compared to controls, the patients had a low to normal testosterone/estradiol ratio (0.053, 0.110, 0.046 vs 0.148 ± 0.038) and mean LH levels (1.96, 3.7, 2.55 vs 4.0 ± 1.9 IU/l), decreased pulse amplitude (2.65, 3.01, 2.21 vs 3.31 ± 1.41 IU/l) and reduced apparent half-life of LH (74, 69, 78 vs 97 ± 16 min). After removal of the Leydig cell tumor, the testosterone/estradiol ratio returned to the normal range (0.141, 0.177, 0.093) while an increase in mean LH levels (5.75, 7.90, 4.88 IU/l), LH pulse amplitude (3.07, 6.05, 2.86 IU/l) and apparent half-life of LH (138, 106, 104 min) was observed in all three patients. Our data indicate that endogenous hyperestrogenism in patients with Leydig cell tumor of the testis results in an inhibition of LH secretion, and suggests that such inhibition could result from a reduction in pulse amplitude and apparent half-life.

Philippe Caron, Service d'Endocrinologie et Maladies métaboliques, CHU Rangueil, 1 Avenue J Poulhes, 31054 Toulouse Cedex, France
Diurnal rhythm of testosterone induced by human chorionic gonadotrophin (hCG) therapy in isolated hypogonadotrophic hypogonadism: a comparison between subcutaneous and intramuscular hCG administration
Authors: Jones T Hugh , Darne Joe F , McGarrigle Hugh HG
Published: December 2008

Jones TH, Darne JF, McGarrigle HHG. Diurnal rhythm of testosterone induced by human chorionic gonadotrophin (hCG) therapy in isolated hypogonadotrophic hypogonadism: a comparison between subcutaneous and intramuscular hCG administration. Eur J Endocrinol 1994;131:173–8. ISSN 0804–4643

When human chorionic gonadotrophin (hCG) is used to stimulate testosterone synthesis and release in males with hypogonadotrophic hypogonadism, it is administered two or three times weekly by intramuscular injection. We have compared the pharmacokinetics of a twice weekly standard dose of hCG (5000 U) given for the first week by intramuscular injection and in the second week by self-administered subcutaneous injection. The patients studied had Kallmann's syndrome, isolated idiopathic hypogonadotrophic hypogonadism or post-traumatic isolated hypogonadotrophic hypogonadism. Salivary testosterone was collected twice daily at 08.00 h and 20.00 h, and serum testosterone was collected after 0, 24 h, 72 h, 120 h and 168 h each week. The cumulated serum and salivary testosterone levels were comparable on both intramuscular and subcutaneous hCG. In normal males there is diurnal variation in testosterone, with peak serum levels in the morning falling to a nadir in the evening. The exact nature and controlling factors of this circadian rhythm have not been established. In four of the subjects, the twice weekly hCG injections, either subcutaneous or intramuscular, produced a regular testosterone diurnal rhythm. The other four patients had fluctuations in testosterone but with no strict diurnal pattern. This study provides evidence that the luteinizing hormone-like action of hCG is necessary to prime the circadian rhythm but only a single bolus of hCG is sufficient to induce the rhythm in the absence of endogenous gonadotrophin production. In conclusion, self-administered subcutaneous hCG is safe and produces comparable levels of serum and salivary testosterone to that administered by the intramuscular route. Moreover, it was very well accepted by the patients and was preferred to conventional treatments. Human hCG in some patients with hypogonadotrophic hypogonadism produces normal physiological changes in daily testosterone levels.

TH Jones, University Department of Medicine, Clinical Sciences Centre, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK
A carnivore species (Canis familiaris) expresses circadian melatonin rhythm in the peripheral blood and melatonin receptors in the brain
Authors: Stankov Bojidar , Møller Morten , Lucini Valeria , Capsoni Simona , Fraschini Franco
Published: December 2008

Stankov B, Møller, M, Lucini V, Capsoni S, Fraschini F. A carnivore species (Canis familiaris) expresses circadian melatonin rhythm in the peripheral blood and melatonin receptors in the brain. Eur J Endocrinol 1994;131:191–200. ISSN 0804–4643

Dogs kept under controlled photoperiodic conditions of 12 h light and 12 h dark expressed a clear diurnal melatonin rhythm in the peripheral blood, with a swift peak restricted to the late part of the scotophase. The highest density of high-affinity, G-protein-linked 2-[125I]iodomelatonin binding sites was found in the pars tuberalis of the pituitary gland. Binding sites were found also in the pars distalis, and light microscopy/high-resolution autoradiography showed that binding was located exclusively over the chromophobe and basophilic cells forming the adenopituitary zona tuberalis, well developed in this species, and extending into the gland as a continuation of pars tuberalis. Cords of basophilic cells located in the pars distalis proper also expressed high receptor density. The eosinophils in the adenohypophysis and the neural lobe were devoid of binding. Heavily labeled were the external laminar and the mitral cell layers of the olfactory bulbs, but no binding was detected in the filae nervi olfactorii or tractus olfactorius. The hypothalamic suprachiasmatic nuclei were discernible clearly. Quantitative autoradiography inhibition experiments revealed that the apparent melatonin inhibitory constant (ic50) in all those areas was around 0.1 nmol/l, which is a physiologically appropriate value considering the peripheral blood melatonin levels. Co-incubation with guanosine 5′-O-(3-thiotriphosphate) (GTPΓS) led to a consequential decrease in the binding density. The specific binding observed in other areas (hippocampus, frontal, parietal, occipital cortex and cerebellum) was rather weak, diffuse and could not be attributed to a particular layer; the apparent ic50 for melatonin was about 1 μmol/l, and co-incubation with GTPΓS did not modify the binding density. Collectively, these data show that the dog posesses all the prerequisites for an efficient network adapted to photoperiodic time measurements. A circadian melatonin signal in the peripheral blood and an apparently functional readout receptor system located in key positions within the brain are both present in this species.

