bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum thymidine activity and insulin-like growth factors in the neonatal period
Authors: Schimpff Rose-Marie , Bozzola Mauro , Zapf Jurgen , Repellin Anne-Marie , Einschenk I.
Published: December 2008

Abstract. Growth-promoting activity measured as [3H] thymidine incorporation into lectin-activated lymphocytes was determined simultaneously with radioimmunoassayable IGF I and IGF II in cord and capillary blood collected from human neonates 30 min and 24 h after birth. All the parameters studied in cord blood were lower than in normal adults. During the early postnatal period, IGF I decreased and IGF II remained unchanged, but thymidine activity increased above the normal adult level. The differences between the values found in cord blood and in capillary blood collected within the first ½ h after birth agree with a production of growth factors by the infant. All these growth factors may play a role in foetal growth, as suggested by their correlation with birth weight. Finally, factors other than IGFs contributing to thymidine activity may play a role in neonatal growth since they are higher in newborns than in adults.
Time dependency and reversibility of the effects of exclusive cyproterone acetate therapy on pituitary adrenal function in hirsute women
Authors: Salvador J. , Barbería J.J. , Martí J. , Forga L. , Saavedra J. , Moncada E.
Published: December 2008

Abstract. The effects of cyproterone acetate (CA) administration on the pituitary-adrenal axis were studied in 30 hirsute females. The patients were treated continuously with a daily dose of 100 mg of CA for a maximal period of 12 months. Insulin-induced hypoglycaemia and ACTH infusion were performed on pre-treatment conditions and after 1, 4, 6 and 12 months of CA treatment. From a clinical point of view, a dramatic improvement of hirsutism was evident after 6 months of therapy. The most commonly reported side effects were amenorrhoea and transient uterine haemorrhage. Apart from asthenia, no symptoms of adrenal insufficiency were noticed. No changes in pituitary-adrenal secretion were observed during the first 4 months of therapy. From the 6th month, a reduction in basal as well as stimulated cortisol levels was seen. Simultaneously, an enhanced ACTH response to hypoglycaemia was observed. Both effects became more pronounced after 1 year of treatment. There were no significant changes in ACTH basal values. Six months after discontinuation of the drug, adrenocortical reserve improved but was still slightly reduced when compared to pre-treatment range at that time. These findings suggest a time-dependent negative effect of CA on adrenal steroidogenesis which shows a reversible character 6 months after antiandrogen withdrawal. Therefore, steroid cover should be considered for intercurrent illness in patients treated for longer than 6 months with this therapeutic regime.
The effect of naloxone on ATCH and β-endorphin in patients with Cushing's disease
Authors: Baranowska B. , Dorobek W. , Misiorowski W. , Jeske W. , Abdel-Fattah M. H.
Published: December 2008

Abstract. Endogenous opiates may be important in the control of ACTH secretion in men. The effect of opiate receptor blockade by naloxone on ACTH, β-endorphin-like substance and cortisol release was studied in healthy women and in 9 patients with Cushing's disease.

In the healthy subjects, ACTH, β-endorphin and cortisol levels were increased in response to naloxone. However, in 3 our of the 9 patients with Cushing's disease, a paradoxical decrease in serum ACTH, cortisol and β-endorphin concentrations was observed after naloxone administration. In the patients with a paradoxical response to naloxone, transsphenoidal microadenomectomy was ineffective.
Effects of bromocriptine on hormone production and cell growth in cultured rat pituitary cells
Authors: Johansen P. W. , Haug E. , Gautvik K. M.
Published: December 2008

Abstract. Rat pituitary adenoma cells (GH3) that spontaneously synthesize and secrete both prolactin (Prl) and growth hormone (GH) were used in this study. Bromocriptine (5 × 10−5 mol/l), a dopamine (DA) agonist, induced a rapid reduction in Prl and GH secretion with maximum effect (approximately 60%) after 15 min of treatment. Bromocriptine also inhibited Prl and GH production in a time- and dose-dependent manner with ED50 at 4 × 10−6 mol/l and 7 × 10−6 mol/l, respectively. Maximum effect was obtained at 5 × 10−5 mol/l of bromocriptine which after 24 h of treatment reduced the production of Prl and GH by ∼ 70 and ∼ 50%, respectively. After 9 days of treatment both Prl and GH production was reduced by more than 95%. Bromocriptine also reduced cellular growth rate. The ED50 was ∼ 1 × 10−5 mol/l and the maximum effect (> 50%) was observed at 5 × 10−5 mol/l. All effects of bromocriptine were reversible upon cessation of treatment. The anti-proliferative effect of bromocriptine was also observed using a rat hepatoma cell line (MH1C1) and a human epithelial cell line (HE), suggesting a non-receptor mediated growth inhibition at high concentrations of the drug.

In conclusion, the inhibitory effect of bromocriptine on secretion and production of both Prl and GH in GH3 cells occurs at a lower concentration than its effect on cell proliferation. The pharmacological effects of bromocriptine in vivo on Prl and GH producing adenomas may be explained by an action directly at the pituitary level.
Renal sodium retention and vasopressin induced kaliuresis in ethanol anaesthetised rats
Authors: Musabayane C. T. , Brimble M.J. , Balment R.J.
Published: December 2008

Abstract. Renal electrolyte excretion has been examined in water loaded ethanol anaesthetised rats receiving continuous iv saline (0.077 m NaCl) infusion. These animals exhibited very low rates of Na+, K+ and Cl− excretion by comparison with Inactin anaesthetised rats. Water loaded Inactin anaesthetised rats also showed a degree of Na retention but both Na+ and K+ excretory rates were higher than in ethanol anaesthetised animals. Plasma aldosterone levels did not differ between ethanol and Inactin anaesthetised groups.

