bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of corticotrophin-releasing hormone administration on growth hormone levels in acromegaly: in vivo and in vitro studies
Authors: Colao Annamaria , Merola Bartolomeo , Ferone Diego , Calabrese Maria Rosaria , Longobardi Salvatore , Spaziante Renato , Renzo Gianfranco Di , Annunziato Lucio , Lombardi Gaetano
Published: December 2008

Colao A, Merola B, Ferone D, Calabrese MR, Longobardi S, Spaziante R, Di Renzo G, Annunziato L, Lombardi G. Effect of corticotrophin-releasing hormone administration on growth hormone levels in acromegaly: in vivo and in vitro studies. Eur J Endocrinol 1994;131:14–19. ISSN 0804–4643

The ability of CRH to cause a paradoxical response of GH in acromegaly is still under debate. In this study, the effect of CRH administration on GH release was evaluated in a large series of patients with active acromegaly, both in vivo, compared to that of TRH and GnRH, and in vitro. The study was organized as follows. In vivo study: 30 acromegalic patients were submitted to TRH, GnRH, and CRH tests on non-consecutive days: blood samples were collected before and 10, 20, 30, 45, 60, 90, and 120 min after bolus. In nine patients the CRH test was repeated after a 3-month therapy with octreotide and at the dose of 300–600 μg sc thrice daily. In vitro study: CRH (10 nmol/l, 100 nmol/l, and 1 μmol/l) was tested on pituitary tumor tissue obtained in eight patients during transsphenoidal adenomectomy and immediately placed in sterile Ca2+ and Mg2+ free buffer phosphate. A paradoxical GH response to TRH (evaluated as a GH increase over 50% of basal values) was recorded in 19 patients (63.3%), whereas 7 patients (23.3%) responded to GnRH and 4 others to CRH (13.3%). TRH administration induced a maximal percent GH increase significantly greater than that induced by GnRH and CRH (p < 0.05). Octreotide caused the normalization of GH and insulin-like growth factorI levels in all the patients, as well as the disappearance of the GH paradoxical response to CRH in 3/4 patients. All four CRH responders and four CRH non-responders, used as controls, were surgically treated and adenomatous tissue was used for the in vitro study. No significant GH increase was found in the CRH non-responders and in the three CRH responders in whom the GH paradoxical response to CRH disappeared during octreotide treatment. Conversely, a significant GH increase (over 250% of pre-incubation values) after CRH administration was found in the remaining case. In conclusion, the results of the present study show that CRH is rarely able to stimulate paradoxical GH response in patients with active acromegaly and that the in vivo recorded GH release after CRH is in vitro reproducible only in extremely rare cases.

Annamaria Colao, Corso Europa 63, 80127 Napoli, Italy
Effects of repeated subcutaneous administration of recombinant human insulin-like growth factor I in adults with growth hormone deficiency
Authors: Thorén Maria C , Wivall-Helleryd Inga-Lena , Blum Werner F , Hall Kerstin E
Published: December 2008

Thorén MC, Wivall-Helleryd I-L. Blum WF, Hall KE. Effects of repeated subcutaneous administration of recombinant human insulin-like growth factor I in adults with growth hormone deficiency. Eur J Endocrinol 1994;131:33–40. ISSN 0804–4643

Insulin-like growth factor I (IGF-I) circulates bound to specific binding proteins (BPs) that modulate its effects at target cells. Hypoglycemia alters the serum levels of insulin-dependent IGFBPs and thus modifies the IGF-I action. We administered recombinant IGF-I (40 μg/kg body wt, from Kabi Pharmacia) in a morning dose (08.00 h) for seven consecutive days to six patients (21–47 years) with panhypopituitarism. This dose did not lead to hypoglycemia. Repeated blood sampling was performed on days 1 and 7, otherwise morning samples were drawn. The mean serum total IGF-I was maximal 3–4 h after the injection. A higher peak and basal value (p < 0.05) was observed on day 7 when compared to that observed on day 1. The concentrations were 237 vs 190 μg/l and 43 vs 22 μg/l. The mean free IGF-I increased concomitantly to 17 and 20 μg/l after 2–3 h on days 1 and 7. After 4 h, IGF-II was decreased (p <0.05) from 340 to 291 μg/l on day 1 and from 341 to 252 μg/l on day 7. The IGF-I area under the curve on days 1 and 7 was correlated to the IGFBP-3 levels. Only the patient with the highest IGFBP-3 level obtained IGF-I levels above 100 μg/l for 24 h. In spite of unchanged glucose levels, there was a modest suppression of insulin levels (p < 0.05) between 0 and 4 h from 102 to 78 pmol/l on day 1 and from 90 to 60 pmol/l on day 7 when the subjects were fasting. A small decline of mean potassium concentrations was found 2–6 h after the injection on day 1. During a week with daily injections, the morning serum IGF-I increased slightly in comparison to basal levels but no significant change in morning values of IGFBP-1, -2, -3, glucose and insulin were observed. Serum urea, creatinine, cholesterol and free fatty acid decreased significantly, indicating metabolic effects of IGF-I. Thus IGF-I has metabolic effects in doses not leading to hypoglycemia. To achieve a normal diurnal IGF-I level, recombinant IGF-I should be administered two or three times per 24 h in subjects with subnormal IGFBP-3 levels.

Marja Thorén, Department of Endocrinology and Diabetology, Karolinska Hospital, S-171 76 Stockholm, Sweden
The relationship between plasma osmolality and plasma vasopressin concentration is altered in old male Lewis rats
Authors: Terwel Dirk , Jolles Jellemer
Published: December 2008

Terwel D, Jolles J. The relationship between plasma osmolality and plasma vasopressin concentration is altered in old male Lewis rats. Eur J Endocrinol 1994;131:86–90. ISSN 0804–4643

Kidney dysfunction has been observed in aged humans and rats, the primary cause of which may reside in the kidney itself or in the hypothalamus. The latter possibility is suggested by the increased release of AVP in response to salt infusion in humans. The effect of age on the relationship between plasma osmolality and plasma AVP concentration has never been verified in an animal model. Therefore, in the present study, 9% salt solution was infused into adult and aged Lewis rats, and plasma AVP concentration and osmolality were measured. Basal plasma AVP concentration, osmolality and total water intake were not altered in aged Lewis rats as compared with adult animals, indicating the absence of overt disturbances in water homeostasis. Infusion of 9% salt solution resulted in a linear increase in plasma osmolality in both adult and aged rats. Plasma osmolality increased more with time in aged animals than in adult animals, suggesting an age-related difference in kidney function during salt infusion. Plasma AVP concentration increased 50% less with osmolality at relatively low osmolalities, but not at relatively high osmolalities. The altered relationship between plasma osmolality and plasma AVP concentration in rats with age may be related to changes in neurons monitoring osmolality or to changes in baroreflex regulation. The data suggest that reduced kidney function with age does not result from an altered relationship between plasma osmolality and plasma AVP concentration.

