bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrathyroidal thyroglobulin in streptozotocin-diabetic rats
Authors: Lamas Luis , Jolin Trinidad
Published: December 2008

Abstract. In order to elucidate whether or not the 'coupling defect' observed in thyroids from diabetic rats is due to a structural defect of intrathyroidal thyroglobulin (Tg), the sedimentation pattern and the stability of the thyroidal soluble iodoproteins were studied in control (C), food restricted (FR), diabetic (D) and insulin-treated diabetic (D+I) rats fed a low iodine diet either with (NID) or without (LID) iodide supplementation and labelled with 125I: 1) acutely, 24 h prior to sacrifice and 2) chronically, by feeding the corresponding diet labelled for 60 days. Diabetes resulted in a decrease of thyroidal weight, an increase of both thyroidal 127I content and concentration and decreased plasma TSH, irrespective of the diet. Insulin treatment reversed these alterations. Food restriction led to an intermediate situation between C and D. The iodoamino acid distribution in the acutely labelled thyriodal soluble iodoproteins showed a significant increase in the percent of organified 125I found as iodotyrosines (MIT and DIT) and a decrease of that found as iodothyronines (T3 and T4) both in D and FR. However, in the isotopically equilibrated groups, no differences were found except in LID-D where a slight increase in DIT and a decrease in T3 was found as compared to the corresponding control. The sedimentation patterns of both acutely and chronically labelled thyroidal soluble iodoproteins from all experimental groups displayed two peaks. The main one, corresponding to Tg, had a slightly lower sedimentation coefficient than the 19 S internal marker run in parallel, while the second one, relatively small, formed probably by dissociation of the main Tg peak, sedimented more slowly (12–14 S). D and FR showed no differences with C and D+I, however, the Tg molecule from D and FR was more resistant to the dissociating effect of dialysis against low ionic strength buffer than the corresponding C and D+I groups. This increase in stability of Tg in D and FR might be due to their relatively higher iodine content and/or lower TSH stimulation. In conclusion, the results obtained suggest that the low T3 and T4 content of thyroidal soluble iodoproteins found in diabetic rats is not the direct consequence of a major structural alteration in the Tg molecule.
Effect of clomiphene citrate on the in vitro release of LH and FSH by the pituitary gland of the long-term ovariectomized rat pretreated with LRH or with LRH and oestradiol benzoate
Authors: Schuiling G. A. , Moes H. , Koiter T. R.
Published: December 2008

Abstract. The effect of a combined in vivo pre-treatment with luteinizing hormone-releasing hormone (LRH) and either oestradiol benzoate (OB), clomiphene (-citrate) or OB plus clomiphene on the autonomous and the supramaximally LRH-stimulated in vitro secretion of LH and FSH by pituitary glands of long-term ovariectomized (OVX) rats was studied using a hemi-pituitary perifusion system. The concentration of LRH in the perifusion medium was 1 μg/ml. Pre-treatment with LRH during 5 days was effected by means of sc implanted Alzet® osmotic minipumps; control rats received a piece of silastic with the dimensions of a minipump. OB, 3 μg/injection, clomiphene 100 μg/injection or solvent were given on days 2 and 4 (day of perifusion: day 5). In rats not pre-treated with LRH neither OB, nor clomiphene changed the content of the pituitary gonadotropin stores. There was only a small but significant positive effect of the combined treatment with OB and clomiphene on the pituitary FSH content. LRH (partly) depleted the gonadotropin stores. This effect of LRH was potentiated by OB, but not by clomiphene. Clomiphene prevented the depletion-potentiating effect of OB. OB raised the LRH-stimulated secretion of LH and FSH as well as the autonomous secretion of LH. Clomiphene raised the LRH-stimulated (not the autonomous) secretion of LH and FSH. OB plus clomiphene had the same effect as OB alone. Clomiphene also raised the LRH-stimulated secretion of LH and FSH after pre-treatment with LRH, but OB did not do so: LRH prevented the stimulatory effect of OB but not of clomiphene. OB plus clomiphene had the same effect as OB alone. The absence of a stimulatory effect of OB on the LRH-stimulated secretion of LH and FSH in the LRH-pretreated rat appeared to be due to the very low gonadotropin content of the pituitary glands after pre-treatment with LRH and OB: the effect of OB on the LRH-responsiveness proper (i.e. release of LH and FSH as related to the pituitary LH and FSH content) remained stimulatory. Also clomiphene enhanced the LRH-responsiveness proper, but this drug cannot potentiate the gonadotropin stores-depleting effect of LRH. These results demonstrate that clomiphene exclusively 'behaves' like an oestrogen-agonist, able to enhance the LRH-stimulated gonadotropin secretion. Also in the LRH-pre-treated rat clomiphene acts like an oestrogen-agonist, but unlike oestradiol clomiphene cannot potentiate the LRH-induced depletion of the pituitary gonadotropin stores. Therefore, it can also raise the LRH-stimulated secretion of LH and FSH in the LRH-pre-treated OVX rat.
The calcium antagonist diltiazem inhibits calcification enhanced by calcitonin in growth cartilage of rats in ethane-1-hydroxy-1,1-diphosphonate (EHDP)-induced rickets
Authors: Eguchi Masao , Shibata Kenichiro , Wada Fumio , Kawamura Hideya , Shimauchi Takashi , Shiota Etsuji , Sugioka Yoichi
Published: December 2008