Vasopressin administration did not effect Na+ but potentiated K+ excretion in ethanol anaesthetised animals. This contrasted with the potent natriuretic and weak kaliuretic action of vasopressin in water loaded Inactin anaesthetised rats. The significance of abnormal renal electrolyte handling and the marked kaliuretic effect of vasopressin to the use of ethanol anaesthetised animals for vasopressin bioassay is discussed.
Rapid depletion of somatostatin in isolated mouse pancreatic islets after treatment with cysteamine
Authors: Petersson Birger , Hellerström Claes
Published: December 2008

Abstract. Cysteamine (CSH; β-mercaptoethylamine) is known to deplete pancreatic somatostatin without affecting the insulin or glucagon content. It may therefore be useful for studies of intra-islet regulation of hormone release. In the present study injection of CSH (60 mg/kg body weight) to mice decreased the somatostatin content of their isolated pancreatic islets to 50% in 1 h and 30% in 4 h as compared to islets of non-injected controls. Exposure of isolated mouse islets to CSH (100 μg/ml) for either 0.5 h followed by incubation in control medium for 3.5 h, or continuously for 4 h, decreased the somatostatin content to about 40% of the controls. There was no change in the islet content of insulin or glucagon. Islets pretreated with CSH (100 μg/ml) for 1 h in vitro showed a decreased glucose stimulation of both oxygen consumption and glucose oxidation. Measurements of insulin release after a similar preincubation of the islets indicated an increased basal release and an attenuated glucose stimulation. It is concluded that CSH rapidly decreases islet somatostatin both in vivo and in vitro. This depletion may lead to a loss of tonic inhibition by islet somatostatin on basal insulin release. It is, however, more plausible that the increased basal insulin release reflected a direct effect of CSH on the islet β-cells.
Activation of adrenal adenyl cyclase by anti-thyroid plasma membrane antibodies
Authors: Ong M. , Malkin D. G. , Malkin A.
Published: December 2008

Abstract. We have previously shown that IgG isolated from rabbit anti-bovine thyroid plasma membrane (anti-BTPM) antiserum exhibits properties similar to thyroid stimulating antibodies (TSAb) in that it activates thyroid adenyl cyclase. In this study, the organ non-specificity of this reaction was investigated. It was observed that anti-BTPM IgG stimulated not only adenyl cyclase of bovine thyroid but also that of the adrenal. The stimulatory activities on the thyroid and adrenal adenyl cyclase were abolished by absorption of the IgG with bovine adrenal plasma membrane (BAPM). These results indicate that anti-BTPM antibodies, similar to TSAb, exert both thyroidal and extra-thyroidal effects. Thus anti-BTPM antibodies may be directed against antigenic determinants that are common to both thyroid and adrenal plasma membranes.

Like the anti-BTPM IgG, anti-BAPM IgG also activated both thyroid and adrenal adenyl cyclase. However, when IgG of the anti-BAPM antiserum was absorbed with thyroid plasma membranes, only the thyroid, but not the adrenal stimulating activity was abolished. It was concluded that the anti-BAPM antiserum contained antibodies directed against membrane antigens specific for the adrenal as well as common antigens shared by the thyroid.
Release of immunoreactive oxytocin and neurophysin I by cultured luteinizing bovine granulosa cells
Authors: Geenen V. , Legros J.J. , Hazée-Hagelstein M.T. , Louis-Kohn F. , Lecomte-Yerna M.J. , Demoulin A. , Franchimont P.
Published: December 2008

Abstract. We investigated the production of oxytocin (OT) and oxytocin-neurophysin (bNpI) by bovine granulosa cells cultured in presence of 10% foetal calf serum, a condition known to induce spontaneous luteinization of these cells. The production of immunoreactive OT was significantly higher in the cultures of granulosa cells harvested from large follicles than in those derived from small follicles. Chromatography on Sephadex G-25 showed similar elution sites of ovarian and synthetic OT, while high performance liquid chromatography revealed two peaks of OT-immunoreactivity, one of which (± 65% of the total immunoreactivity) coincided with synthetic OT. In another experiment, we could observe a gradual increase of OT, bNp I and progesterone production by granulosa cells derived from large follicles, in relation with the incubation time. The mean molar ratio OT: bNp I was 2.2 ± 0.5 (sem), and we found a significant positive correlation between the production of OT and bNp I (r = 0.77; P < 0.01) and between the production of OT and progesterone (r = 0.80; P < 0.01). Furthermore, the cellular OT and bNp I content of large follicles-derived granulosa cells before culture was 4–5 times lower than the total amount of OT and bNp I produced during a 72-h incubation, suggesting an active synthesis of these peptides. thesis as observed in the hypothalamo-neurohypophysial system and that the granulosa productions of OT, bNp I and progesterone are closely related.
Endocrine effects of high-dose ketoconazole therapy in advanced prostatic cancer
Authors: Heyns W. , Drochmans A. , van der Schueren E. , Verhoeven G.
Published: December 2008

Abstract. The endocrine effects of ketoconazole (400 mg orally every 8 h) were studied in 9 previously untreated patients with advanced prostatic cancer. Five of these patients were followed for 12 months. A rapid fall in the serum concentration of testosterone was noted in all patients studied. Minimal values were observed on day 4 of treatment but thereafter serum testosterone increased slowly. The effect of the drug on unbound testosterone was relatively more important, since sex hormone binding globulin increased markedly during treatment. An increase in progesterone and LH was observed in all patients. This suggests that ketoconazole limits the conversion of C21-precursors into androgens. This block is compensated in part by activation of the hypothalamo-hypophyseal feedback system. Urinary 17-ketosteroids were decreased but 17-hydroxysteroids were unaffected by the treatment. In 5 patients followed monthly over a period of 12 months the mean testosterone concentration ranged from 69 ng/100 ml in one patient to 428 ng/100 ml in another. An excellent inverse correlation could be demonstrated between the mean serum concentration of testosterone and the mean concentration of ketoconazole. The change of serum dehydroepiandrosterone sulphate also correlated inversely with the mean ketoconazole level. Increased concentrations of oestradiol were noted in 2 patients with slight gynaecomastia. It is concluded that long-term suppression of androgen production can be realized by high-dose ketoconazole treatment and that the degree of suppression is proportional to the serum levels of the drug.
Effects of bromocriptine on cell cycle distribution and cell morphology in cultured rat pituitary adenoma cells
Authors: Johansen P. W. , Clausen O. P. F. , Haug E. , Fossum S. , Gautvik K. M.
Published: December 2008