D Terwel, University of Limburg, Department of Neuropsychology and Psychobiology, PO Box 616, 6200 MD Maastricht, The Netherlands
Pharmacological characterization and autoradiographic localization of dopamine receptors in the human adrenal cortex
Authors: Amenta Francesco , Chiandussi Livio , Mancini Maurizio , Ricci Alberto , Schena Marina , Veglio Franco
Published: December 2008

Amenta F, Chiandussi L, Mancini M, Ricci A, Schena M, Veglio F. Pharmacological characterization and autoradiographic localization of dopamine receptors in the human adrenal cortex. Eur J Endocrinol 1994;131:91–6. ISSN 0804–4643

The pharmacological characteristics and the anatomical localization of dopamine D1-like and D2-like receptors were studied in sections of the human adrenal cortex using radioligand binding and autoradiographic techniques. [3H]SCH23390 was used as a ligand of D1-like receptors, whereas [3H]spiroperidol was used to label D2-like receptors. No specific [3H]SCH 23390 binding was detectable in sections of the human adrenal cortex. On the other hand, [3H]spiroperidol was bound to sections of the adrenal gland in a manner consistent with the labelling of dopamine D2-like receptor sites. The binding was time, temperature and concentration dependent, belonging in the range of concentrations of the radioligand used for a single class of high-affinity sites. The dissociation constant (Kd) averaged 2.7 nmol/l, whereas the maximum density of binding sites (Bmax) was 160 nmol/mg tissue. Experiments on the pharmacological specificity of [3H]spiroperidol binding to sections of the human adrenal cortex revealed that clozapine was the most powerful displacer of [3H]spiroperidol from sections of the human adrenal cortex. This suggests the presence in the human adrenal cortex of dopamine receptors of the D4 subtype. Light microscope autoradiography showed the highest density of specific [3H]spiroperidol binding sites in the zona glomerulosa and to a lesser extent in the zona reticularis. Only sparse [3H]spiroperidol binding sites were localized in the zona fasciculata. The possible functional consequences of this localization of dopamine D2-like receptor sites in the human adrenal cortex are discussed.

Francesco Amenta, Istituto di Farmacologia, Via Scalzino 5, 62032 Camerino, Italy
Anti-obesity effect of CL 316,243, a highly specific β3-adrenoceptor agonist, in mice with monosodium-l-glutamate-induced obesity
Authors: Yoshida Toshihide , Sakane Naoki , Wakabayashi Yasuo , Umekawa Tsunekazu , Kondo Motoharu
Published: December 2008

Yoshida T. Sakane N, Wakabayashi Y, Umekawa T, Kondo M. Anti-obesity effect of CL 316,243, a highly specific β3-adrenoceptor agonist, in mice with monosodium-l-glutamate-induced obesity. Eur J Endocrinol 1994;131:97–102. ISSN 0804–4643.

The effects of CL 316,243, a highly specific β3-adrenoceptor agonist (relative selectivities of 0, 1 and 100000 for β1-, β2- and β3-receptors, respectively), were evaluated in mice with monosodium l-glutamate (MSG)-induced obesity as well as in control mice injected with physiological saline instead of MSG. Both MSG- and saline-treated mice were divided into three groups and at 8 weeks of age received either CL 316,243 (0.1 or 1.0 mg/kg) or distilled water through a gastric tube for 2 weeks. CL 316,243 not only reduced white adipose tissue mass but also activated brown adipose tissue and systemic metabolism, and hence reduced body mass without affecting food intake. Furthermore, CL 316,243 decreased hyperglycemia and hypertriglyceridemia in MSG-treated mice. However, at the higher dose, CL 316,243 also increased liver triglyceride in MSG-treated mice. These observations suggest that CL 316,243 exerts an anti-obesity effect in mice with MSG-induced obesity and consequently may prove efficacious in the treatment of human obesity.

Toshihide Yoshida, First Department of Internal Medicine, Kyoto Prefectural University of Medicine, 465-Kajiicho, Hirokoji-Kawaramachi, Kamikyo-ku, Kyoto 602, Japan
Reduction in size of a thyrotropin-secreting pituitary adenoma treated with octreotide acetate (somatostatin analog)
Authors: Lee Eun Jig , Kim Kyung Rae , Lim Sung Kil , Lee Hyun Chul , Kim Dong Ik , Kim Sun Ho , Huh Kap Bum
Published: December 2008

Lee EJ, Kim KR, Lim SK, Lee HC, Kim DI, Kim SH, Huh KB. Reduction in size of a thyrotropin-secreting pituitary adenoma treated with octreotide acetate (somatostatin analog). Eur J Endocrinol 1994;131: 109–12. ISSN 0804–4643

We present a 55-year-old female with a thyrotropin (TSH)-secreting pituitary adenoma who had been treated with somatostatin analog octreotide acetate (SMS 201–995) for 4 months. Subcutaneous injection of 100 μg octreotide acetate twice daily resulted in significant reduction of the TSH, thyroid hormone, and tumor size. During the treatment, there was no evidence of any side effects. We may conclude that octreotide acetate administration is an effective treatment in patients with TSHsecreting pituitary adenoma for suppressing TSH hypersecretion and reducing the size of the tumor.