Abstract. In an animal model of human rickets developed by giving a short-term administration of large doses of EHDP to young rats, concomitant administration of [Asu1,7]eel calcitonin (CT) with EHDP resulted in the promotion of calcification in growth cartilage. In an attempt to clarify the mechanisms related to the accelerated calcification due to CT, the effects of diltiazem, a calcium antagonist, were studied. Diltiazem suppressed, in a dose-dependent manner, the accelerated calcification due to CT in the growth cartilage, as determined by findings on the soft X-ray photos, contact microradiograph and light microscopic histology of the proximal region of the tibia. This suppression was only evident when diltiazem and CT were given concomitantly. If it is assumed that diltiazem inhibits the entry of calcium ion into the cells of growth cartilage, in the same manner as seen in case of smooth muscle and myocardial cells, then our results indicate that intracellular concentrations of calcium might play an important role in the occurrence of accelerated calcification due to CT.
Serum levels of insulin-like growth factor (IGF) and IGF-binding protein in constitutionally short children and adolescents
Authors: Binoux Michel , Gourmelen Micheline , Girard François
Published: December 2008

Abstract. Serum insulin-like growth factor (IGF) and IGF-binding protein (IGF-bp) levels were studied in 92 constitutionally short children and adolescents (height < mean for age −2 sd) and in 13 subjects after completion of growth. IGF levels increased with age in a manner similar to that in normal subjects, but at lower levels (P < 0.001). The values were 0.41 ± 0.03 sem U/ml in 1 to 5 year old children, 0.72 ± 0.03 U/ml in 6-to 16 year old prepubescent children and 0.95 ± 0.05 U/ml during puberty. IGF-bp levels developed in a similar way, the values being 0.45 ± 0.06, 0.61 ± 0.04 and 0.85 ± 0.06 U/ml, respectively, for the three periods considered. Both IGF and IGF-bp levels in each of the three groups were significantly lower than those in normal subjects at the same stage of development. After fusion of the epiphyses, IGF and IGF-bp levels were within the normal range. A longitudinal study was undertaken in 15 subjects, showing increases in height corresponding with increases in IGF levels. For all the subjects studied during their growth period, there was a correlation between height age and IGF levels (r = 0.64, P < 0.001). All the subjects exhibited a normal rise in GH levels following stimulation. Although the possibility of quantitative or qualitative disorders of GH biosynthesis cannot be excluded in some of the cases, our data are compatible with the hypothesis that the growth retardation observed in constitutionally short children results, at least in part, from insufficient IGF production during post-natal growth.
Characterization of α-MSH-like immunoreactivity in human plasma
Authors: Kortlandt W. , De Rotte A. A. , Arts C. J. M. , Croughs R.J. M. , Thijssen J. H. H.
Published: December 2008

Abstract. We report new information on the presence of α-melanotropin(α-MSH)-like immunoreactivity in the peripheral circulation of the adult human. Pooled blood from 20 patients with non-endocrine diseases was subjected to a Sep-pak pre-purification followed by a high pressure liquid chromatographic (HPLC) fractionation. The eluate from the HPLC column was analyzed by a radioimmunoassay (RIA) specific for the C-terminal part of the α-MSH molecule. From this it appeared that α-MSH was the major α-MSH-like immunoreactive peptide present in human blood with a level of 2–5 pg/ml. This level is similar to the one determined by direct measurements in Sep-pak pre-purified human plasma (median 2.0 pg/ml, n = 11). Des-acetyl α-MSH was present in human blood in only a minor quantity. We discuss this finding in view of earlier reports on α-MSH-like immunoreactivity in human pituitary tissue.
Influence of terbutaline on TRH-induced prolactin and thyrotropin release in normal subjects
Authors: Röjdmark Sven
Published: December 2008

Abstract. To investigate whether terbutaline (T) influences the release of prolactin (Prl) and/or thyrotropin (TSH) from the anterior pituitary, 25 μg thyrotropin-releasing hormone (TRH) was injected iv in 7 normal subjects who were pre-treated orally with either T or placebo. The TRH-induced Prl response, as reflected by the Prl incremental area, was more pronounced after priming with placebo (2071 ± 606) than after T (1391 ± 434; P < 0.05). In contrast, the TRH-elicited TSH responses did not differ significantly after the two pre-treatments. When TRH was given to 8 additional individuals on iv background infusion of either T or saline, the Prl response was significantly larger during saline (2123 ± 354) than during T infusion (1540 ± 235; P < 0.01), whereas the TSH responses were of similar magnitudes. Six subjects, given 25 μg TRH iv on background infusion of T or saline, were also given propranolol orally before commencement of the T infusion and placebo before the saline infusion. This resulted in similar Prl responses and also in similar TSH responses, during the two background treatments. The results imply that oral as well as iv administration of T has inhibitory influence on human lactotrophs, but lacks measurable effect on thyrotrophs.
Improved enrichment of functionally intact anterior pituitary cells by sequential centrifugal elutriation and density gradient sedimentation
Authors: Scheikl-Lenz B. , Sandow J. , Herling A. W. , Träger L. , Kuhl H.
Published: December 2008

Abstract. By centrifugal elutriation and subsequent Percoll density gradient centrifugation, we obtained highly enriched cell populations of the anterior pituitary of ovariectomized adult rats. Enrichment of somatotrophs, gonadotrophs and mammotrophs was 90%, 80% and 77%, respectively (determined by immunocytochemistry). 41% of the GH-cells showed a medium cell size and the highest density. 52% of the LH-cells and 44% of the FSH-cells were found within the population of the large and medium-dense cells. 69% of the prolactin-cells belonged to the small-sized cells with low density. Thyrotrophs were found within all of the size ranges. The majority of the corticotrophs (82%) showed a small cell size. The enriched somatotrophs, LH-gonadotrophs, and mammotrophs responded to GRF, LRH and TRH. Before and after enrichment, somatotrophs and mammotrophs showed the same responsiveness to releasing hormones. In contrast, enriched LH-gonadotrophs exhibited a higher responsiveness to LRH than unfractionated LH-gonadotrophs.
Modulation of LH-secretion in ovariectomized ewes by constant infusions of oestradiol and 4-hydroxyoestradiol: effects of varying infusion times and of high oestrogen doses
Authors: Emons G. , Schuppe H. , Peter M. , Brack C. , Ball P.
Published: December 2008