Abstract. The effects of bromocriptine, a dopamine (DA) agonist, on cell cycle distribution and cell morphology have been studied in a clonal strain of rat pituitary adenoma cells (GH3) which produce and secrete spontaneously both prolactin (Prl) and growth hormone (GH). DNA flow cytometry showed that bromocriptine caused a dose-dependent delay in cell cycle traverse concomitantly with a reduction in cellular growth rate. The lowest concentration of bromocriptine (5 × 10−6 mol/l) significantly (P < 0.05) increased the relative number of cells in the S phase and reduced the proportion of cells in the G1 phase. At higher concentrations (1 × 10−5–5 × 10−5 mol/l) bromocriptine delayed cell cycle traverse through effects on cells in the S, G1 and G2 phases. These effects occurred already after 24 h of treatment. These results were supported by autoradiography of nuclear uptake of [3H]thymidine and by measurements of the number of cells arrested in metaphase after colcemide treatment (mitotic rate).

Bromocriptine at 5 × 10−5 mol/l altered profoundly GH3 cell structure inducing cell clustering and typical changes in mitochondrial and nuclear ultrastructures.

Since Prl and GH production is a characteristic of cells in G1 phase, the inhibitory effect of the lowest antiproliferative concentration of bromocriptine (5 × 10−6 mol/l) can only partly be explained by alterations in phase distribution. At the highest concentration of bromocriptine (5 × 10−5 mol/l) hormone production and cell division are also inhibited due to general toxic effects as reflected by the ultrastructural changes.
Regulation of vasopressin secretion in a patient with chronic hypernatraemia
Authors: Smitz Simon , Legros Jean-Jacques
Published: December 2008

Abstract. A patient with the chronic hypernatraemia syndrome is described. Using a sensitive and specific radioimmunoassay, the plasma arginine-vasopressin (AVP) level was measured under various conditions.

With an unrestricted diet, the plasma AVP level was inappropriately low for the degree of plasma hyperosmolality (0.9 pmol/l and 302 mOsm/kg, respectively).

After chronic water loading, plasma osmolality was 271 mOsm/kg, plasma AVP level 1.5 pmol/l, and the urine remained hypertonic with respect to the plasma.

During hypertonic saline infusion, plasma osmolality increased from 271 to 294 mOsm/kg without a concomitant increase in the plasma AVP concentration. After sc injection of apomorphine and after haemodynamic stimulation, the plasma AVP concentration increased from 0.8 to 36 pmol/l and from 1.2 to 6.3 pmol/I, respectively. These data demonstrate a selective deficiency in the osmoregulation of the AVP secretion. The observed neuroendocrine abnormalities may be linked to a congenital malformation of the brain.
Hyperthyroidism caused by a pituitary thyrotrophin-secreting tumour with excessive secretion of thyrotrophin-releasing hormone and subsequently followed by Graves' disease in a middle-aged woman
Authors: Kamoi Kyuzi , Mitsuma Terunori , Sato Hiroshi , Yokoyama Motoharu , Washiyama Kazuo , Tanaka Rhuichi , Arai Okuhiro , Takasu Nobuyuki , Yamada Takashi
Published: December 2008

Abstract. A 46-year-old woman had signs of thyrotoxicosis and galactorrhoea. Serum immunoreactive TSH and its α-subunit increased in the presence of high serum triiodothyronine (T3), thyroxine (T4), and free T4 concentrations, whereas β-subunit TSH was undetectable. Exogenous TRH failed to increase serum TSH. Serum TSH was markedly suppressed by glucocorticoid, but was increased by antithyroid drug. l-Dopa or bromocriptine partially suppressed, but nomifensine had no influence on serum TSH.

Serum prolactin (Prl) was above normal and markedly increased by TRH, but depressed by bromocriptine and not suppressed by nomifensine. Plasma TRH was normal in the hyperthyroid state, but was increased by glucocorticoid and antithyroid drug. Excess thyroid hormone depressed plasma TRH concentrations. Basal serum GH levels were constantly low. Transsphenoidal removal of the tumour normalized serum hormones (T3, T4 free T4, TSH, α-subunit and Prl), and eradicated the clinical signs of hyperthyroidism and galactorrhoea. Histological study of the tumour tissue demonstrated both thyrotrophes and somatotrophes. A reciprocal relationship between serum TSH and T4 concentrations shifted to a higher level before but was normalized after removal of the tumour. Ten months later, the clinical signs of thyrotoxicosis and the increase in serum thyroid hormone recurred without a concomitant increase in serum TSH and its α-subunit. Thyroidal auto-antibodies were slightly positive, but thyrotrophin-binding inhibitor immunoglobulin (TBII) was negative. Administration of antithyroid drug produced a euthyroid state, but 3 years later, discontinuation of the treatment resulted in recurrent hyperthyroidism without suppressed plasma TRH and with no evidence of regrowth of the pituitary tumour.

