bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of testicular anti-Müllerian hormone secretion
Authors: Rey Rodolfo , Josso Nathalie 
Published: December 2008

Rey R, Josso N. Regulation of testicular anti-Müllerian hormone secretion. Eur J Endocrinol 1996; 135:144–52. ISSN 0804–4643
Anti-Müllerian hormone (AMH) is a glycoprotein secreted by Sertoli cells from the time of testicular differentiation and is responsible for the regression of Müllerian ducts in the male fetus. The chronology of AMH expression is very important because Müllerian ducts lose their responsiveness a few days after AMH secretion begins, which suggests that the AMH gene is under precise transcriptional control. Steroidogenic factor 1 (SF-1) is the only transcriptional regulator with demonstrated action on AMH expression. Although necessary for AMH expression, SF-1 alone is not sufficient to induce AMH transcription. SRY expression is turned on in Sertoli cells just before AMH expression is initiated, but the effective implication of SRY in AMH regulation remains unclear. During puberty, AMH expression is regulated negatively by androgens and declines dramatically in seminiferous tubules with meiotic development. Low serum AMH levels are observed in both central and gonadotropin-independent precocious puberty, which suggests that gonadotropins do not downregulate AMH at puberty. Serum AMH returns to normal infantile values 3–6 months after treatment. The absence of androgen response elements on the AMH promoter and the slow response to androgen withdrawal suggest that androgen regulation of AMH secretion is indirect. In patients with defects of androgen production or action, serum AMH reaches abnormally high levels in the neonatal and pubertal periods, which suggests a possible stimulatory role for gonadotropins that could be observed only in the absence of suppressive effects of androgens.
Rodolfo Rey, INSERM U.293, Ecole Normale Supérieure, 1 rue Maurice Arnoux, 92120 Montrouge, France
Regional comparison of prolactin gene expression in the human decidualized endometrium in early and term pregnancy
Authors: Tanaka Soichiro , Koibuchi Noriyuki , Ohtake Hideki , Ohkawa Hiroshi , Kawatsu Takeshi , Tadokoro Nozomu , Kumasaka Takahiro , Inaba Noriyuki , Yamaoka Sadao 
Published: December 2008

Tanaka S, Koibuchi N, Ohtake H, Ohkawa H, Kawatsu T, Tadokoro N, Kumasaka T, Inaba N, Yamaoka S. Regional comparison of prolactin gene expression in the human decidualized endometrium in early and term pregnancy. Eur J Endocrinol 1996;135:177–83. ISSN 0804–4643
Prolactin (PRL) is known to be expressed in the decidualized human endometrium and secreted into amniotic fluid. Although the site of synthesis of endometrial PRL is known to be the decidual cells, the difference in PRL gene expression within each area of decidua, i.e. decidua basalis, decidua parietalis and decidua capsularis, during pregnancy is not clear. We have applied an in situ hybridization histochemistry technique using a radiolabeled RNA probe to compare the difference in expression of PRL gene within each area of the decidualized endometrium. Specific hybridization signals were distributed over the decidual cells in early and term pregnancy. More intense hybridization signals were always detected in the tissues of early pregnancy than in those of term pregnancy. In the decidua capsularis of early pregnancy, labeled cells were concentrated close to the amniotic cavity, whereas cells were concentrated close to the maternal surface of the fetal membrane in term pregnancy. In the decidua parietalis, almost all decidual cells were labeled, but no specific labeling was seen in the endometrial glands or capillary endothelium in both groups. In the decidua basalis, most decidual cells showed hybridization signals whereas no hybridization signal was seen over the trophoblast cells. These results show that there are regional and periodic differences in PRL gene expression in the decidual cells during pregnancy.
Noriyuki Koibuchi, Department of Physiology, Dokkyo University School of Medicine, Mibu, Tochigi 321-02, Japan
Decreasing melatonin and 6-hydroxymelatonin sulfate excretion with advancing gestational age in preterm and term newborn male infants
Authors: Commentz JC , Henke A , Dammann O , Hellwege HH , Willig RP 
Published: December 2008