Abstract. Ovariectomized ewes were infused for different times (2–24 h) during the breeding season (September to Februray) with oestradiol (E2, 2 μg/h) or the catecholoestrogen 4-hydroxyoestradiol (4-OHE2, 10 μg/h). At these infusion rates comparable plasma levels of E2 and 4-OHE2 were obtained when steady state was reached after 3 h (E2: 20 ± 4 pg/ml; 4-OHE2: 22 ± 3 pg/ml). When E2 was infused for at least 6 h, all animals had significant LH-surges, starting 14-16 h after the beginning of oestrogen treatment, even when E2 was infused for up to 24 h. 4-OHE2, however, had only to be infused for 4 h to induce significant LH-surges in all animals tested. When E2 was infused for 12 h at a rate of 100 μg/h, the LH-surges in these ewes were significantly lower than the LH-surges in the same animals treated for 12 h with E2at a rate of 2 μg/h.

These data indicate:

Once E2 has been administered at a specific infusion rate for a critical time period of 6 h, LH-surges occur, no matter whether the E2-infusion is continued or stopped.

For the catecholoestrogen 4-OHE2 this critical time period amounts only to 4 h, if comparable plasma levels of either oestrogen are achieved. This might hint at a prolonged intracellular action of 4-OHE2 as compared to E2.

At extremely high infusion rates of E2 (100 μg/h for 12 h) the positive oestrogen effect is significantly impaired, a finding supporting the concept of a bell-shaped dose-response relationship between oestrogens and their positive effect on LH-secretion.
Compensated 131I-therapy of solitary autonomous thyroid nodules: effect on thyroid size and early hypothyroidism
Authors: Hegedüs Laszlo , Veiergang Dagmar , Karstrup Steen , Hansen Jens Mølholm
Published: December 2008

Abstract. Thyroid function and thyroid gland volume, ultrasonically determined, were investigated in 27 hyperthyroid patients with solitary autonomous thyroid nodules before and during one year after 131I-treatment. Total thyroid volume decreased gradually from 40.9 ± 3.5 ml (mean ± sem) before treatment to 23.9 ± 1.8 ml (P < 0.001) at 3 months after 131I-treatment. No further change was observed. All but two patients received only one dose of 131I, and in spite of a significant decrease also of the non-adenoma side of the gland, none became hypothyroid. We conclude that 131I-therapy has an important place in the treatment of solitary autonomous thyroid nodules since all our patients became euthyroid within 3 months, only 2 of 27 patients needed more than one dose of 131I, no cases of hypothyroidism occurred, and thyroid volume was substantially decreased.
Enzyme-linked immunosorbent assay of autoantibodies reacting with thyroid plasma membrane antigens in sera of patients with autoimmune thyroid diseases
Authors: Gardas Andrzej , Rives Kathleen L.
Published: December 2008

Abstract. A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for the detection of autoantibodies reacting with thyroid plasma membrane antigens has been established. Autoantibodies reacting with thyroid plasma membrane antigens were detected by the ELISA in 95% of untreated hyperthyroid Graves', 68% of antithyroid drug-treated Graves' up to four months of the therapy, in 62% of Hashimoto's thyroiditis and in 8.9% of toxic nodular goitre. The ELISA was negative in 100% healthy blood donors, 100% non-toxic nodular goitre, in 12 patients with rheumatoid arthritis, 18 patients with scleroderma and 94% of patients with systemic lupus erythematosus. The mean value of autoantibodies titre was higher in untreated hyperthyroid Graves' (1:84 000) and lowest in positive patients with autoimmune disease of non-thyroid origin (1:4000). The cross-reactivity of antimicrosomal antigen antibodies was below 10%; there was no influence of antithyroglobulin antibodies on the ELISA; and most of the autoantibodies react with plasma membrane antigens different from the TSH binding sites.
Steroidogenesis and cAMP production in isolated avian granulosa cells during follicular maturation: Lack of positive correlation
Authors: Asem Elikplimi K. , Hertelendy Frank
Published: December 2008

Abstract. Luteinizing hormone- and forskolin-induced acute steroidogenesis and cAMP production were studied in dispersed chicken granulosa cells in relation to follicular maturation. Cells isolated from the 6 largest preovulatory follicles (F1-F6) were used in this study. Basal steroidogenic activity increased with progressive maturation of the follicle without a corresponding rise in basal cAMP production. Both LH- and forskolinpromoted progesterone production was directly correlated with the maturational stage of the follicle and the dose of the agonists. On the other hand, LH caused the greatest increase in cAMP production in the third and fourth largest preovulatory follicles (F3-F4), whereas forskolin-stimulated cAMP accumulation was maximal in the least mature granulosa cells (F5-F6). Thereafter it decreased in proportion with follicular development. It is concluded that LH-induced acute steroidogenesis in chicken granulosa cells is not positively correlated with cAMP production during the last few days of follicular maturation. Therefore the steroidogenic responsiveness of granulosa cells of the largest follicle to LH cannot be ascribed solely to receptor-coupled adenylate cyclase activity. As shown by the forskolin experiment, the intrinsic activity of the adenylate cyclase-cAMP system is greatest in the small F5, F6 follicles which respond only minimally in terms of steroidogenesis to either a receptor dependent agonist (LH) or a nonreceptor agonist (forskolin).
Transient lack of response to TSH of human cultured thyroid cells obtained from hyperfunctioning tissue
Authors: Tanini Annalisa , Brandi Maria Luisa , Modigliani Umberto , Rotella Carlo M. , Toccafondi Roberto
Published: December 2008