It is suggested that the patient initially had hyperthyroidism owing to excessive TSH secretion from the tumour caused by abnormal TRH secretion, and subsequently had hyperthyroidism owing to Graves' disease.
Secretion and metabolic clearance rates of thyroxine and triiodothyronine in streptozotocin-diabetic rats
Authors: Jolin Trinidad , Ortiz-Caro Javier , González Margarita
Published: December 2008

Abstract. This study was undertaken to evaluate the effects of streptozotocin-induced diabetes on T4 and T3 production rate (PR) and metabolism in rats. [125I]T4 and [125I]T3 were injected iv and sequential blood samples were obtained. Plasma ethanol extracts were analyzed for [125I]T4 and [125I]T3 by thin layer chromatography. T4 and T3 production rates and kinetic parameters of T4 and T3 metabolism in control, diabetic and insulintreated diabetic rats were assessed by applying kinetic analyses to measurements of disappearance of injected T4 and T3 radiotracer from plasma. The metabolic clearance rate (MCR) and the fractional disappearance rate (K) of T4 in diabetic rats (0.72 ± sd, 0.02 ml/h · 100 g, and 0.034 ± 0.006 h−1, respectively) were significantly lower (P 0.001) than in the control group (1.01 ± 0.04 ml/h · 100 g and 0.056 ± 0.004 h−1). Similarly, the MCR and K values of T3 were also significantly reduced (P < 0.001) in the diabetic animals: 16.2 ± 0.7 ml/h · 100 g and 0.088 ± 0.007 h−1 in controls vs 13.0 ± 1.2 ml/h · 100 g and 0.058 ± 0.009 h−1 in diabetics, respectively. Insulin therapy significantly reversed these alterations. There was also a significant reduction (P < 0.001) in plasma T4 (18 ± 6 ng/ml) and T3 (0.20 ± 0.05 ng/ml) concentrations in the diabetic rats compared to control values, whose T4 and T3 levels averaged 65 ± 10 and 0.68 ± 0.09 ng/ml, respectively. In addition, the T4 and T3 production rates in diabetic rats (12.9 ± 5.6 and 2.6 ± 0.2 ng/ml · 100 g, respectively) were significantly different (P < 0.001) from control values (65.6 ± 10 and 11.0 ± 0.7 ng/ml · 100 g). In conclusion, the dramatic fall in plasma T4 and T3 concentrations associated with diabetes appear to be the result of the reduction in the PRs rather than to changes in MCRs.
The effects of forskolin and LH on cAMP changes and maturation in the follicle-enclosed oocytes of hamsters
Authors: Hubbard C.J.
Published: December 2008

Abstract. Graafian follicles from mature pro-oestrous hamsters were incubated with LH, various concentrations of forskolin, or forskolin plus LH. The incubations were either terminated at different time periods for analysis of follicular or oocyte cAMP levels or incubated for the entire 6 h and the oocytes examined to determine maturational status. Incubations with LH (1 μg/ml) produced a short transient rise in follicular and oocyte cAMP concentrations, while forskolin (60 μm, 20 μm and 10 μm) produced cAMP values which remained elevated for longer periods of time. The 1 μm concentration of forskolin initiated oocyte maturation (28%) but at a level which was significantly below that stimulated by LH (74%). When LH was included with forskolin, a dramatic rise in follicular cAMP occurred which was approximately 2 times greater than levels seen with LH alone. A significant percentage of oocytes matured when 100 nm forskolin (45%) was included with LH (I μg/ml) but not with any other concentration of forskolin tested. Maturation percentages for follicle-enclosed oocytes exposed to 1 μm forskolin plus 1 μ/ml of LH (3.8%) were not different from the controls (7%). However, when 1 μm forskolin was combined with 100 ng/ml of LH a significant percentage of oocytes matured (47%). While continuous incubations with forskolin did not stimulate a high percentage of oocytes to mature, oocytes from follicles exposed to forskolin (60 μm and 20 μm) for short periods (5 min–30 min) with a change to plain medium did mature.

The results of these studies indicate that, in the hamster, long term exposure to forskolin inhibits maturation in follicle-enclosed oocytes. This appears to be the result of persistently elevated cAMP levels in both the follicle and the oocyte. By contrast, short-term incubations initiate maturation. In these groups, cAMP presumably undergoes a transient increase similar to that which is initiated by LH. Maturation in the follicle-enclosed oocytes of hamsters appears to require both a rise and decline in cAMP.
Assay of adenosine in human adipose tissue
Authors: Ranta Susanna , Kiviluoto Tuula , Newby Andrew C. , Ohisalo Jorma J.
Published: December 2008

Abstract. A method is described to assay the adenosine content of human adipose tissue. Tissue pieces of 10–20 mg were frozen within 1 sec of excision by a conchotome. The pieces were pooled and ground in liquid nitrogen, divided into samples weighing 50–100 mg each and placed in perchloric acid. Neutralized defatted extracts were treated by Dowex AG-1 to remove nucleotides and lyophilized. The adenosine content was measured by RIA using antiserum raised against laevulinic acid (02',3'-adenosine-acetal)-albumin conjugate. The adenosine content in human abdominal sc adipose tissue was 0.56 ± 0.08 nmol/g of tissue (mean ± sem). This shows that adenosine is present in human adipose tissue at concentrations that have been shown to have regulatory effects on cAMP accumulation and lipolysis.
Lack of plasma prolactin response to intravenously injected vasoactive intestinal polypeptide in patients with prolactin-secreting adenoma
Authors: Kaji Hidesuke , Chihara Kazuo , Kita Tetsuya , Kashio Yoichi , Okimura Yasuhiko , Fujita Takuo
Published: December 2008