Eun Jig Lee, Division of Endocrinology, Department of Internal Medicine, Yong Dong Severance Hospital, Youngdong PO Box 1217, Seoul 135-270, Korea
Echographic diagnosis of pretibial myxedema in patients with autoimmune thyroid disease
Authors: Salvi Mario , De Chiara Flavia , Gardini Eliana , Minelli Roberta , Bianconi Lina , Alinovi Alberto , Ricci Roberto , Neri Fabrizio , Tosi Claudio , Roti Elio
Published: December 2008

Salvi M, De Chiara F, Gardini E, Minelli R, Bianconi L, Alinovi A, Ricci R, Neri F, Tosi C, Roti E. Echographic diagnosis of pretibial myxedema in patients with autoimmune thyroid disease. Eur J Endocrinol 1994;131:113–19. ISSN 0804–4643

In the present study we have evaluated the use of pretibial ultrasound for the diagnosis of pretibial myxedema (PTM). We studied 76 patients, 58 with Graves' disease, 13 with Hashimoto's thyroiditis and five with idiopathic hypothyroidism. Thirty-two normal subjects were also studied as controls. Sixty-four patients had associated ophthalmopathy. The ultrasound scanner was equipped with 10-and 13-MHz probes. Punch biopsies were carried out in 11 patients and tissue sections examined on a light microscope. On clinical examination 21 patients (28%) had suspected PTM. By ultrasound, we measured the thickness of dermis and subcutaneous tissue (Dl) and that including only deeper dermis (D2) in normal subjects to define the echographic parameters of normal pretibial skin. We then found increased skin thickness in 25 patients (33%), with mean Dl and D2 values significantly higher than those measured in controls (p < 0.00001). The echographic study was positive in 20 patients with ophthalmopathy (31%). Ultrasound showed increased skin thickness in 16 of 21 patients (76%) with clinically suspected PTM. Histopathological findings confirmed the presence of PTM in all the patients who underwent pretibial skin biopsy. We believe that the measurement of pretibial skin thickness by ultrasound may be useful for revealing the presence of PTM.

Mario Salvi, Cattedra di Endocrinologia, Università di Parma, Via Gramsci 14-43100 Parma, Italy
Antithyroid effects in vivo and in vitro of babassu and mandioca: a staple food in goiter areas of Brazil
Authors: Gaitan Eduardo , Cooksey Robert C , Legan Jim , Lindsay Raymond H , Ingbar Sidney H , Medeiros-Neto Geraldo
Published: December 2008

Gaitan E, Cooksey RC, Legan J, Lindsay RH, Ingbar SH, Medeiros-Neto G. Antithyroid effects in vivo and in vitro of babassu and mandioca: a staple food in goiter areas of Brazil. Eur J Endocrinol 1994;131:138–44. ISSN 0804–4643

Babassu (Orbignya phalerata), a palm-tree coconut fruit, mixed with mandioca (Manihot utilissima) is the staple food of people living in the endemic goiter area of Maranhao in Brazil, where goiter prevalence among schoolchildren was still 38% in 1986 despite an adequate iodine intake in most of the population. Therefore, the question arose as to whether or not the ingestion of babassu alone or mixed with mandioca contributed to the persistence of endemic goiter in this area of Brazil. In this investigation we examined the potential antithyroid effects of babassu and mandioca by means of in vivo studies in Sprague-Dawley rats, in vitro studies in porcine thyroid slices and using a purified porcine thyroid peroxidase (TPO) system. Samples of various edible parts of babassu and mandioca flour were homogenized and extracted in goitrogen-free water (GFW) for in vivo experiments, and in methanol (100 g/l), GFW or 0.06 mol/l phosphate buffer (pH 7.0) for in vitro experiments. The edible parts of babassu produced significant in vivo antithyroid effects (p < 0.05–< 0.001) in rats on a high iodine intake (14 μg I− day−1 · rat−1), as well as distinct and reproducible antithyroid and anti-TPO activities in both in vitro systems, their action being similar to that of the thionamide-like antithyroid drugs propylthiouracil and methimazole. The antithyroid action of aqueous extracts of mandioca flour in vivo and in thyroid slices in vitro was also evident by significant (p < 0.01–< 0.001) and pronounced inhibition of the iodide organification process; however, in contrast to babassu, methanol and aqueous extracts of mandioca flour caused little inhibition in vitro in the TPO system. Little or no effect was produced by babassu or mandioca on thyroid iodide transport by thyroid slices or in vivo in the rat, indicating that neither thiocyanate nor perchlorate-like compounds are responsible for their antithyroid effects. Results of this study provide direct experimental evidence, both in vivo and in vitro, of antithyroid effects of babassu and mandioca, supporting the hypothesis that this staple food is responsible, at least in part, for the persistence of goiter in the iodine-supplemented endemic region of Maranhao in Brazil.

Eduardo Gaitan, Endocrinology Section (151), VA Medical Center, 1500 E. Woodrow Wilson Drive, Jackson, MS 39216, USA
Increased prevalence of colonic adenomas in patients with acromegaly
Authors: Vasen Hans FA , van Erpecum Karel J , Roelfsema Ferdinand , Raue Friedhelm , Koppeschaar Hans , Griffioen Gerrit , van Berge Henegouwen Gerard P
Published: December 2008

Vasen HFA, van Erpecum KJ, Roelfsema F, Raue F, Koppeschaar H, Griffioen G, van Berge Henegouwen GP. Increased prevalence of colonic adenomas in patients with acromegaly. Eur J Endocrinol 1994;131:235–7. ISSN 0804–4643

Forty-nine acromegalics and 57 controls matched for age and sex underwent colonoscopy. The control group consisted of patients investigated because of atypical abdominal complaints compatible with irritable bowel syndrome or constipation. The exclusion criteria for both groups included: age over 75 years, previous colonic polyps or cancer, previous colonic surgery, rectal blood loss, anemia, previous abdominal radiation, sigmoidoscopy, colonoscopy or barium enema performed for any indication within 3 years prior to the present study. Colonoscopy was successful in reaching the cecum in 72 and 77% of the controls and acromegalics, respectively (p = NS). Eleven (22%) of 49 acromegalics had biopsy-proven colonic adenomas versus only five (9%) of the control group (p≤0.05). Multiple adenomas were found in three of the 11 acromegalics and in none of the controls. In five of these 11 patients and in only one of the controls, at least one adenoma was located in the right colon. In addition, acromegalics tended to have larger adenomas. The group of acromegalics with and without adenomas did not differ significantly in age or duration of active disease. In conclusion, the present study shows that acromegalic patients have an increased risk of developing colonic adenomas.