Bojidar Stankov, Chair of Chemotherapy, Department of Pharmacology, University of Milan, 32 Via Vanvitelli, 20129 Milano, Italy
Regulation of quail oviduct phospholipase A2 activity by estradiol
Authors: Fayard JM , Chanal S , Felouati B , Macovschi O , Lagarde M , Pageaux JF , Laugier C
Published: December 2008

Fayard JM, Chanal S, Felouati B, Macovschi O, Lagarde M, Pageaux JF, Laugier C. Regulation of quail oviduct phospholipase A2 activity by estradiol. Eur J Endocrinol 1994;131:205–12. ISSN 0804–4643

The phospholipase A2 (PLA2) activity was measured in the oviduct of immature and estradiol benzoate (EB)-treated quails. The pH profiles demonstrate the presence of two PLA2 isoforms in the avian oviduct: a neutral isoform, optimally active at pH 7–7.5 and calcium independent, responsible for most of the hydrolytic activity in the immature oviduct and poorly stimulated by estradiol; and an alkaline isoform, optimally active at pH 8–9.5 and calcium dependent, with little activity in the immature tissue but markedly stimulated by EB. After EB injection, PLA2 activation occurs at first during the prereplicative period of oviduct cells (+172% at 6 h), it is dose dependent from 0.01 to 1 mg/kg EB and can be prevented by cycloheximide together with ornithine decarboxylase activation. Moreover, estradiol was inactive on cell-free extracts of immature oviducts. These results suggest that EB increases PLA2 activity through gene activation and de novo protein synthesis. The correlation between the early stimulation of PLA2 activity and the proliferation of oviduct cells is discussed.

JM Fayard, INSERM U.352, Laboratoire de Physiologie–Pharmacodynamie, INSA 406, 69621 Villeurbanne Cedex, France
McCune–Albright syndrome and acromegaly: clinical studies and responses to treatment in five cases
Authors: Chanson Philippe , Dib Anne , Visot André , Derome Patrick J
Published: December 2008

Chanson P, Dib A, Visot A, Derome PJ. McCune–Albright syndrome and acromegaly: clinical studies and responses to treatment in five cases. Eur J Endocrinol 1994;131:229–34. ISSN 0804–4643

We report here five new patients with McCune–Albright syndrome and acromegaly. In the five patients studied (three males and two females aged 19–42 years), acromegaly began before the age of 20 years and was recognized after the diagnosis of fibrous dysplasia, which was polyostotic in three cases and monostotic in two. Bone fibrous dysplasia always involved the base of the skull and in four patients prevented surgical removal of the pituitary adenoma, which was visualized easily by magnetic resonance imaging. Serum growth hormone (GH) levels ranged between 20 and 48 μg/l and were not suppressed by an oral glucose load. Thyrotropin-releasing hormone administration produced a paradoxical increase in serum GH levels in all the patients. Four of the five patients had hyperprolactinemia (43–670 μg/l). In the sole patient who could be operated on, a typical adenoma with positive immunostaining for GH was incompletely removed and postoperative radiation therapy failed to cure the acromegaly. In two patients, medical therapy with bromocriptine and/or octreotide was partially or totally ineffective whatever the dose (up to 1.5 mg per day) and duration (2–4 years) of octreotide treatment.

Philippe Chanson, Service d'Endocrinologie et Maladies de la Reproduction, Hôpital Bicêtre, F94275 Le Kremlin-Bicêtre, France
Bone resorption in healthy and osteoporotic postmenopausal women: comparison markers for serum carboxy-terminal telopeptide of type I collagen and urinary pyridinium cross-links
Authors: Välimäki Matti J , Tähtelä Riitta , Jones James D , Peterson James M , Riggs B Lawrence
Published: December 2008

Välimäki MJ, Tähtelä R, Jones JD, Peterson JM, Riggs BL. Bone resorption in healthy and osteoporotic postmenopausal women: comparison markers for serum carboxy-terminal telopeptide of type I collagen and urinary pyridinium cross-links. Eur J Endocrinol 1994;131:258–62. ISSN 0804–4643

We compared two highly specific markers for bone resorption–pyridinium cross-links (pyridinoline (PYR) and deoxypyridinoline (DPR)) in urine and carboxy-terminal telopeptide of type I collagen (ICTP) in serum – in 63 healthy postmenopausal women and 63 women with osteoporosis characterized by more bone resorption than bone formation. The ICTP, PYR and DPR levels were all higher, by 24% (p = 0.001), 16% (p = 0.05) and 25% (p = 0.004), respectively, in the osteoporotic women. For the merged groups, there were significant correlations between serum ICTP concentration and urinary PYR (r = 0.667, p < 0.0001) and DPR (r = 0.452, p < 0.0001) excretion; for the osteoporotic and normal women separately, the r values were 0.73 (p < 0.01) and 0.45 (p < 0.01) for PYR and 0.51 (p < 0.01) and 0.22 (p = 0.08) for DPR versus ICTP respectively. Weak correlations in linear regression between ICTP and various indices of bone formation (osteocalcin, bone-specific alkaline phosphatase and carboxy-terminal propeptide of type I procollagen) disappeared when the correlation between ICTP and pyridinolines was accounted for by calculation of partial correlation coefficients in multiple regression analysis. Serum ICTP concentration appears to discriminate between groups of normal and osteoporotic women as well as urinary pyridinium cross-links, which is thus far the most sensitive method for assessing bone resorption.

Matti Välimäki, Third Department of Medicine, Helsinki University Central Hospital, SF-00290 Helsinki, Finland