Abstract. The effect of an iv bolus injection of 1 μg/kg body weight of vasoactive intestinal polypeptide (VIP) on plasma prolactin (Prl) levels was tested in 13 normal volunteers and 15 patients with hyperprolactinaemia of various aetiology: 9 with Prl-producing pituitary tumours (6 prolactinoma, 3 mixed pituitary adenoma, secreting Prl and growth hormone (GH)), 6 with hyperprolactinaemia secondary to a hypothalamic lesion (4 craniopharyngioma, 1 hypothalamic germinoma, 1 meningoencephalitis). In the normal subjects, an iv injection of VIP caused a prompt increase in plasma Prl with peaks 2- to 3-fold greater than the basal values. On the other hand, none of the 9 patients with a Prl producing pituitary tumour showed any obvious Prl rise after VIP irrespective of a marked difference in their basal Prl levels. Lack of a Prl response to VIP was also found in the 2 patients with hypothalamic lesions (1 craniopharyngioma, 1 hypothalamic germinoma) whose basal Prl concentration was higher than 100 ng/ml. However, in the remaining 4 patients with hypothalamic lesions whose basal Prl concentration was less than 100 ng/ml, VIP injection resulted in a stimulation of the Prl secretion with a maximal net increment of 11.3 ± 3.8 ng/ml, which is not different statistically form that (16.3 ± 3.3 ng/ml) in the normal subjects, but significantly higher than that (−2.3 ± 2.7 ng/ml) in the 4 patients with Prl-secreting adenoma and a basal Prl concentration of less than 100 ng/ml. These results indicate that the VIP test may be a useful diagnostic tool for discriminating a Prl-producing tumour from a hypothalamic lesion in patients with mild hyperprolactinaemia.
The bioavailability of thyroxine and 3,5,3′-triiodothyronine in normal subjects and in hyper- and hypothyroid patients
Authors: Hasselström Kjeld , Siersbæk-Nielsen Kaj , Lumholtz lb Bo , Faber Jens , Kirkegaard Carsten , Friis Thorkild
Published: December 2008

Abstract. A new method for the estimation of the bioavailability of thyroxine (T4) and 3,5,3′-triiodothyronine (T3) is described based on gel separation followed by antibody extraction of labelled T4 and T3 from serum, and using the area under the curve of disappearance of the tracer (AUC) for the calculations. The peak serum concentrations of radioactive labelled T4 and T3 were reached approximately 90 min after oral administration of both tracers. The relative difference of duplicate estimations was below 10% (n = 3). The bioavailability of T4 in 6 euthyroid controls was in median 65% (range 64–75%), and it was significantly increased both in hyperthyroidism (88% (75–99%), n = 6, P < 0.01) and hypothyroidism (84% (67–100%), n = 6, P<0.02).

The bioavailability of T3 in 6 euthyroid controls was in median 78% (69–99%) and significantly greater than that of T4 (P < 0.02). The bioavailability was unaffected by hyperthyroidism (79% (61–98%), n = 9) and hypothyroidism (77% (66–97%), n = 7). No significant difference between T4 and T3 bioavailabilities was found in hyper- or hypothyroidism.

The clinical implication of the present study is that the bioavailability of T4 and T3 is almost identical and approximately 80% in patients with severe hypothyroidism.
Homeorhesis during early lactation. Euthyroid sick-like syndrome in lactating cows
Authors: Aceves C. , Ruiz-J. A. , Romero C. , Valverde-R. C.
Published: December 2008

Abstract. Serum levels of thyroxine (T4), triiodothyronine (T3) and reverse T3 (rT3) were studied in dry, early (first trimester) and middle (second trimester) lactating purebred Holstein cows. The study encompassed three different seasons: autumn, winter and spring. Under comfortable weather conditions (temperature 22°C; relative humidity, 40%) or moderately hot (28°C; 60%), January and October, respectively, cows in early lactation exhibited significantly lower levels of T4 and T3, and higher values of rT3 than dry or middle lactating animals. In contrast, during May, when environmental temperature increased (34°C; 40%), a clear-cut shift in T3/rT3ratio occurred, and animals in early lactation exhibited the highest T3 and the lowest rT3 concentrations.

These findings suggest that in dairy cattle, peripheral thyroid hormone metabolism plays a major role in regulating the homeorhetic responses involved in the maintenance of high priority functions.
Ablation of serotonergic nerves in the rat pancreas. Lack of effects on hormone secretion and intrinsic blood flow
Authors: Jansson Leif , Leung Pearl E. , McEvoy Robert C.
Published: December 2008

Abstract. The aim of the present study was to evaluate the physiological role of intrapancreatic serotonergic nerves for endocrine pancreatic function.

The specific uptake of [3H]5-hydroxytryptamine (5-HT) into pancreatic slices from the rat was completely abolished after an intrapancreatic injection of 5,7-di-hydroxytryptamine (5,7-DHT). Since also high-affinity uptake of [3H]5-HT was absent it was concluded that intrapancreatic serotonergic nerves were destroyed.

The effects of this selective denervation on glucose-stimulated insulin and somatostatin secretion were investigated with the aid of perfused rat pancreatic glands removed 3, 7 or 14 days after the injection of 5,7-DHT. Neither the basal release of these hormones nor their response to a glucose challenge was significantly altered by the ablation of the intrapancreatic serotonergic nerves.

The microsphere technique was used to investigate the blood flow through the pancreatic islets in rats injected intrapencreatically with 5,7-DHT 4 days previously. No significant changes in either the whole pancreatic blood flow or the islet blood flow could be demonstrated.