Abstract. TSH-induced cAMP accumulation in cells obtained from normal and pathological thyroid tissue was studied during the first 12 days of primary culture. In normal thyroid tissue cultures (N = 7), the response of cAMP to TSH was present from the second day of culture and reached its maximum after 8 days. A similar behaviour was observed in cultures obtained from euthyroid sporadic goitres (N = 8), even if the rate of response was slightly lower than that of normal tissue. Similarly, cultured cells from euthyroid 'autonomous' nodules (N = 8) appeared to be responsive to TSH during the period of study, but the rate of response was also lower than in the controls. On the contrary, in cultures obtained from toxic adenomas (N = 5) and from diffuse toxic goitres (N = 5) the response to TSH was absent during the first 4 days of culture. The cells became sensitive to TSH from 6 and 6 day onwards, with the rate of response increasing progressively and reaching its maximum on day 12. Finally, in cultured cells obtained from different areas of multinodular toxic goitres (N = 4), the response to TSH was similar to that of euthyroid goitres in cells prepared from 'cold' areas, and to that of toxic adenomas in cells obtained from 'hot' areas. The present data demonstrate the existence of an inhibitory action of unknown factors, possibly iodothyronines or thyroglobulin, on the TSH effect in short-term cultures obtained from thyrotoxic tissues. A normal TSH responsiveness can be restored when the culture is prolonged.
Primary adrenocortical micronodular adenomatosis causing Cushing's syndrome. Effects of ketoconazole on steroid production and in vitro performance of adrenal cells
Authors: Oelkers W. , Bähr V. , Hensen J. , Pickartz H. , Exner P. , Fenner A. , Harendt H.
Published: December 2008

Abstract. Mild Cushing's syndrome was diagnosed in a 35 year old woman. Elevated plasma and urinary cortisol levels were unsuppressible with up to 32 mg dexamethasone per day. Aldosterone, 18-OH-corticosterone and testosterone in plasma were normal and dehydroepiandrosterone-sulphate was low. No adrenal tumour was found by CT or adrenal venography, and bilateral cortisol secretion was demonstrated by steroid measurements in adrenal venous blood. A circadian rhythm of plasma cortisol was absent. Plasma ACTH was suppressed, even after injection of CRH, during insulininduced hypoglycaemia and after metyrapone administration, which led to a large fall in plasma cortisol but to a subnormal rise of plasma 11-deoxy-cortisol. The clinical diagnosis of primary micronodular adenomatosis of the adrenal gland was histologically confirmed, when the patient finally underwent bilateral adrenalectomy. In vitro, the adrenal cells did not produce more cortisol and aldosterone than adrenal cells from cadaver kidney donors. In vivo and in vitro, cortisol was slightly less than normally responsive to ACTH. Intermittent treatment of the patient with 800 mg/day of ketoconazole led to a rapid fall of cortisol secretion and clinical signs of adrenocortical insufficiency. Treatment for 7 weeks with 200–400 mg ketoconazole per day reduced plasma and urinary cortisol less dramatically into the normal range. This case unequivocally documents autonomous dysfunction of the adrenal cortex in this rare form of Cushing's syndrome and the efficacy of ketoconazole in the treatment of ACTH-independent hypercortisolism.
Maintenance of complete but quantitatively reduced spermatogenesis in hypophysectomized monkeys by testosterone alone
Authors: Marshall G. R. , Jockenhövel F. , Lüdecke D. , Nieschlag E.
Published: December 2008

Abstract. In order to investigate whether testosterone can maintain spermatogenesis in the absence of FSH in primates, four cynomolgus monkeys were hypophysectomized and implanted with 20 5-cm-long testosteronefilled silastic capsules within 45 min of pituitary ablation. Thereafter the serum levels of testosterone were elevated about 9-fold over presurgical levels. Testicular volumes declined to 60% of presurgical values. Testicular concentrations of testosterone were 50–180% of presurgical levels. Germ cell numbers were reduced to 30–50% of presurgical values and germ cell ratios suggested that the reduced numbers of all advanced germ cells were due to a decrease in the efficiency of proliferation of B spermatogonia. A fifth monkey was left untreated following hypophysectomy. Its serum testosterone was as low as that of castrated monkeys, and the testicular volume declined to 30% of that before surgery. Primitive spermatogonia were the only germ cells present 13 weeks after surgery. Thus, in primates testosterone alone maintains the complete process of spermatogenesis, however, spermatogonial proliferation is impaired in the absence of FSH.
Peripheral hormone levels in healthy subjects during controlled fasting
Authors: Tegelman Ragnar , Lindeskog Pia , Carlström Kjell , Pousette Åke , Blomstrand Rolf
Published: December 2008

Abstract. The effect of one week of controlled fasting (3 1 of fluid containing 50 g of carbohydrate/day) upon the serum levels of hormones, sex hormone binding globulin, and albumin was studied in healthy subjects. Fasting caused decreased levels of prolactin and T3, no changes in the levels of TSH, FSH, LH, dehydroepiandrosterone, 4-androstene-3,17-dione, total oestrone, and total testosterone, and increased levels of cortisol, dehydroepiandrosterone sulphate and albumin. A significant positive correlation was found between albumin and dehydroepiandrosterone sulphate. Fasting rapidly increased the levels of sex hormone binding globulin and decreased the percentage of free testosterone and the calculated free testosterone level in both sexes. A decreased metabolic clearance of certain steroids (cortisol, dehydroepiandrosterone sulphate) owing to an increased protein binding may be one of the endocrine consequences of fasting. An increased protein binding of testosterone may be outweighed by a decreased gonadal production, thus resulting in an unchanged total testosterone level. The increased sex hormone binding globulin level could not be explained by changes in gonadal and thyroid hormones.
Cushing's syndrome and autonomous thyroid nodules, a variant of multiple endocrine neoplasia?
Authors: Semple C. G. , Thomson J. A.
Published: December 2008