Commentz JC, Henke A, Dammann O. Hellwege HH, Willig RP. Decreasing melatonin and 6-hydroxymelatonin sulfate excretion with advancing gestational age in preterm and term newborn male infants. Eur J Endocrinol 1996;135:184–7. ISSN 0804–4643
We investigated the ontogeny of melatonin synthesis during fetal maturation by measuring the melatonin (MLT) and 6-hydroxymelatonin sulfate (MLTS) excretion in the urine of male infants aged 2–7 days and gestational age 26–42 weeks. We found a negative correlation between advancing gestational age and the MLT and MLTS excretion expressed as total 24-h amount, ratio of 24-h amount to creatinine and ratio of 24-h amount to body surface area. The ratio of MLT to MLTS was found to be about ten times higher in the study group than in prepubertal children, which might reflect the immaturity of hepatic sulfation capacities. The total amount of excreted MLT and MLTS was only one-tenth the prepubertal values. No day/night differences in MLT and MLTS excretion could be detected. We conclude that the fetal pineal gland is capable of a limited melatonin synthesis from the 26th week of gestation onwards, with decreasing values reaching its nadir around term. This indicates that the amount of fetal MLT excretion is not determined by synthesizing capacities of the pineal gland but by the development of neural connections to the pineal gland.
JC Commentz, Department of Pediatrics UKE, University of Hamburg, Martinistrasse 52, D-20246, Hamburg, Germany
Decrease in melatonin precedes follicle-stimulating hormone increase during perimenopause
Authors: Vakkuri Olli , Kivelä Aarre , Leppäluoto Juhani , Valtonen Maija , Kauppila Antti 
Published: December 2008

Vakkuri O, Kivelä A, Leppäluoto J, Valtonen M, Kauppila A. Decrease in melatonin precedes folliclestimulating hormone increase during perimenopause. Eur J Endocrinol 1996;135:188–92. ISSN 0804–4643
Melatonin, the hormone of the pineal gland, which in animal studies has been found to inhibit aging processes, is secreted in smaller amounts towards senescence. Menopause, an aging process in women, is known to be associated with typical changes in gonadotropin and sex steroid secretion. Our main objective was to study the possible role of melatonin in the hormonal regulation of menopause. This study focused on detailed changes in melatonin and follicle-stimulating hormone (FSH) secretion cross-sectionally in pre- to postmenopausal females. Special attention was paid to females aged around 50 years, which is the mean menopausal age. Seventy-seven healthy female volunteers aged 30–75 years were the subjects of this study. Melatonin was measured radioimmunologically from nocturnal urine collected between 20.00 and 08.00 h, and FSH and melatonin from blood samples taken at 09.00 h. Nocturnal urinary excretion of melatonin was found to decline significantly from premenopause to postmenopause. The youngest premenopausal women (age group 30–39 years) excreted the highest amounts of melatonin (21.1 ± 2.2 pmol/h, mean±sem, N = 17). In the age group 40–44 years the excretion declined by 41% (p < 0.05). The second significant decline (35%, p < 0.05) took place between the age groups 50–54 years and 55–59 years. A declining trend as a function of age was also seen in morning serum melatonin. Serum FSH rose sharply to high levels before the age of 50 (p < 0.01) and remained at a high level thereafter. Urinary melatonin correlated negatively with serum FSH (r = −0.32. p < 0.05). In conclusion, the inverse changes in melatonin and FSH secretion during the perimenopausal years, with the sharpest decline in nocturnal excretion of melatonin far before menopause, suggest that melatonin may be permissively linked to the initiation of menopause.
O Vakkuri. Department of Physiology. University of Oulu, Kajaanintie 52 A, 90220 Oulu, Finland
Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone
Authors: Saggese Giuseppe , Cesaretti Graziano , Franchi Giulia , Startari Luisa 
Published: December 2008