These result show that in normal physiological conditions the intrapancreatic serotonergic nerves do not affect the hormonal release from or the blood flow through the endocrine pancreas.
Male pseudohermaphroditism due to 3β-hydroxysteroid dehydrogenase-isomerase deficiency associated with atrial septal defect
Authors: Perrone L. , Criscuolo T. , Sinisi A. A. , Graziani M. , Manzo T. , Sicuranza R. , Bellastella A. , Faggiano M.
Published: December 2008

Abstract. Male pseudohermaphroditism in a 6 month old boy, due to congenital 3β-hydroxysteroid dehydrogenase deficiency, associated with atrial septal defect, is reported. At 2 weeks he required therapy for severe dehydration and projectile vomiting. The parents were first cousins and one female sibling had died suddenly at 2 months. The patient presented with melanoderma, perineal hypospadias with testicles in a bifid scrotum and atrial septal defect (ostium secundum). Complete cytogenetic studies showed a 46,XY karyotype. Serum sodium ranged from 129 to 140 mEq/l and serum potassium from 5.1 to 4.6 mEq/l. Basal plasma hormonal studies showed normal androstenedione (Δ4A), decreased cortisol (F), slightly elevated ACTH, 17-hydroxy-progesterone (17-OH-P) and testosterone (T), and highly increased dehydroepiandrosterone-sulphate (DHEA-S) levels. ACTH stimulation increased and DXM suppression decreased the plasma levels of DHEA-S, 17-OH-P and T but not that of F; hCG stimulation during cortisone therapy did not change the levels of DHEA-S and T. Corticosteroid therapy normalized electrolyte levels and reduced melanoderma and hormonal hypersecretion. Moderately elevated plasma levels of 17-OH-P and T suggest a partial testicular 3β-HSD deficiency. The multifactorial inheritance and the relatively high prevalence of atrial septal defect vs the rarity of adrenal enzymatic defect suggest a causal association even if a common genetic factor cannot be excluded.
Changes in circadian rhythm and suppression of the plasma cortisol level after prolonged stress in the sheep
Authors: Przekop F. , Stupnicka E. , Wolińska-Witort E. , Mateusiak K. , Sadowski B. , Domański E.
Published: December 2008

Abstract. Diurnal variations in the plasma cortisol level were studied in anoestrous, pro-oestrous and pregnant ewes subjected to weak electric stimulation of the forelimbs 9 h daily for 3 consecutive days. In non-pregnant ewes the cortisol level rose on each of the 3 days when the stimulation was applied and then decreased on the day following the stimulation. A similar decrease in plasma cortisol concentrations in pregnant ewes appeared on the second day of footshocking. The acrophase of the circadian rhythm on electrostimulation days was synchronous with the time of application of footshocks; therefore, in stimulated ewes it was significantly accelerated compared to the prestimulatory day. A decrease in the plasma cortisol level in pro-oestrous and pregnant ewes was accompanied by disappearance of its normal rhythmicity. Since a normal plasma cortisol response to exogenous corticotrophin was noted after 3 days of foot-shocking it seems unlikely that the decrease in the cortisol level after prolonged stress was caused by exhaustion of the adrenal cortex. Some central mechanisms which could account for the biphasic changes in the plasma cortisol level and for disturbances of the hormone diurnal rhythmicity under conditions of prolonged stress are discussed.
Autoradiographic binding studies with [3H]oestradiol and [3H]dihydrotestosterone in the autonomic genital ganglion (plexus of Frankenhäuser) of the mouse
Authors: Schleicher G. , Stumpf W. E. , Thiedemann K.-U. , Drews U.
Published: December 2008

Abstract. Male, female and Tfm mice (testicular feminization) were injected with [3H]oestradiol or [3H]dihydrotestosterone, and autoradiograms prepared of male accessory sex organs and of the cervico-vaginal portion of the female reproductive tract.

After injection of [3H]oestradiol in male, female and Tfm animals a nuclear concentration of radioactivity was found in a subpopulation – about 20–30% – of the neurons of the genital ganglion. No such concentration was seen after [3H]dihydrotestosterone. The results suggest a direct genomic effect of oestradiol on certain neurons of the autonomic genital ganglion in both sexes.
Congenital hypothyroidism in a Turkish family: the role of immunoglobulins blocking the trophic effects of TSH and maternal-foetal relationship
Authors: van der Gaag R. D. , Frisch H. , Weissel M. , Wick G. , Drexhage H. A.
Published: December 2008

Abstract. A Turkish family with frequent intermarriages is described, in which two siblings were born with persistent forms of congenital hypothyroidism, in the elder child concomitant with absent radioactive thyroid imaging. The mother was clinically euthyroid throughout the period of observation, but showed in addition to thyroid microsomal antibodies, high levels of immunoglobulins blocking the trophic action of TSH. These maternal growth blocking antibodies were transiently present in the youngest of the siblings (from birth to 2 months of age). She had a relatively mild form of congenital hypothyroidism (T3: 33 μg/100 ml; T4: 3.9 μg/100 ml). The older sibling, with proven non-functioning thyroid tissue (negative thyroidscan, T4: 0.4 μg/100 ml) produced the growth-blocking immunoglobulins herself and may thus represent a juvenile form of thyroid autoimmunity with a very early onset.

An aunt and uncle of the children, both hypothyroid since birth, were at the age of 19 and 18 years weakly positive for growth blocking immunoglobulins.

This study indicates that familial forms of congenital hypothyroidism are probably complex and may be brought about by maternal to foetal passage of thyroid reactive autoantibodies, but also by the inheritance of a trait for thyroid autoimmunity. In some cases these two mechanisms might act in conjunction.
Evaluation of sodium and potassium pump activity and number in diabetic erythrocytes
Authors: Nagamatsu Shinya , Inoue Nobuo , Murakawa Shoichiro , Matsui Hideo
Published: December 2008

Abstract. The Na+,K+-ATPase (= Na pump), which produces the concentration gradient of Na+ and K+ across the cell membrane, was studied in diabetic erythrocytes. The activity and number of Na pumps, which are functional and quantitative expression of the Na+, K+-ATPase in erythrocytes, were measured by ouabainsensitive 42K or 43K influx and by [3H]ouabain binding, respectively. The turnover rate of the pumps was calculated from the two measurements to evaluate in situ activity of the pump.