Abstract. Over a 20 year period 4 of 40 (10%) female patients with Cushing' syndrome also had a solitary thyroid nodule. In 3 cases this was an autonomous 'hot' nodule. In the same population only one case of presumed Graves' disease was seen. It is postulated that the association of autonomous thyroid nodule and Cushing's syndrome may represent a variant of multiple endocrine neoplasia.
Serum thyroid autoantibodies as a risk factor for development of hypopthyroidism after radioactive iodine therapy for single thyroid 'hot' nodule
Authors: Mariotti Stefano , Martino Enio , Francesconi Marcello , Ceccarelli Claudia , Grasso Lucia , Lippi Francesco , Baschieri Lidio , Pinchera Aldo
Published: December 2008

Abstract. Hypothyroidism is often observed after radioiodine treatment in Graves' disease, but it is considered a rare complication in single hyperfunctioning thyroid nodule ('hot' nodule). This concept has been recently challenged, but the available data are conflicting. In the present study we therefore assessed the development of permanent hypothyroidism in 126 patients with thyroid hot nodule treated with 131I (180 μCi/g of estimated nodule weight, total dose 5.5–28.9 mCi). Follow-up ranged between 1 to 11 years. Hypothyroidism was observed in 5 (4%) patients, corresponding to a cumulative incidence by life-table analysis of 4.8% ten years after treatment. No relationship was found between the development of hypothyroidism and the size of the nodule or the total amount of administered dose. Fifty-six patients with euthyroid hot nodule at the time of treatment had higher cumulative incidence of hypothyroidism after 10 years (9.7%) than those with toxic adenoma (1.5%) (0.1 > P > 0.05 by logrank test). When the patients were analyzed according to the presence or absence of serum antithyroglobulin and/or antithyroid microsomal autoantibodies, the prevalence of hypothyroidism after 131I treatment was higher (4/25 = 16%) in patients with significant serum antibody titres (≥ 1/400 by pasive haemagglutination), when compared to that observed in subjects with negative antibody tests (1/101 = 1.0%). Life-table analysis showed in antibody positive patients a cumulative incidence of hypothyroidism after 10 years of 18.0% vs 1.4% in antibody negative patients (P <0.001 by log-rank test). In conclusion, the present data provide the first evidence that coexistent thyroid autoimmunity is a significant risk factor for the development of hypothyroidism in patients with hot nodule treated with radioiodine.
End-organ resistance to PTH infusion in hypercalcaemic and normocalcaemic patients with solid tumours
Authors: Naafs M. A. B. , Fischer H. R. A. , van der Velden P.C. , Mulder H. , Hackeng W. H. L. , Schopman W. , Koorevaar G. , Silberbusch J.
Published: December 2008

Abstract. Ten hypercalcaemic patients with solid tumours were studied to evaluate the renal response on PTH infusion as assessed by nephrogenous cAMP excretion and maximum tubular re-absorption of phosphate. In addition, 20 normocalcaemic patients, 11 with an adenocarcinoma and 9 with a squamous cell carcinoma, were studied. All cancer patients had moderately extensive disease. Results were compared with those of 9 patients with primary hyperparathyroidism and with 10 elderly controls. All groups studied had comparable renal function, magnesium and 25-hydroxy-vitamin D levels. Comparable results were obtained in patients with an adenocarcinoma and in controls. cAMP response (Δ nephrogenous cAMP) was significantly lower in the hypercalcaemic patients with a solid tumour compared with the controls (8.13 ± 4.68 nmol/100 ml glomerular filtrate vs 29.52 ± 25.62 nmol/100 ml glomerular filtrate; P < 0.005). In the group of patients with primary hyperparathyroidism Δ nephrogenous cAMP was 13.41 ± 7.54 nmol/100 ml glomerular filtrate (P < 0.06 vs controls). The group of patients with a squamous cell cancer showed an intermediate value of 14.83 ± 10.74 nmol/100 ml glomerular filtrate (P < 0.025 vs the normocalcaemic adenocarcinoma patients, but NS vs controls). In two hypercalcaemic patients with a solid tumour in whom PTH infusion was repeated after normalization of serum calcium no influence on renal responsiveness was observed. Responses of maximum tubular re-absorption of phosphate were lowest in the group of hypercalcaemic patients with a solid tumour and in the patients with primary hyperparathyroidism compared with controls (0.11 ± 0.10 vs 0.22 ± 0.09 mmol/l and 0.09 ± vs 0.22 ± 0.09 mmol/l; P <0.025 and P <0.005, respectively). It is concluded that in hypercalcaemic patients with a solid tumour a humoral factor is present which inhibits the interaction of exogenous PTH and its renal receptors. In a subset of normocalcaemic patients with a squamous cell cancer the same circulating factor might be present.
Plasma aldosterone-plasma renin activity ratio A simple test to identify patients with primary aldosteronism
Authors: Lins Per-Eric , Adamson Ulf
Published: December 2008