HFA Vasen, Department of Gastroenterology, Leiden University Hospital, Rijsnburgerweg 10, 2333 AA Leiden, The Netherlands
Low-dose growth hormone-releasing hormone tests: a dose–response study
Authors: Spoudeas Helen A , Winrow Andy P , Hindmarsh Peter C , Brook Charles GD
Published: December 2008

Spoudeas HA, Winrow AP, Hindmarsh PC, Brook CGD. Low-dose growth hormone-releasing hormone tests: a dose-response study. Eur J Endocrinol 1994;131:238–45. ISSN 0804–4643

We have evaluated parameters of the serum growth hormone (GH) concentration response to saline and 1-, 10- and 100-μg intravenous bolus doses of amide analogue of GH-releasing hormone (GHRH (1–29)NH2) given in random order to 10 adult male volunteers of median body weight 68 (60–90)kg. Compared with saline, both 10- and 100-μg GHRH(1–29)NH2 doses (but not 1 μg) resulted in significant peak GH responses (means and 95% confidence intervals: 24.03 (11.22–51.29) vs 26.09 (16.40–41.50) mU/l, respectively). Although the average rate of serum GH rise was similar after both 10 μg (2.05 (1.13–2.97) mU · l−1 · min−1) and 100 μg of GHRH(1–29)NH2 (1.52 (0.69–2.35) mU·1−1 · min−1; ANOVA F = 0.93, p = 0.35), the average rate of serum GH decline after peak GH was slower after the higher dose (10 μg vs 100 μg: 0.65 (0.40–0.90) vs 0.37 (0.23–0.50) mU·1−1·min−1; ANOVA F = 5.14, p = 0.04), suggesting continued GH secretion. Increasing GHRH(1–29)NH2 doses delayed the time to peak GH (1 μg: 7.00 (3.50–10.52) min; 10 μg: 15.80 (13.62–17.98) min; 100 μg: 24.80 (18.40–31.12) min) and serum GH levels were still elevated significantly 2 h after injection of 100 μg GHRH(1–29)NH2 compared with other doses (saline: 0.98 (0.48–2.04) mU/1; 1 μg: 0.68 (0.48–0.93) mU/1; 10 μg: 1.07 (0.56–2.04) mU/1; 100 μg: 5.01 (2.34–10.86) mU/l; ANOVA F = 11.10, p < 0.001). In a second study we tested five adult male volunteers with lower doses (0.5–10 μg) of GHRH(1–29)NH2. Consistent responses were observed only at doses equal to or greater than 2.5 μg and all occurred between 10 and 25 min. The estimated ed50 for GHRH(1–29)NH2 from the combined study data was 7.5 μg (0.08 μg/kg; range 0.06–0.12 μg/kg). The 10-μg dose of GHRH(1–29)NH2 was a maximal stimulus in all release parameters examined and GH peaks of < 15 mU/l (10th centile) should be considered potentially abnormal. Lower doses of GHRH(1–29)NH2 released GH quicker than higher doses, which simply prolonged the response, possibly by causing release from different pools. Our results suggest that sampling at 0, 10, 15, 20 and 25 min after a 10-μg dose of GHRH(1–29)NH2 will identify all GH peaks.

CGD Brook, The Endocrine Unit, Middlesex Hospital, Mortimer Street, London WIN 8AA, UK
Changes in calciotrophic hormones and biochemical markers of bone turnover in normal human pregnancy
Authors: Gallacher Stephen J , Fraser William D , Owens Owen J , Dryburgh Frances J , Logue Fraser C , Jenkins Andrew , Kennedy James , Boyle Iain T
Published: December 2008

Gallacher SJ, Fraser WD, Owens OJ, Dryburgh FJ, Logue FC, Jenkins A, Kennedy J, Boyle IT. Changes in calciotrophic hormones and biochemical markers of bone turnover in normal human pregnancy. Eur J Endocrinol 1994;131:369–74. ISSN 0804–4643

Plasma concentrations of parathyroid hormone-related protein (PTHrP), parathyroid hormone, alkaline phosphatase, osteocalcin and albumin-adjusted calcium were measured along with nephrogenous cyclic adenosine monophosphate (NcAMP) in 10 normal women longitudinally through pregnancy. In addition, an assessment of bone resorption was made in these same subjects by the measurement in true fasting urine specimens of the calcium/creatinine ratio (Ca/Cr), hydroxyproline/ creatinine ratio (HP/Cr), pyridinoline/creatinine ratio (Pyr/Cr) and deoxypyridinoline/creatinine ratio (Dpyr/Cr). The PTHrP level rose through pregnancy from (mean±sem) 0.8 ± 0.2 pmol/l in the first trimester to 2.7 ± 0.2 pmol/l 6 weeks postpartum (p < 0.0001). Serum alkaline phosphatase rose from 94 ± 8 U/l (first trimester) to 347 ± 25 U/l at term (p < 0.0001). A significant positive correlation was evident between PTHrP and alkaline phosphatase up to term (r = 0.44, p < 0.005). Parathyroid hormone concentrations remained unchanged during pregnancy but rose significantly postpartum from 1.8 ± 0.2 pmol/l (first trimester) to 3.1 ± 0.5 pmol/l (p < 0.0001). Similarly, osteocalcin, a marker of bone formative activity, remained unchanged through pregnancy but rose significantly at 6 weeks after delivery to 0.38 ± 0.05 nmol/l from 0.19 ± 0.03 nmol/l (first trimester) (p = 0.019). No significant change was noted in serum-adjusted calcium or NcAMP, either through pregnancy or at the postpartum assessment. Fasting urinary Ca/Cr fell through pregnancy from 0.70 ± 0.11 (first trimester) to a nadir of 0.19 ± 0.04 6 weeks postpartum (p = 0.007). Fasting urinary HP/Cr rose from 0.026 ± 0.003 (first trimester) to a peak of 0.049 ± 0.012 (third trimester), thereafter falling to 0.024 ± 0.002 6 weeks after delivery. Fasting urinary Pyr/Cr rose from 30.5 ± 1.7 (first trimester) to a peak of 58.3 ± 6.6 (term) (p = 0.009); Dpyr/Cr also increased through pregnancy from 9.9 ± 1.3 (first trimester) to 16.1 ± 1.7 (term) (p = 0.01). Previous studies have suggested that the placenta (during pregnancy) and breast milk (postpartum) are the main sources of PTHrP in pregnancy. This study illustrates that changes in plasma concentrations of PTHrP also can be demonstrated— although whether or not circulating PTHrP has a specific endocrine function is not clear.