The Na pump activity was found to be higher in the diabetic (193 ± 12 nmol K+/h · 109 cells) than in the normal group (164 ± 6) (P < 0.05), though the affinities of the pump for extracellular K+ were not different. The number of Na pumps and the Kd of the pumps for ouabain in the diabetic group were not significantly different from those in the normal group (354 ± 12 site/cell and 4.33 ± 0.20 nm). The turnover rate of the diabetic group tended to be higher than that of the normal group. The rate was about one third of the molecular activity reported for Na+,K+-ATPase under optimum conditions. These results indicate that the enzymatic properties as well as the number of Na pumps were not altered in diabetic erythrocytes despite the increased Na pump activity. Therefore the increased activity of the erythrocyte Na pump in diabetes mellitus suggests an increase of cation permeability associated with a possible disorder in the diabetic membrane.
The human corpus luteum secretes 5α-pregnane-3,20-dione
Authors: Bäckström Torbjörn , Andersson Agneta , Baird David T. , Selstam Gunnar
Published: December 2008

Abstract. A radioimmunoassay for 5α-pregnane-3,20-dione (5α-DHP) in plasma is described. The concentration of 5α-DHP in peripheral plasma during the follicular phase of the menstrual cycle was of the same order of magnitude as that of progesterone (P). During the luteal phase, the plasma 5α-DHP was 8-fold higher than in the follicular phase and about 1/3 of the P concentration. The concentration of 5α-DHP in ovarian venous plasma draining an ovary containing the corpus luteum was 22-fold higher than the concentration in plasma from the contralateral ovarian vein. These results show that the corpus luteum secretes significant amounts of 5α-DHP.
Concentrations of immunoreactive tonin in submandibular glands and saliva of the rat
Authors: Hirata Yukio , Tomita Masahiro , Fujita Takuo , Ikeda Masao
Published: December 2008

Abstract. The submandibular gland (SMG) of the rat contains tonin, an enzyme of serine proteases, which specifically cleaves angiotensinogen and angiotensin I to yield angiotensin II directly. Using a specific RIA for rat tonin, the present study was performed to examine the concentrations of immunoreactive (IR) tonin in SMG of normal Wistar male rats with various ages, those in SMG and saliva of normal adult males and females, and also its SMG levels of castrated males and testosterone-treated females.

The concentrations of IR-tonin in SMG of immature 4 week old male rats were very low but rose exponentially with increasing age to reach adult levels (3–6 μg/mg wet tissue) in male rats after 6 week old or more. SMG of the adult male rat contained 10-fold more IR-tonin than that of the female rat and male saliva contained 5-fold more IR-tonin than that of females. The concentrations of SMG IR-tonin in the castrated males fell to about one-tenth the levels of normal males, whereas SMG IR-tonin levels in the testosterone-treated females increased about ten times more than those of normal females.

These data confirm the sexual dimorphism of rat SMG with respect to the concentrations of tonin and indicate that androgens play an important role in regulating the synthesis and/or storage of tonin in rat SMG. It is also suggested that tonin is secreted into saliva in concentrations reflecting its SMG levels. However, biological significance of tonin in SMG and saliva remains obscure.
Factitious Cushing's syndrome
Authors: O'Hare J. P. , Vale J. A. , Wood S. , Corrall R. J. M.
Published: December 2008

Abstract. In this report we describe a patient who produced the clinical and laboratory features of Cushing's syndrome by injecting himself for many months with hydrocortisone. Factitious Cushing's syndrome is a variant of the Münchausen syndrome and should be considered if tests used to establish the diagnosis of Cushing's syndrome appear incongruous particularly in subjects with access to medical intelligence and drugs.
Cushing's disease presenting with severe osteoporosis
Authors: Petersen Palle , Jacobsen Svend Erik Hove
Published: December 2008

Abstract. Cushing's disease is usually associated with a variety of symptoms and signs making a characteristic clinical picture. A patient with Cushing's disease due to a pituitary adenoma in whom the only striking feature was osteoporosis is presented. In addition, unusually severe hypopituitarism, was present.
Clomiphene citrate induces pituitary GnRH receptors in ovariectomized rats: its possible role in induction of ovulation
Authors: Shimizu Ikuya , Terakawa Naoki , Aono Toshihiro , Tanizawa Osamu , Matsumoto Keishi
Published: December 2008

Abstract. Since our previous studies have shown that clomiphene citrate (clomiphene) acts directly on the pituitary gland and exerts a facilitatory role on oestradiol-17β (E2)-induced LH surge in chronically ovariectomized rats, the effect of clomiphene on pituitary GnRH receptors was investigated. A single ip injection of either 5 μg E2 or 200 μg clomiphene did not induce LH release in adult rats ovariectomized 1–2 weeks before the injection. However, a significant increase in serum LH was noted 24 h after a single injection of E2 in the ovariectomized rats, if clomiphene was pre-injected 48 h before the E2 injection. The content of pituitary GnRH receptors in the ovariectomized rats (62 ± 9 fmol/pituitary) remained almost unchanged until 24 h after a single injection of clomiphene but significantly increased 48 h after the injection (105 ± 13 fmol/pituitary) without any alterations in the affinity for GnRH. To determine steroid specificity for the increase in pituitary GnRH receptors, other classes of steroids were injected in the ovariectomized rats. A single dose of E2 increased GnRH receptors, but either progesterone or 5α-dihydrotestosterone failed to show any effect on the level of GnRH receptors. These results suggest that clomiphene may augment oestrogen-induced pre-ovulatory LH surge in anovulatory women, at least in part by increasing the number of pituitary GnRH receptors.
Release of thyroid hormone from circulating thyroglobulin in the rat
Authors: Taura Michiko , Izumi Motomori , Nagataki Shigenobu
Published: December 2008