Abstract. Thirty-two patients with hypertension and recurrent hypokalaemia were investigated on the suspicion of primary aldosteronism. On the basis of unsuppressible aldosterone secretion upon oral mineralocorticoid administration in 16 patients, a surgical exploration was made revealing a typical aldosteronoma in 12 of them, macronodular hyperplasia in two, micronodular hyperplasia in one, and micronodular hyperplasia together with a phaeochromocytoma in one patient. The remaining 16 patients with normal aldosterone suppressibility were considered to have primary hypertension. The discriminatory power of various biochemical tests related to the renin-angiotensin-aldosterone axis was analyzed in retrospect. The only parameter allowing a separation of patients with biochemically and surgically confirmed primary aldosteronism from the other group was the plasma aldosterone-plasma renin activity ratio. The present study therefore confirms the diagnostic value of this ratio for identifying patients with primary aldosteronism.
Initiation and control of ovulation in the mouse luteal phases. Effects of gonadotropins and gonadotropin releasing hormone
Authors: Gidley-Baird A. A. , White B. M. , Hau J. , Poulsen O. M.
Published: December 2008

Abstract. The aim of the present study was to examine the induction of ovulation during pregnancy, pseudopregnancy, and suckling-delayed pregnancy in mice using exogenous gonadotropins. The present results demonstrate that there are mature follicles in the ovary which can be induced to ovulate with administration of either exogenous human chorionic gonadotropin (hCG) or luteinizing hormone (LH) during pregnancy (Days 1–12) and pseudopregnancy (Days 4–8) in the mouse. hCG was relatively ineffective in initiating ovulation during suckling-delayed pregnancy, and hCG could not induce ovulation on Days 3–6 in any animals, suggesting that follicular growth is not continuous during suckling-delayed pregnancy in the mouse. Ovulation occurred in pregnant and pseudopregnant mice following injection of gonadotropin releasing hormone (GnRH) in a gelatin delay vehicle. Injection of GnRH in saline did not initiate ovulation in pregnant or pseudopregnant mice. A large release of LH was shown to occur following injection of GnRH in gelatin, but no release occurred after the same dose of GnRH in saline. In conclusion, the experiments demonstrate the existence of mature follicles during murine pregnancy and pseudopregnancy, and the lack of inductable follicles during suckling-delayed pregnancy.
Initiation and control of ovulation in the mouse luteal phases. Effects of oestrogen, progesterone and prolactin
Authors: Gidley-Baird A. A. , White B. M. , Hau J. , Poulsen O. M.
Published: December 2008

Abstract. The aim of the present study was to examine the effect of exogenous oestrogen and progesterone on ovulation in early pregnant mice and at the end of pseudopregnancy. The results demonstrate that there are mature follicles during early pregnancy which were induced to ovulate by administration of large doses of oestrogen (≥ 10 μg) on day 4 of pregnancy. Ovulation was also induced by inhibition of progesterone secretion with bromocriptine. If progesterone or prolactin was given in conjunction with bromocriptine, the ovulation effect was abolished. At the end of pseudopregnancy, the spontaneous ovulation was inhibited by injections of progesterone (1.0 mg). Oestrogen given by itself at the end of pseudopregnancy caused the animals to mate earlier than the control animals. This confirms the presence of mature follicles in mice during pregnancy and suggests that the LH peak needed for ovulation can either be provoked by administration of oestrogen or by blocking of progesterone.
Gonadotropin responses to low dose pulsatile administration of GnRH in a case of anosmia with hypogonadotropic hypogonadism associated with gonadal dysgenesis 47 XXY
Authors: Hazard J. , Rozenberg I. , Perlemuter L. , Kestenbaum S. , Vendrely E. , Raoul O. , Fiet J. , Villete J. M.
Published: December 2008

Abstract. A 25 year old man presented hypogonadotropic hypogonadism with complete anosmia (Kallman's syndrome). His chromosomic type was 47 XXY (Klinefelter's syndrome). Clinical findings were: height 183 cm, weight 62 kg, increased length of lower limbs, P2–A2 pilosity and micropenis. Only a left testis was present (1.5–1.5 cm). Bone age was 15. Testicular biopsy showed that the signs were more related to the gonadotropic deficit than to the gonadal dysgenesis; tubular hyalinization was not observed. Plasma levels of testosterone and oestradiol were very low. Plasma gonadotropin levels were below normal ranges and did not respond to an infusion test of GnRH. GnRH was administrated iv every 90 min for 3 weeks by an auto syringe infusion pump and induced a pulsatile response of FSH and LH. Plasma levels of testosterone and oestradiol were unaffected. It may be concluded that the results of pulsatile injection of GnRH confirmed in this patient a unique association of Kallmann's syndrome with complete 47 XXY Klinefelter's syndrome.
Changes in blood glucose, liver glycogen, ketone bodies and plasma insulin in suckling rats treated with a single high cortisol dose one day after birth
Authors: Aránguez M. I. , Goya L. , Pascual-Leone A. M.
Published: December 2008

Abstract. Rats treated with cortisol, 0.5 mg one day after birth, show a decrease in body and organ weight and a decrease in pituitary TSH and GH when compared to controls together with a lack of response of TSH to TRH. These alterations have been previously found in animals treated with large doses of thyroxine, neo-T4 syndrome, in both populations a brain under-development has been observed. Plasma insulin in cortisol-treated animals was higher (P < 0.01) than in the controls at 8 and 12 days of life and lower at 22 days (P < 0.001). Plasma ketone bodies were increased significantly at 8 but not at 12 and 22 days of life in the cortisol treated animals. Liver glycogen was higher than in controls at 2, 4, 6 days of life and lower at 8, 12 and 22 days. Blood glucose was higher than in controls at 2, 4 days and lower at 6, 8, 12 and 22 days of life. The timing of metabolic events is important for the adaptation and development of the post-natal animal. The perturbances in carbohydrate metabolism in suckling rats were also previously found in neo-T4 rats during the period when the brain growth spurt and energy need are the greatest; but in the rats treated with cortisol the timing of the alterations was different. This different timing of the metabolic perturbances could correlate with a different maturation in cerebral tissue found in histological studies in the two populations.
Growth hormone response to growth hormone-releasing hormone in normal and uraemic children. Comparison with hypoglycaemia following insulin administration
Authors: Bessarione D. , Perfumo F. , Giusti M. , Ginevri F. , Mazzocchi G. , Gusmano R. , Giordano G.
Published: December 2008