Saggese G, Cesaretti G, Franchi G, Startari L. Testosterone-induced increase of insulin-like growth factor I levels depends upon normal levels of growth hormone. Eur J Endocrinol 1996;135:211–5. ISSN 0804–4643
Pubertal development is associated with a rise in plasma insulin-like growth factor I (IGF-I) levels that is related both to the increase in sex steroids and/or to the sex steroid-induced augmentation in endogenous growth hormone (GH) secretion. In order to investigate the relationship between IGF-I. GH and testosterone, we examined 42 male subjects with various clinical conditions (classical GH deficiency (CGHD, N = 5), non-classical GH deficiency (NCGHD, N = 7), short idiopathic stature (N = 6), nutritional obesity (N = 8), GH-treated CGHD (N = 4), GH-treated NCGHD (N = 5) and normal stature (N = 7)) in which, for evaluation of hypogonadism (i.e. the absence of one or both testes from the scrotal sac), human chorionic gonadotropin (hCG) tests were performed. We measured IGF-I, total and free testosterone and dehydroepiandrosterone sulfate (DHEAS) by radioimmunoassays before and 48 and 96 h after the start of the test. The values of IGF-I were lower (0.001 < p < 0.005) in CGHD and NCGHD than in the other groups. In comparison to basal levels, IGF-I values increased (0.005 < p < 0.05) both 48 and 96 h after the start of the hCG test in short idiopathic and normal stature children and in GH-treated subjects with NCGHD, but only 96 h in subjects with untreated NCGHD and GH-treated CGHD. No difference was demonstrated in basal values of total testosterone among any of the groups, while basal free testosterone levels were higher (0.001 < p < 0.05) in GH-treated subjects with NCGHD than in all the other groups except nutritional obesity; furthermore, free testosterone was higher (p < 0.05) in nutritional obesity than in CGHD. The values of total and free testosterone obtained both 48 and 96 h after the start of the hCG test were higher (0.001 < p < 0.05) than basal values in all groups. The DHEAS values did not show any significant change during the hCG test. Basal values were higher (0.01 <p < 0.05) in nutritional obesity than in the other groups. Considering all groups, chonological age, bone age and bone age/chronological age ratio were correlated with basal free testosterone, IGF-I and DHEAS levels (0.001 < p < 0.05), while basal free testosterone and IGF-I values were correlated with DHEAS levels (p < 0.005 and <0.01, respectively). In conclusion, our study during the hCG test in boys with various clinical conditions demonstrated an increase in IGF-I concentrations only in those boys with sufficient GH secretion or GH replacement therapy. These findings indicate that both sex steroids and GH are necessary to allow for the pubertal increase in IGF-I levels.
Giuseppe Saggese, Endocrine Unit, Department of Pediatrics, University of Pisa, Via Rome 67, 56125 Pisa, Italy
Thyroxine binding to transthyretin (TTR) variants—two variants (TTR Pro 55 and TTR Met 111) with a particularly low binding affinity
Authors: Almeida Maria Rosário , Saraiva Maria João 
Published: December 2008

Almeida MR, Saraiva MJ. Thyroxine binding to transthyretin (TTR) variants—two variants (TTR Pro 55 and TTR Met 111) with a particularly low binding affinity. Eur J Endocrinol 1996;135:226–30. ISSN 0804–4643
Thyroxine (T4) binding is a well-characterized function of transthyretin (TTR) and has been used to assess structural alterations of TTR variants. Most TTR variants deposit as amyloid fibrils originating different forms of hereditary amyloidosis. It has been hypothesized that amino acid substitutions in the TTR variants induce structural alterations that may be responsible for the amyloidogenicity of the mutant proteins. To test for structural alterations in TTR, we studied T4 binding to TTR variants both in whole serum and in isolated form obtained from heterozygotic carriers of amyloidogenic and non-amyloidogenic variants and compared the binding with the corresponding homozygotic recombinant variants. The results obtained indicated a normal T4 binding affinity for heterozygotic TTR Ala 49, TTR Leu 68, TTR Ala 71 and TTR Arg 102. Concerning TTR Pro 55 and TTR Met 111, we found a consistent decrease in binding affinity. These results were more pronounced for the equivalent recombinant proteins. Recombinant TTR Pro 55 did not show specific binding to T4 and recombinant TTR Met 111 presented very low binding affinity. Neither TTR Pro 55 nor TTR Met 111 are localized in the T4 binding channel, thus structural alterations induced by these mutations should be transmitted to the binding channel interfering with T4 binding. The results now reported, together with ongoing structural data by X-ray analyses on mutants Pro 55 and Met 111 and future binding studies with other ligands, will contribute to the elucidation of the structure and function of TTR, particularly in thyroid hormone metabolism.
Maria João Saraiva, Centro de Estudos de Paramiloidose, Hospital de Santo António, 4050 Porto, Portugal
Technical and clinical validation of a new immunoradiometric assay for human osteocalcin
Authors: Dumon JC , Wantier H , Mathieu F , Mantia M , Body JJ 
Published: December 2008