SJ Gallacher, University Department of Medicine, Queen Elizabeth Building, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK
Histamine- and stress-induced prolactin secretion: importance of vasopressin V1- and V2-receptors
Authors: Kjær Andreas , Knigge Ulrich , Warberg Jørgen
Published: December 2008

Kjær A, Knigge U, Warberg J. Histamine- and stress-induced prolactin secretion: importance of vasopressin V1- and V2-receptors. Eur J Endocrinol 1994;131:391–7. ISSN 0804–4643

We investigated the involvement of arginine vasopressin (AVP) V1- and V2-receptors in the prolactin (PRL) secretory response to histamine (HA) or restraint stress stimulation in conscious male rats by selective blockade of AVP receptors using different antagonists. Histamine (270 nmol) administered intracerebroventricularly or 5 min of restraint stress stimulated PRL secretion 10–14-fold. Pretreatment with the selective V1- receptor antagonists [1-(p-t-butyl-β-mercapto-β, β-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-d-arginine] vasopressin or [1-(β-mercapto-β, β-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-arginine]vasopressin inhibited the PRL response to HA and restraint stress in a dose-dependent manner with maximal inhibition of 60%. The effect of the two antagonists was identical when equipotent antivasopressor doses were administered. The selective V2-receptor antagonist [1-(β-mercapto-β, β-cyclopentamethylene propionic acid)-2-d-isoleucine-4-isoleucine-8-arginine]vasopressin was unable to inhibit the PRL response significantly. Combined administration of the V1-receptor antagonist [1-(p-t-butyl-β-mercapto-β, β-cyclopentamethylene propionic acid)-2-(O-methyl)tyrosine-8-d-arginine]vasopressin and the V2-receptor antagonist inhibited the PRL response to HA to the same extent as that observed when the V1antagonist was administered alone. None of the antagonists used had any effect on basal PRL secretion. We conclude that AVP seems to play a role in the mediation of HA- and restraint stressinduced secretion of PRL, and that the AVP receptor involved is primarily of the V1 -type or similar to this.

Andreas Kjær, Department of Medical Physiology, Division of Endocrinology and Metabolism, The Panum Institute (Building 12.3), University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark
Circulating insulin-like growth factor II/mannose-6-phosphate receptor and insulin-like growth factor binding proteins in fetal sheep plasma are regulated by glucose and insulin
Authors: Gallaher BW , Oliver MH , Eichhorn K , Kessler U , Kiess W , Harding JE , Gluckman PD , Breier BH
Published: December 2008

Gallaher BW, Oliver MH, Eichhorn K, Kessler U, Kiess W, Harding JE, Gluckman PD, Breier BH. Circulating insulin-like growth factor II/mannose-6-phosphate receptor and insulin-like growth factor binding proteins in fetal sheep plasma are regulated by glucose and insulin. Eur J Endocrinol 1994; 131:398–404. ISSN 0804–4643

We have reported previously that levels of insulin-like growth factor I (IGF-I) and IGF-II in fetal sheep plasma decrease with maternal starvation and increase following an infusion of glucose to the starved fetus, while a fetal infusion of insulin elevates UGF-I alone. We now report the changes in the circulating IGF-II/M6P receptor and plasma IGF binding proteins (IGFBPs), as measured by western blotting and ligand blotting, respectively, in fetus and mother during this study. In fetal plasma, the circulating IGF-II/mannose-6-phosphate (M6P) receptor, IGFBP-3 and IGFBP-4 were reduced during starvation. While circulating IGF-II/M6P receptor and IGFBP-4 levels were increased following the fetal insulin or glucose infusion, IGFBP-3 was unchanged and increased only after 48 h of maternal refeeding. Both IGFBP-1 and IGFBP-2 increased with starvation but while IGFBP-1 levels returned to control values following both insulin and glucose infusion, levels of IGFBP-2 were not reduced significantly by either infusion or by refeeding. In maternal plasma, levels of IGFBP-3 and IGFBP-4 decreased while IGFBP-1 and IGFBP-2 increased after 48 h of starvation. Levels of each IGFBP were unaltered following the fetal infusions but returned to values obtained during the control period after refeeding. These data show that each of the IGF carrier proteins is sensitive of changes in nutrition, either acutely, such as IGFBP-1, or chronically, as for IGFBP-3. This suggests that the circulating IGFII/M6P receptor and the IGFBP's may modulate IGF activity in the fetus during different nutritional states.

BH Breier, Research Centre for Developmental Medicine and Biology, Department of Paediatrics, School of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand
Progestin treatment in the dog II. Effects on the hypothalamic–pituitary–adrenocortical axis
Authors: Selman PJ , Mol JA , Rutteman GR , Rijnberk A
Published: December 2008

Selman PJ, Mol JA, Rutteman GR, Rijnberk A. Progestin treatment in the dog. II. Effects on the hypothalamic–pituitary–adrenocortical axis. Eur J Endocrinol 1994;131:422–30. ISSN 0804–4643

The effects of two synthetic progestins, medroxyprogesterone acetate (MPA) and proligestone (PROL), on the hypothalamic–pituitary–adrenocortical (HPA) axis were studied in two groups of eight ovariohysterectomized dogs each. Eight injections of long-acting progestins were administered at 3-week intervals. Recovery of the HPA axis was studied in four dogs of each group in the following 6 months. Basal levels of adrenocorticotrophin (ACTH) and cortisol in plasma and the urinary corticoid/creatinine ratio were measured. The responsiveness of the HPA axis was investigated by stimulation with ovine corticotrophin-releasing hormone. Both MPA and PROL caused sawtooth patterns of supression of basal ACTH and cortisol levels in plasma, synchronous with the time of administration. The suppression of the adrenocortical component of the HPA axis was most pronounced. Adrenocorticotrophin production also was affected but to a lesser extent and occurred especially in PROL-treated dogs. Soon after the cessation of progestin administration ACTH levels increased, sometimes with a rebound. In both groups basal cortisol levels and urinary corticoid/creatinine ratios did not return to pretreatment levels until 6 months after the last progestin injection. It is concluded that MPA and PROL act as glucocorticoid agonists and suppress the HPA axis. The suppression at the adrenocortical level may last for 6 months.