Abstract. The uraemic syndrome is characterized by several endocrinological disturbances. This study was undertaken in order to evaluate the GH response to growth hormone-releasing hormone (GRH) in children with chronic renal failure (CRF) and to compare the results with those observed after insulin hypoglycaemia. Twenty-two children with CRF, 10 undergoing continuous ambulatory peritoneal dialysis (CAPD) and 12 on conservative treatment (CT), age ranges 2–15 years, were studied and the data were compared with those from 14 children with normal renal function and normal hormonal behaviour, affected by short stature (NC), and those form 13 healthy adult volunteers (NA). The GRH test (1 μg/kg body weight, iv) was carried out in 8 CAPD, 8 CT, 9 NC and 10 NA subjects. The blood samples were taken every 30 min for 3 h in CAPD and CT and for 2 h in NC and NA starting at 09.00 h. The following hormones were measured: GH, LH, FSH, Prl, TSH and cortisol (F). The insulin test (0.1 U/kg body weight, iv) was carried out in 5 CAPD, 5 CT, 10 NC and 9 NA on blood samples taken every 30 min for 2 h, measuring GH and glycaemia. No adverse effects were observed after the infusion of GRH.

GRH administration induced a prompt response in all subjects, but GH plasma levels were significantly higher in uraemic children than in adults (peak value of 43.5 ± 8.2, 45.0 ± 8.4, 27.8 ± 6.0; 13.5 ± 2.6 μg/ml in CAPD, CT, NC and NA, respectively). The secretory areas were significantly narrower in NC (P < 0.05) and NA (P < 0.01) than in CAPD, and in NA than in CT (P < 0.01). The GH response to insulin did not differ in the 4 groups. The secretory area in CAPD and CT was wider after GRH than after insulin. The GH peak value of CAPD and NC was significantly higher after GRH than following insulin. No significant variation in TSH, LH and FSH was observed after the infusion of the neuropeptide, whereas Prl and F showed a reduction. The behaviour of Prl and F in NA and NC was similar after placebo and GRH.

Our data show: a) There is a greater response of GH to GRH in children than in adults; b) compared with the insulin test, GRH stimulation seems to be a reliable means of evaluating GH secretion both in normal and uraemic children owing to the absence of qualitatively different responses and to the freedom from the adverse effects or risks which follow insulin infusion; c) GRH administration does not induce any significant variation on other hypophyseal hormones and the reduction of Prl and F seems to follow the normal sleep-wake and circadian behaviour.
Circulating forms of human foetal somatomedin
Authors: Carlsson-Skwirut Christine , Andersson Charlotte , Sara Vicki R.
Published: December 2008

Abstract. Two forms of somatomedin, which cross-react in a radioreceptorassay using foetal brain membranes as matrix, have been partially purified from the serum of human foetuses aged 16–28 weeks of gestation. The purification scheme consisted of acid precipitation, Sephadex G-50 chromatography, affinity chromatography and cation exchange fast protein liquid chromatography. The two peaks of activity had apparent molecular weights of approximately 7000 and different isoelectric points. The elution positions of these peaks corresponded to the elution positions of the truncated IGF-1 variant and intact IGF-2, respectively.
Long-term effects of ACTH combined with angiotensin II on steroidogenesis and adrenal zona glomerulosa morphology in the rat
Authors: Riondel Anne M. , Rebuffat Piera , Mazzochi Giuseppina , Nussdorfer Gastone G. , Gaillard Rolf C. , Bockhorn Liliane , Nussberger Jürg , Vallotton Michel B. , Muller Alex F.
Published: December 2008

Abstract. To test the hypothesis that the trophic action of angiotensin II on the adrenal zona glomerulosa may allow a sustained stimulation of aldosterone by ACTH by preventing the morphological changes of the zona glomerulosa cells into zona fasciculata-like elements we investigated the effects in rats of a 6-day treatment with ACTH (100 μg/kg/day) alone or combined with angiotensin II (300 ng/kg/day) on corticosterone and aldosterone production and adrenal morphology. The responsiveness of both steroids to an acute ACTH dose was also studied on the last day of long-term treatment. Morphologic data showed that prolonged ACTH treatment stimulated the growth of zona glomerulosa cells, though it transformed the tubulo-lamellar cristae of mitochondria into a homogeneous population of vesicles. Angiotensin II furthered the trophic effects of ACTH but prevented the mitochondrial transformation. Despite its ability to conserve the well differentiated aspect of the zona glomerulosa cells, the administration of angiotensin II was unable to prevent the fall in the secretion of aldosterone caused by chronic ACTH treatment and its subsequent unresponsiveness to ACTH stimulation.
Insulin-like growth factor I and II in 14 animal species and man as determined by three radioligand assays and two bioassays
Authors: Zangger Ines , Zapf Jürgen , Froesch E. Rudolf
Published: December 2008