Dumon JC, Wantier H, Mathieu F, Mantia M, Body JJ, Technical and clinical validation of a new immunoradiometric assay for human osteocalcin. Eur J Endocrinol 1996;135:231–7. ISSN 0804–4643
The measurement of circulating osteocalcin or bone GLA protein (BGP) constitutes a well established and non-invasive means for evaluating preferentially the bone formation rate, but most available commercial assays suffer from several technical constraints, notably a rapid degradation of BGP at room temperature or after thawing and the inability to measure subnormal values. We evaluated, from a technical and a clinical viewpoint, a newly available two-site sandwich immunoradiometric assay (IRMA) using standards of human origin and two different monoclonal antibodies. The theoretical and functional assay detection limit was 0.3 ng/ml. Concentrations of BGP progressively decreased when the serum was left at 4°C or at room temperature (mean apparent loss of 15% after 24 h). Two cycles of freezing–thawing only slightly reduced the BGP concentrations. The mean (± sd) BGP concentration was 19.6 ± 7.9 ng/ml in healthy subjects (NI, N = 61); the normal range was 8.1–35.6 ng/ml. There was a marked difference between pre- and postmenopausal women: 15.1 ±4.4 vs 22.3 ± 8.4 ng/ml, respectively (p<0.05). The mean BGP concentration in patients with tumor-induced hypercalcemia (N = 29) was not significantly different from NI, but nine patients (31%) had subnormal levels and five (17%) had elevated BGP levels. Concentrations of BGP were significantly increased in patients with hyperparathyroidism (N = 14) (45.1 ± 21.0 ng/ml) and significantly lower than NI in patients with hypoparathyroidism (N = 18) (7.3 ± 4.6 ng/ml). Concentrations of BGP were also measured by a classical radioimmunoassay using bovine standards and tracer; the correlations between both sets of measurements were significant in all groups, except in patients with hypoparathyroidism. In summary, this newly available IRMA for measuring circulating human BGP appears to be quite sensitive, reproducible and robust. It should be especially useful for investigating clinical conditions characterized by a low bone formation rate.
JJ Body, Institut Jules Bordet, Rue Héger-Bordet 1, 1000 Brussels, Belgium
11β-Hydroxysteroid dehydrogenase deficit: a rare cause of arterial hypertension. Diagnosis and therapeutic approach in two young brothers
Authors: Gourmelen Micheline , Saint-Jacques Irène , Morineau Gilles , Soliman Hany , Julien René , Fiet Jean 
Published: December 2008

Gourmelen M. Saint-Jacques I, Morineau G. Soliman H, Julien R, Fiet J. 11β-Hydroxysteroid dehydrogenase deficit: a rare cause of arterial hypertension. Diagnosis and therapeutic approach in two young brothers. Eur J Endocrinol 1996;135:238–44. ISSN 0804–4643
We report the clinical history and results of endocrine investigations in two brothers born to consanguineous parents, who presented with hypokalemia and arterial hypertension when they were aged 2 and 6 years. The hormonal serum assay results, including extremely low values for aldosterone and plasma renin activity, favored the existence of apparent mineralocorticoid excess. A diagnosis of 11β-hydroxysteroid dehydrogenase (11β-HSD) deficiency was made, based on assays of the hydrogenated urinary metabolites of cortisol and cortisone, as well as of corticosterone and dehydrocorticosterone. Indeed we found a very low rate of urinary elimination of cortisone metabolites: tetrahydrogenated cortisone was reduced to between 0.10 and 30 μmol/24 h, which is 15–100 times lower than the normal rate; hexahydrogenated cortolones a and β were found to be 7-to 20-fold lower than normal levels; and the 11-keto-17-ketosteroid derivatives of cortisone were also reduced. Urinary elimination of the cortisol-reduced metabolites 5β- and 5α-tetrahydrogenated cortisol were slightly reduced or normal. These results argue in favor of a deficit in the enzyme 11β-HSD, which oxidizes cortisol into cortisone. A moderate defect in the conversion of cortisol into 5β-THF compared to normal conversion into 5α-THF was also found. With respect to corticosterone metabolism, we demonstrated the presence of a defect in the oxidation of that steroid into dehydrocorticosterone, also due to the deficit in 11β-HSD. Arterial hypertension and hypokalemia were corrected by treatment with dexamethasone, concomitantly with correction of the low aldosterone and plasma renin activity levels. On the other hand, during this treatment, urinary concentrations of the metabolites of cortisol. cortisone and corticosterone were only moderately affected.
Jean Fiet, Laboratoire de Biologie Hormonale, Hôpital Saint-Louis, I Avenue Claude Vellefaux, 75475 Paris Cedex 10, France
Hyponatraemia secondary to cerebral salt wasting syndrome following routine pituitary surgery
Authors: Atkin Stephen L , Coady Anne Marie , White Michael C , Mathew Bruce 
Published: December 2008