JA Mol, Department of Clinical Sciences of Companion Animals, Utrecht University, PO Box 80.154, 3508 TD Utrecht, The Netherlands
Growth hormone-releasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging
Authors: Ghigo E , Arvat E , Rizzi G , Goffi S , Grottoli S , Mucci M , Boghen MF , Camanni F
Published: December 2008

Ghigo E, Arvat E, Rizzi G, Goffi S, Grottoli S, Mucci M, Boghen MF, Camanni F. Growth hormonereleasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging. Eur J Endocrinol 1994;131:499–503. ISSN 0804–4643

The reduced activity of the growth hormone (GH)–insulin-like growth factor I (IGF-I) axis in aging may contribute to changes in body composition. As this GH insufficiency is due to hypothalamic pathogenesis, the availability of GH-releasing peptides (GHRPs), such as GHRP-6 (His-d-Trp-Ala-Trp-d-Phe-Lys-NH2) which is active even after oral administration, might be useful to restore it. The aim of our study was to verify the effectiveness of oral administration of GHRP-6 in normal elderly subjects and to investigate whether its GH-releasing activity is maintained or vanishes after short-term oral treatment. Seven normal elderly women (aged 65–82 years) were studied. The effect of oral administration of 300 μg/kg GHRP-6 on GH secretion was investigated before and after 4 days of treatment with the hexapeptide given twice daily. The GH response to the maximal effective dose of GHRH (1 μg/kg iv) also was studied. Before treatment, oral administration of 300 μg/kg GHRP-6 elicited a clear GH rise (peak 10.7 ± 3.3 μg/l; AUC 353.1 ± 90.6 μg·l−1·h−1). which was significantly higher (p < 0.01) than that induced by intravenous GHRH (peak 5.1 ± 1.5 μg/l; AUC 106.5 ±43.9 μg · l−1·h−1). After 4 days of treatment with GHRP-6, the GH response to the hexapeptide was maintained, with a trend towards an increase (peak 16.8 ± 2.9 μg/l; AUC 499.8 ± 107.2 μg·l−1·h−1). The IGF-I levels were not increased significantly after treatment (77.1 ± 8.4 vs 84.1 ± 12.2 μg/l). In conclusion, our results demonstrate that, in aging, oral GHRP-6 administration elicits a GH response that is higher than the maximal effective dose of intravenous GHRH and that the effect of the hexapeptide does not vanish after short-term treatment. More prolonged treatment and/or more frequent administrations of GHRP-6 are likely needed to increase IGF-I levels.

F Camanni, Division of Endocrinology, Department of Pathophysiology, Ospedale Molinette, C.so Dogliotti 14, 10126 Torino, Italy
Serum 3α-androstanediol glucuronide measurements in children with congenital adrenal hyperplasia
Authors: Hatun Sükrü , Yordam Nurşen , Çalikoǧlu Ali Süha
Published: December 2008

Hatun Ş, Yordam N, Çalikoǧlu AS. Serum 3α-androstandiol glucuronide measurements in children with congenital adrenal hyperplasia. Eur J Endocrinol 1994;131:504–8. ISSN 0804–4643

To determine the value of 3α-androstanediol glucuronide (3-AG) measurements in children with congenital adrenal hyperplasia, we compared serum 3AG, 17-hydroxyprogesterone (17-OHP), androstenedione (A), testosterone (T) and dihydrotestosterone (DHT) levels and 24-h urinary 17-ketosteroid (17-KS) excretion in 42 female children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, including 27 with the simple virilizing and 15 with the salt-losing form. Their mean age was 74.5 ±48.5 months (range, 6–194 months). Twenty-four-hour urinary 17-KS excretion and serum 3-AG, A, T, DHT and 17-OHP levels were measured in the patients. The values were less than the mean + 2 sd of the control group in 63%, 74%, 67%, 69%, 60% and 31% of the patients, respectively. Serum 3-AG levels correlated with 24-h urinary 17-KS excretion (r = 0.66) and plasma A (r = 0.80), 17-OHP (r = 0.56), T (r = 0.79) and DHT (r = 0.62) levels. We conclude that serum 3-AG is a useful metabolic index in the management of children with congenital adrenal hyperplasia.

Şükrü Hatun, Türk-İş Blk, 274/7, Aydinlikevler, Ankara, Turkey
Influence of prolonged fasting on thyroid hormone modulation of lipolysis in isolated epididymal adipocytes of Wistar rats
Authors: Cheikh Rajae Ben , Chomard Philippe , Dumas Paul , Autissier Nicole
Published: December 2008

Ben Cheikh R, Chomard P, Dumas P, Autissier N. Influence of prolonged fasting on thyroid hormone modulation of lipolysis in isolated epididymal adipocytes of Wistar rats. Eur J Endocrinol 1994; 131:516–21. ISSN 0804–4643

Male Wistar rats, 3 weeks old, were thyroidectomized surgically, kept for 1 month at 25°C and then fasted for 3 days, with or without daily intraperitoneal injection of 3,5,3′-triiodo-l-thryonine (4.6 nmol T3/100 g body weight). Age-matched fed euthyroid rats were used as controls. All the experiments were carried out using isolated epididymal adipocytes. Basal lipolysis was higher during fasting in euthyroid or T3-treated adipocytes than in hypothyroid adipocytes. Adipocytes of fed hypothyroid rats were quite unresponsive to theophylline alone or combined with adrenaline or isoproterenol, whereas lipolysis was stimulated by these drugs in euthyroid or T3-treated adipocytes. Such a stimulated lipolysis was increased partially by fasting in hypothyroid adipocytes and was restored to a euthyroid level in T3-treated adipocytes. Lipolysis was more stimulated by adenosine deaminase in fasted euthyroid adipocytes than in fed ones. Hypothyroid and T3-treated adipocytes were unresponsive to adenosine deaminase except in fasted T3-treated rats. In these adipocytes, lipolysis was activated by the combination of adenosine deaminase plus theophylline. Finally, lipolysis was inhibited strongly in hypothyroidism while it was activated weakly by fasting. Lipolysis was inhibited slightly in fasted hypothyroid rats and thyroid hormone restored lipolysis. The findings are discussed in terms of the dual regulation of lipolysis by fasting and thyroid hormones.

N Autissier, Laboratoire de Chimie Analytique, UFR des Sciences Pharmaceutiques et Biologiques, 7 Boulevard Jeanne d'Arc, 21033 Dijon-cedex, France
Serotoninergic control of prolactin secretion in prepubertal male rats
Authors: Aguilar Enrique , Ranchal Antonio , Tena-Sempere Manuel , Pinilla Leonor
Published: December 2008

Aguilar E, Ranchal A, Tena-Sempere M, Pinilla L. Serotoninergic control of prolactin secretion in prepubertal male rats. Eur J Endocrinol 1994;131:547–54. ISSN 0804–4643

The role of the serotoninergic system in the control of prolactin (PRL) secretion has been studied in prepubertal male rats. Serum PRL concentration was measured in 16-day-old male rats at different times after the administration of 5-hydroxytryptophan (5-HTP), a precursor of serotonin (5-HT) synthesis, alone or in combination with fluoxetine, a specific inhibitor of 5-HT uptake; dl-p-parachlorophenylalanine (PCPA), an inhibitor of 5-HT synthesis; and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective agonist of 5-HT1A receptors. Also, serum PRL concentration and pituitary content were measured after 5-HTP administration in castrated males implanted with silastic capsules containing testosterone or 5α-androstane-3α,17β-diol (α-diol). We found that: the reduction in serotoninergic activity after PCPA administration did not modify serum PRL concentrations; the stimulatory effect of 5-HTP on PRL secretion was not observed before day 16; the effects of 5-HTP or 5-HTP and fluoxetine were similar in intact and orchidectomized males; a significant increase in PRL secretion took place after 8-OH-DPAT administration; the duration of the stimulatory effect of 5-HTP increased after α-diol treatment; and pituitary PRL content increased after 5-HTP injection in intact males and decreased in castrated males treated with testosterone or α-diol. Therefore, we conclude that: the PRL-releasing effect of 5-HTP remains after orchidectomy; activation of 5-HT1A receptors may mediate, at least partially, the effect of 5-HTP; testosterone and α-diol affect the duration of PRL release after 5-HTP administration differently; and testicular factors other than androgens might be involved in the effects of 5-HTP on PRL pituitary accumulation.

Enrique Aguilar, Department of Physiology, Faculty of Medicine, Córdoba University, 14004 Córdoba, Spain
Serum chromogranin A in the differential diagnosis of Cushing's syndrome
Authors: Nobels Frank RE , de Herder Wouter W , Kwekkeboom Dik J , Coopmans Willy , Mulder Andries , Bouillon Roger , Lamberts Steven WJ
Published: December 2008

Nobels FRE, de Herder WW, Kwekkeboom DJ, Coopmans W, Mulder A, Bouillon R, Lamberts SWJ. Serum chromogranin A in the differential diagnosis of Cushing's syndrome. Eur J Endocrinol 1994:131:589–93. ISSN 0804–4643

We evaluated whether measuring serum levels of chromogranin A, a marker of neuroendocrine tumours, could be useful in the differential diagnosis between pituitary, adrenal and ectopic causes of Cushing's syndrome. Thirty patients with Cushing's syndrome were studied. The localization of the tumours responsible was pituitary in 15, adrenal in 5 and ectopic in 10 patients. Serum concentrations of chromogranin A were measured in all patients. Petrosal sinus sampling for chromogranin A was performed in the cases with pituitary-dependent Cushing's syndrome. Immunohistochemical staining for chromogranin A was carried out on part of the tumour specimens. Slightly elevated serum levels of chromogranin A (range 223–262 μg/1) were detected in inferior petrosal sinus and peripheral venous samples from three patients with pituitary-dependent Cushing's syndrome. Serum chromogranin A showed no significant pituitary to peripheral gradient in these patients. Chromogranin A levels were not elevated in cases of adrenal Cushing's syndrome. Markedly elevated concentrations (range 270–13900 μg/1) were shown in seven of 10 patients with neuroendocrine tumours with ectopic adrenocorticotrophin (ACTH) and/or corticotrophin-releasing hormone (CRH) production. Widespread metastasis was present in all these cases. Subjects with "occult" carcinoid tumours, with limited spread, had normal chromogranin A levels Immunohistochemical staining for chromogranin A was positive in three out of five pituitary adenomas and in all neuroendocrine tumours with ectopic ACTH and/or CRH production, while it was negative in all adrenocortical tumour specimens. It is concluded that elevated serum levels of chromogranin A can serve as markers of neuroendocrine tumours with ectopic ACTH and/or CRH production. The circulating levels are dependent mainly on the size of the tumours. Serum chromogranin A is not useful in the diagnosis of so-called occult Cushing's syndrome, caused by ectopic ACTH and/or CRH secretion by small neuroendocrine tumours.