Abstract. Insulin-like growth factor I and II (IGF I and II) were determined by five different assays in human serum, in the sera of ten mammalian species and in chicken, turtle, and frog serum. Sera of all tested mammals contain two different IGFs corresponding to human immunoreactive IGF I and receptor reactive IGF II. Receptor reactive IGF II of most animal species does not show significant cross-reactivity in the RIA for human IGF II. IGF activity was also detected in sera of non-mammals, such as chicken and turtles, but not in frog serum. The IGF values obtained with the different assay system corresponded rather well: there is a good correlation between the values obtained in the protein binding and the fat cell assay, and between the results of the latter assays and the sum of immunoreactive IGF I and receptor reactive IGF II. The results suggest that those regions in the IGF I and II molecules which are responsible for reactivity with the type I IGF and the insulin receptor have not essentially changed during evolution. Similarly, the C-region, which mainly determines the immunological properties of IGFs, appears to have remained relatively constant in the IGF I, but not in the IGF II molecule.
cAMP-dependent ACTH secretagogues facilitate corticotropin releasing activity of angiotensin II on rat anterior pituitary cells in vitro
Authors: Schoenenberg P. , Gaillard R. C. , Kehrer P. , Muller A. F.
Published: December 2008

Abstract. Both arginine vasopressin (AVP) and angiotensin II (All) potentiate the corticotropin-releasing activity of CRF41 via a potentiation of CRF41-induced cAMP production. In perfused rat anterior pituitary cells, AII (10−8 mol) showed a transitory 2-fold increase in its ACTH-releasing activity, when tested after application extract of rat stalk median eminence. In order to determine whether this facilitating effect on All corticotropin-releasing activity occurred through cAMP-dependent mechanisms, the ACTH-releasing activity of All was tested after stimulation with CRF41, AVP or forskolin, three secretagogues with known effects on cAMP production. When given 16 min after CRF41, 10 μg/l, All (10−8 mol) showed a significant increase (210%) in its ACTH-releasing activity, which returned to the normal level when All-stimulation was repeated at 32 min (121%) and 48 min (100%). Similarly, forskolin, 3 × 10−6 mol, produced a significant transitory increase (208%) in the subsequent All-induced ACTH release whereas AVP, 10 μg/l and 100 μg/l, had no effect on the following ACTH response to All. These results suggest that the All-induced ACTH secretion – which is cAMP independent – nevertheless may be modulated by previously stimulation of the cAMP pathway.
The role of androstenedione and testosterone in the reproduction and antler growth of a male white-tailed deer
Authors: Bubenik G. A. , Pomerantz D. K. , Schams D. , Smith P. S.
Published: December 2008

Abstract. Seasonal levels of androstenedione and testosterone were investigated in plasma of mature intact and castrated male white-tailed deer. In four intact bucks, androstenedione concentrations were low in February and March (around 1 nmol/l) and then increased significantly (P < 0.05) from April to November (peak 2.34 nmol/l). Testosterone remained low (below 3.5 nmol/l) from February to August and then rose significantly (P < 0.01) till November (peak 36.78 nmol/l). Both hormones declined from November to February. In three castrates, androstenedione levels remained virtually unchanged (averaging around 0.5 nmol/l) between January and September. After a rapid significant increase (P < 0.05) till November (peak value 2.45 nmol/l), androstenedione concentrations declined quickly to a baseline level. Testosterone in castrates remained around 0.3 to 0.7 nmol/l for most of the year with a non-significant peak (1.45 nmol/l) in October.

These data indicate that the spring and summer increase in androstenedione in the intact deer is of testicular origin; the fall peak, however, may be a result of increased production in the adrenal glands.

It can be speculated that the increase in androstenedione in the blood of the male deer during the spring may be responsible for the seasonal initiation and support of antler growth as well as being supportive to the re-activation of the reproductive system.
A study of hypothalamic-pituitary-adrenal suppression following curative surgery for Cushing's syndrome due to adrenal adenoma
Authors: Gordon D. , Semple C. G. , Beastall G. H. , Thomson J. A.
Published: December 2008

Abstract. The hypothalamic-pituitary-adrenal axis was investigated in all six patients requiring glucocorticoid replacement 2.5–11 years after unilateral adrenalectomy for adrenal adenomas causing Cushing's syndrome. The hypothalamic-pituitary-adrenal axis was assessed by insulin induced hypoglycaemia and CRF testing in each patient. Two patients showed normal cortisol and ACTH responses to hypoglycaemia. Two patients showed subnormal cortisol responses to hypoglycaemia in the presence of high or normal basal ACTH concentrations. ACTH concentrations increased with both hypoglycaemia and CRF. Two patients showed subnormal cortisol responses to hypoglycaemia and CRF. One of these patients showed an ACTH rise following hypoglycaemia but not CRF. Defects at either hypothalamic-pituitary or adrenal levels were demonstrated and recovery of the axis appears to commence at the hypothalamic-pituitary level.
LRH agonist buserelin as a post-partum contraceptive: lack of biological activity of buserelin in breast milk
Authors: Dewart P. J. , McNeilly A. S. , Smith S. K. , Sandow J. , Hillier S. G. , Fraser H. M.
Published: December 2008

Abstract. To evaluate the possibility of using the LRH agonist buserelin as a contraceptive for lactating women we have investigated the passage of buserelin into breast milk and explored possible biological activity in the infant. Eleven mothers received 600 μg buserelin by nasal spray. Buserelin was measured by radioimmunoassay in the breast milk of these mothers, and values ranged from undetectable levels (less than 15 pg/ml) to 8800 pg/ml. The maximum amount of buserelin that an infant could ingest during an average feed would be 1–2 μg. In adult men ingestion of 600 μg buserelin dissolved in cows milk was without biological effect upon both serum and urinary levels of luteinizing hormone. There was no change in the levels of LH found in the urine of infants fed by women who had received 600 μg buserelin by nasal spray. We conclude that the small amount of buserelin passing into the breast milk of these volunteers was without biological activity when ingested by the infant.