Abstract. Under normal conditions, a small amount of thyroglobulin (Tg) exists in peripheral blood. However, the fate of circulating Tg is unclear. In the present study, in vivo labelled rat Tg was injected iv into rats whose thyroids had been blocked with KI to determine whether circulating Tg released thyroid hormone by hydrolysis in extrathvroidal tissues. Radiolabelled Tg was obtained from thyroid of rats injected with 125I 24 h before sacrifice, and subsequently purified by ammonium sulphate precipitation. The plasma samples were obtained from tail veins or by cardiac punctures at various times following injection of [125I]rat Tg. The radioactive samples were separated into iodoprotein, iodoaminoacid and iodide fractions using columns of anion and cation exchange resins. The per cent radioactivity of the iodoprotein, iodoaminoacid an iodide fractions, respectively, was 91.2, 3.8 and 5.2 at 15 min and 66.9, 17.4 and 15.4 at 20 h after injection. In the iodoaminoacid fractions, the presence of T4, T3, MIT and DIT was defined by further fractionation using a Sephadex G-25 column. At 20 h after injection, more than 75% of the radioactivity of the iodoaminoacid fraction was found to be incorporated in T4 and T3. It is concluded that circulating Tg is hydrolyzed in extrathyroidal tissues and that thyroid hormone is released into the circulation, but the amounts of T4 and T3 released are not physiologically significant.
Sex-dependent effect of streptozotocin-induced diabetes mellitus on hepatic steroid metabolism in the rat
Authors: Skett Paul
Published: December 2008

Abstract. Diabetes mellitus is known to affect drug and steroid metabolism in the rat liver. Recently it has been shown that the effect on drug metabolism is both transient and sex-dependent. This study shows that the effect of diabetes on steroid metabolism is also sex-dependent i.e. only seen in the male and the effect is always to abolish the sex differences in steroid metabolism found in the intact animals. 7α-hydroxylase activity, which is higher in the female, is increased by diabetes in the male whereas 6β-hydroxylase, 16α-hydroxylase and 17-oxosteroid reductase, which are all higher in the male, are decreased by diabetes. This is a very similar result to that found for drug metabolism and indicates that insulin plays a role in the maintenance of sex differences in hepatic steroid metabolism in the rat as it does for drug metabolism.
Effect of gonadotrophin-releasing hormone analogue (GnRH-A) administration on serum gonadotrophin and steroid levels in patients with polycystic ovarian disease
Authors: Mongioi Alessandro , Maugeri Grazia , Macchi Maria , Calogero Aldo , Vicari Enzo , Coniglione Francesca , Aliffi Antonia , Sipione Costantino , D'Agata Rosario
Published: December 2008

Abstract. A gonadotrophin-releasing hormone (GnRH) analogue, D-Ser[TBU]LRH-EA10, (GnRH-A), at a dose of 200 μg was given daily for 2 months to 6 women with polycystic ovarian disease (PCO). Prior to therapy the patients presented elevated LH, testosterone (T), oestrone (E1) and dihydrotestosterone (DHT) in the circulation. In response to GnRH-A, these subjects exhibited a marked decrease in circulating T, DHT and androstenedione (A) levels as measured 24 h after GnRH-A injection, by 4 weeks and onwards (P < 0.05). After 2 weeks of daily administration, the serum LH profile, evaluated by sampling at 2, 4. 7 and 24 h after injection of GnRH-A, was not different from baseline, whereas after 4, 6 and 8 weeks the levels were significantly lower (*P < 0.01). The profile of serum T levels was unmodified at the second week, but significantly decreased thereafter (*P <0.01). At the end of treatment, the E1 concentrations, elevated in pre-injection condition, were markedly decreased.

These data demonstrate that in PCO subjects, GnRH-A significantly lowered the elevated levels of androgens commonly found in these patients. The close correlation observed between reduced serum LH and androgen concentrations suggests that pituitary desensitization could be responsible for the reduction in androgen levels, and may be evidence for a gonadotrophin dependence of the elevated concentrations of T in these patients.
Mechanisms by which 5HT stimulates ovulation in the immature rat treated with pregnant mare serum gonadotrophin
Authors: Wilson C. A. , McNeilly A. S. , Yeo T.
Published: December 2008

Abstract. Pregnant mare serum gonadotrophin (PMS) normally induces a pre-ovulatory immunoreactive LH surge followed by ovulation in 27 day old rats provided they weigh more than 60 g; ovulation does not occur in the lighter rats although a pre-ovulatory LH surge can still be measured. 5HT injected into the paraventricular nucleus (PVN) can induce ovulation in these smaller rats treated with PMS and does so without appearing to stimulate extra immunoreactive LH. The LH secreted in the under 60 g PMS-treated rats is a pleiomorphic form since it cannot be detected by cytochemical bioassay, indicating abnormal biological activity, which may account for its failure to induce ovulation. After unilateral injection of 5HT into PVN, the LH was detectable by the bioassay. Injection of 5HT also stimulated the release of growth hormone and prolactin but had no significant effect on the plasma concentration of the gonadotrophins or corticosterone. Since an injection of exogenous GH converted the LH to a fully bioactive form it is suggested that GH is important in inducing the secretion of an 'adult' form of LH in the peripubertal rat necessary for first ovulation and that 5HT exerts its ovulatory effect via stimulating the release of this hormone.
Metoclopramide test in the diagnosis of isolated hypogonadotrophic hypogonadism
Authors: Dunkel Leo
Published: December 2008

Abstract. The responses of serum prolactin (Prl) to metoclopramide and LH and FSH to GnRH were studied simultaneously in 9 boys with hypogonadotrophic hypogonadism (HH), 7 boys with constitutional delay of puberty (D) and 15 controls. Metoclopramide increased the Prl levels in all groups. The boys with HH had lower Prl responses than the controls, whereas the boys with D had similar responses to the controls. Of the 9 boys with HH, 8 had subnormal Prl responses, 3 subnormal LH and none subnormal FSH. A metoclopramide test is clearly more sensitive than a GnRH test in differentiating HH and D and appears to make the differentiation between these two conditions clearer.