F Nobels, Department of Endocrinology, Onze Lieve Vrouw Hospital, 164 Moorselbaan, 9300 Aalst, Belgium
Insulin, insulin-like growth factor I (IGF-I) and IGF-II enhance basal and gonadotrophin-releasing hormone-stimulated luteinizing hormone release from rat anterior pituitary cells in vitro
Authors: Soldani Renza , Cagnacci Angelo , Yen Samuel SC
Published: December 2008

Soldani R, Cagnacci A, Yen SSC. Insulin, insulin-like growth factor I (IGF-I) and IGF-II enhance basal and gonadotrophin-releasing hormone-stimulated luteinizing hormone release from rat anterior pituitary cells in vitro. Eur J Endocrinol 1994;131:641–5. ISSN 0804–4643

The role of insulin-like growth factor I (IGF-I) and IGF-II on luteinizing hormone (LH) release is still unclear. The present study was performed to investigate modifications of basal and gonadotrophinreleasing hormone (GnRH)-stimulated (109 mol/l) LH release, induced by a 4-h and a 24-h incubation with physiological doses of IGF-I (1, 5 and 10 nmol/l) and IGF-II (5, 10 and 15 nmol/l) in comparison with insulin (0.0017, 0.1722 and 1.722 nmol/l), from primary cultures of male rat anterior pituitary cells. Both during the 4-h and the 24-h incubation, basal and GnRH-stimulated LH release were increased by IGF-I, IGF-II and insulin in a dose-dependent fashion. Present data confirm insulin's capability of potentiating anterior pituitary LH release from dispersed rat anterior pituitary cells in vitro, and reveal similar effects for physiological doses of IGF-I and IGF-II.

Renza Soldani, Instituto di Ginecologia Ostetricia e Fisiopatologia della Riproduzione Umana, Ospedale S. Giovanni di Dio, via Ospedale 46, 09124 Cagliari, Italy
Effect of 6-hydroxydopamine injection into the arcuate hypothalamic nucleus on the osmotic release of vasopressin in conscious rats
Authors: Yamaguchi Ken'ichi , Hama Hitoshi , Watanabe Kazuo , Yamaya Kanemitsu
Published: December 2008

Yamaguchi K, Hama H, Watanabe K, Yamaya K. Effect of 6-hydroxydopamine injection into the arcuate hypothalamic nucleus on the osmotic release of vasopressin in conscious rats. Eur J Endocrinol 1994;131:658–63. ISSN 0804–4643

The aim of the present study was to evaluate a role in vasopressin secretion of the catecholaminergic neurons, including the tuberohypophysial dopaminergic neurons situated in the arcuate hypothalamic nucleus. A neurotoxin, 6-hydroxydopamine (6 g/l), was injected locally into the arcuate nucleus and its effects on catecholamine levels of the hypothalamic tissue and the neurointermediate lobe, and on the plasma vasopressin concentrations before and during iv infusion (0.1 ml kg−1 min−1) of isotonic (0.15 mol/l) or hypertonic saline (2.5 mol/l), were examined in conscious rats. The infusion of hypertonic saline produced increases of plasma vasopressin 15 and 30 min later, accompanied by elevations of plasma osmolality, sodium, chloride and arterial pressure. The vasopressin response was potentiated markedly by the 6-hydroxydopamine injection performed 8 days before, which hardly affected the responses of the other variables. Histological examination indicated that the injection sites of 6-hydroxydopamine in those rats had been located in the area ranging from rostral to medial arcuate nucleus. The iv infusion of isotonic saline did not change plasma vasopressin, osmolality, sodium, chloride or arterial pressure, regardless of the presence or absence of pretreatment with 6-hydroxydopamine. It was confirmed that when 6-hydroxydopamine was injected into the arcuate nucleus region 8 days before, noradrenaline and adrenaline concentrations of the hypothalamic tissue containing the injection site were decreased remarkably, although we could not detect any signficant alteration in the dopamine concentration of the hypothalamic tissue or the neurointermediate lobe. On the basis of these results, we concluded that catecholaminergic neurons in the arcuate nucleus may act to inhibit osmotic vasopressin secretion.

Ken'ichi Yamaguchi, Department of Physiology, Niigata University School of Medicine, Asahimachi-Dori 1, Niigata City, Niigata 951, Japan
Thyroid-stimulating antibodies in sera from patients with Graves' disease are heterogeneous in epitope recognition
Authors: Ueda Yoshimichi , Sugawa Hideo , Akamizu Takashi , Okuda Jyoji , Ueda Michiko , Kosugi Shinji , Ohta Chizuko , Kihou Yukio , Mori Toru
Published: December 2008

Ueda Y, Sugawa H, Akamizu T, Okuda J, Ueda M, Kosugi S, Ohta C, Kihou Y, Mori T. Thyroidstimulating antibodies in sera from patients with Graves' disease are heterogeneous in epitope recognition. Eur J Endocrinol 1995;132:62–8. ISSN 0804–4643

Two synthetic peptides, P354-14 (amino acid nos. 354 to 367) and P338-16 (nos. 338 to 353), corresponding to the partial amino acid sequences of the hTSH receptor structure were studied for their ability to bind specifically serum IgGs from patients with Graves' disease and to inhibit thyroid stimulating TSH receptor antibody (TSH-R SAb) activity. IgG binding was measured by an ELISA using sera from 102 Graves', 20 Hashimoto patients, and 9 normal subjects. Both peptides showed significantly increased IgG binding of Graves' sera compared with those of Hashimoto and normal sera. There was a significant correlation (r = 0.529) between the amount of IgG bound by the two peptides, but neither of these values correlated well with their TSH-R SAb activity nor thyrotropin-binding inhibitor TSH receptor antibody (TSH-R IAb) activity. TSH-R SAb inhibiting effects of these peptides were then analysed by measuring TSH-R SAb activity after incubation with the peptides. Among eight Graves' IgGs tested the TSH-R SAb activity of three was inhibited by both peptides, two were inhibited only by P354-14 and three were not affected by either. These TSH-R SAb inhibiting effects were dose-dependent and reproducible. To confirm these findings, a peptide-sepharose gel affinity absorption study was performed. Eleven Graves' IgGs were applied to both peptide gels and the TSH-R SAb activity of the unabsorbed fraction was measured. The TSH-R SAb activity of five IgGs was strongly absorbed only by P354-14 and five others were absorbed by both peptides to an almost similar extent. One IgG was not affected by either of the peptides. None of the IgG activities tested was absorbed only or predominantly by P338-16. Most of Graves' IgGs could bind to region no. 338 to no. 367 of the hTSH receptor. There was apparent heterogeneity among Graves' TSH-R SAb IgGs as shown by their absorption by the peptides, and the existence of at least three heterogeneous species in epitopic recognition among Graves' TSH-R SAb was demonstrated.

Toru Mori, Department of Laboratory Medicine, Kyoto University School of Medicine, 54-Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-01, Japan