Atkin SL, Coady AM. White MC, Mathew B. Hyponatraemia secondary to cerebral salt wasting syndrome following routine pituitary surgery. Eur J Endocrinol 1996;135:245–7. ISSN 0804–4643
A female aged 53 years was found to have a suprasellar lesion, which was shown to be a Rathke's cyst after removal by transsphenoidal surgery. She presented 16 days postoperatively, and following two grand mal seizures was found to be profoundly hyponatraemic (sodium 101 mmol/l). She was initially thought to have the syndrome of inappropriate antidiuretic hormone and was treated accordingly, but central venous pressure measurement revealed the hypovolaemia of cerebral salt wasting syndrome. The patient subsequently developed severe neurological sequelae after the correction of her hyponatraemia, following the development of extrapontine myelinolysis. Cerebral salt wasting syndrome is a rare cause of hyponatraemia following pituitary transsphenoidal surgery, which may mimic the syndrome of inappropriate antidiuretic hormone secretion. This case emphasizes the poor prognosis that may result from the rapid correction of profound hyponatraemia.
SL Atkin, Michael White Centre for Diabetes and Endocrinology, Royal Hull Hospitals, 220-236 Anlaby Road, Hull HU3 2RW, UK
Hyperprolactinaemia is associated with a higher prevalence of pituitary–adrenal dysfunction in non-functioning pituitary macroadenoma
Authors: Tjeerdsma Geert , Sluiter Wim J , Hew Joffre M , Molenaar Willemina M , de Lange Willem E , Dullaart Robin PF 
Published: December 2008

Tjeerdsma G, Sluiter WJ, Hew JM, Molenaar WM, de Lange WE, Dullaart RPF. Hyperprolactinaemia is associated with a higher prevalence of pituitary—adrenal dysfunction in non-functioning pituitary macroadenoma. Eur J Endocrinol 1996;135:299—308. ISSN 0804–4643
In non-functioning pituitary macroadenoma (NFMA), hyperprolactinaemia (hyperPRL) is considered to be a sign of hypothalamic—pituitary dysregulation, but it is unknown whether hyperPRL is associated with an increased frequency of pituitary hormone deficiencies. Forty consecutive patients with histology-proven NFMA were studied and hyperPRL was defined as serum prolactin (PRL) >200 mIU/l in men and >600 mIU/l in women. The pituitary—adrenal axis was evaluated by measurement of urinary free cortisol (N = 38), peak cortisol to insulin-induced hypoglycaemia (IIH, N = 36) and to human corticotrophin-releasing hormone (hCRF, N = 40) and by urinary tetrahydro11-deoxycortisol (H4S, N = 39), plasma androstenedione increment (N = 39) and serum 11-deoxycortisol (N = 1) after metyrapone. Central hypothyroidism, gonadotrophin deficiency and growth hormone (GH) reserve were also assessed. Twenty patients had hyperPRL (serum PRL 331 (2231120)mIU/l (median, range) in men and 932 (660–3927)mIU/l in women); urinary free cortisol excretion (p < 0.03) and peak serum cortisol in response to IIH (p < 0.02) were lower in hyperPRL than in normoPRL patients; peak serum cortisol after hCRF was not different between groups but occurred later in hyperPRL patients (at 60 vs 30 min, p < 0.03); urinary H4S excretion and androstenedione response after metyrapone were lower in hyperPRL than in normoPRL patients (p < 0.05 for both); 60% of hyperPRL patients and 15% of normoPRL patients had an abnormal H4S response (p < 0.025); central hypothyroidism (overt + subclinical) was present in 74% of hyperPRL and in 60% of normoPRL patients (NS); 78% of hyperPRL and 55% of normoPRL patients had gonadotrophin deficiency (NS); growth hormone (GH) deficiency was present in 83% of hyperPRL and in 89% of normoPRL patients (NS); 73.3% of 75 evaluable pituitary hormone axes were abnormal in hyperPRL patients compared to 5 3.8% of 78 hormone axes in normoPRL patients (by metyrapone test to examine adrenal function, p < 0.025); and no significant differences in tumour grade and stage distribution were found between hyperPRL and normoPRL patients. It is concluded that hyperprolactinaemia in NFMA is associated with a higher prevalence of pituitary–adrenal dysfunction, which is likely to be explained at least in part by functional hypothalamic–pituitary interruption.
RPF Dullaart. Department of Endocrinology, University Hospital Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands