bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF IODIDE ON THE ADENYL CYCLASE SYSTEM OF THE MOUSE THYROID IN VIVO
Authors: Saddok C. , Gafni M. , Gross J.
Published: December 2008

Iodide, administered to mice either acutely or chronically, depressed the thyroidal cyclic adenosine monophosphate (cAMP) response to 20 mU bovine TSH. When iodide was administered acutely there was a 60% reduction in the cAMP accumulation after 100 μg, or 1 μg KI given to mice on normal iodine diet (NID), or low iodine diet (LID), respectively. When iodide was administered chronically by supplementing the LID with graded doses of KI for 11 days, the cAMP response to TSH was found to be inversely related to the dietary iodine. Inhibition occurred after 5 μg KI, a dose similar to the daily iodine intake. Iodide depressed, but did not abolish, the thyroidal cAMP response to TSH.

Iodide had no effect on phosphodiesterase activity, whereas thyroidal adenyl cyclase activity was diminished by the prior administration of 100 μg KI. The iodide effect was abolished by pre-treatment with methylmercaptoimidazole i.e. the inhibition is related to iodide oxidation. The newly organified thyroidal iodine (NOTI), formed at 2 h from 0.1–1000 μg KI was determined. The amount of NOTI was highly correlated to the degree of inhibition, irrespective of the iodine content of the diet. This relationship was continuous up to 100 ng NOTI and 70% inhibition, which are the maximal values obtained for NOTI formation and inhibition of cAMP accumulation. These plateau levels were reached with 100 or 1 μg KI in mice on NID or LID, respectively. These results indicate that the inhibitor is an iodinated substance whose intrathyroidal formation is quantitatively parallel to, or a part of NOTI.
EFFECTS OF ALPHA-ADRENERGIC STIMULATION AND BLOCKADE ON PLASMA PARATHYROID HORMONE CONCENTRATIONS IN COWS
Authors: Blum J. W. , Guillebeau A. , Binswanger U. , Kunz P. , Da Prada M. , Fischer J. A.
Published: December 2008

Experiments were designed to investigate responses of immunoreactive parathyroid hormone (PTH) during alpha-adrenergic stimulation and blockade in cows. Alpha-adrenergic agonists (methoxamine, phenylephrine and noradrenaline, the beta-adrenergic action of which was blocked by propranolol) did not change PTH and free fatty acid levels, whereas they characteristically increased the blood pressure and decreased the heart rate. In contrast, alpha-adrenergic blockade by phentolamine progressively increased PTH levels. The elevated PTH concentrations, associated with increased plasma noradrenaline and free fatty acid levels, rising heart rate and decreasing blood pressure, indicated that all these changes can be related to a beta-adrenergic stimulatory mechanism. Beta-adrenergic stimulation was presumably responsible for the initial elevation of PTH concentrations, whereas, during the later phase of the phentolamine infusions, a concomitant hypocalcaemia probably also produced a stimulatory effect.
ACUTE INFLUENCE OF LH AND FSH ON CYCLIC AMP FORMATION IN ISOLATED GRANULOSA CELLS OF THE RAT
Authors: Hamberger Lars , Nordenström Knut , Rosberg Sten , Sjögren Anita
Published: December 2008

A technique for the mechanical isolation of granulosa cells from the rat ovary is described. Cyclic AMP formation by the isolated granulosa cells of the follicles in various stages of development was studied in response to the administration in vitro of gonadotrophins. In granulosa cells from small to medium-sized follicles FSH but not LH stimulated cAMP formation, while in cells from pre-ovulatory follicles both gonadotrophins had a stimulatory effect. The effects of both gonadotrophins were transient with a maximal response after 15 to 60 min of incubation. In the presence of the phosphodiesterase inhibitor, 3-isobutyl-methylxanthine, the action of FSH was potentiated and prolonged while the response to LH was unaffected. These data indicate that both gonadotrophins activate the adenylate cyclase system of the isolated granulosa cells while FSH in addition stimulates the phosphodiesterase activity.

Consecutive determinations of cAMP during and after the pre-ovulatory LH-FSH surge, demonstrated a rise of cAMP levels in granulosa cells from the pre-ovulatory follicles following endogenous gonadotrophin release. cAMP levels remained high or increased until the time of ovulation.
EFFECT OF TWO PROGESTINS ON HUMAN ENDOMETRIAL ENZYMES AND TRACE ELEMENTS
Authors: Jelínek J. , Jelínková Marta , Hagenfeldt Kerstin , Landgren Britt-Marie , Diczfalusy E.
Published: December 2008

Seven healthy normally menstruating women were treated with 50 μg ethinyl oestradiol from day 4 to day 12 of the menstrual cycle (control cycle). In another two cycles either 2.5 mg norethisterone2) or 4 mg megestrol acetate3) was added on days 11 and 12. In all 3 cycles an endometrial biopsy was taken on day 13.

Extractable protein, DNA, eight enzymes and five trace elements were determined in the endometrial specimens. Part of every biopsy was evaluated histologically.

Addition of megestrol acetate for 2 days to ethinyl oestradiol caused a significant increase in endometrial isocitrate dehydrogenase (ICDH) and alkaline phosphatase (AP) activities. Norethisterone induced similar changes.

Neither of the two progestins caused any significant changes in the endometrial content of Cu, Zn, Mn, Na or K.

Norethisterone induced early or clear signs of secretory activity in the endometrium of four subjects out of seven. For megestrol acetate this ratio was five out of seven.

It is suggested that changes in the activity of some endometrial enzymes, especially of ICDH, can be used for an early detection of progestational effect of compounds on the endometrium; these changes may be more sensitive than the morphological evaluation.
CHANGES IN CYCLIC NUCLEOTIDES OF RAT THYROID BY CHRONIC ADMINISTRATION OF LATS AND TSH
Authors: Ochi Yukio , Hosoda Shiro , Hachiya Takashi , Kajita Yoshihiro , Yoshimura Manabu , Miyazaki Tadayoshi
Published: December 2008

The effects of LATS and TSH on the cyclic nucleotide content and enzymatic activity in rat thyroid was observed during the continuous administration of LATS or TSH for 6 days. Serum T4 and T3 levels were increased significantly compared with the saline controls. The cyclic nucleotide (cAMP and cGMP) levels and enzyme activities per wet weight of tissue were determined.

The thyroid weight in both the LATS and TSH groups increased approximately two-fold, but cAMP and cGMP content per wet weight did not significantly change. Neither cyclic nucleotide showed any significant change in plasma.

The cAMP-PDE activity in the thyroid significantly increased in both the LATS and TSH groups, but the cGMP-PDE activity was unchanged. Neither was cyclic nucleotide-PDE activity changed in the plasma.

The ATPase activity in the thyroid increased markedly in both the LATS and TSH groups, while 5′-nucleotidase activity did not change.

These data suggest that LATS and TSH appear to have a stimulatory effect on the metabolism of cAMP, but do not affect the metabolism of cGMP.
SERUM SOMATOMEDIN ACTIVITY MEASURED AS SULPHATION FACTOR IN PERIPHERAL, HEPATIC AND RENAL VEINS OF PATIENTS WITH ALCOHOLIC CIRRHOSIS
Authors: Schimpff R. M. , Lebrec D. , Donnadieu M. , Repellin A. M.
Published: December 2008

Serum somatomedin (SM) activity, measured as sulphation factor on chick embryo cartilage, and growth hormone (GH) levels were measured in peripheral, hepatic and renal veins of 23 patients with alcoholic cirrhosis. SM activity (mean ± sem) was 0.65 ± 0.05 U/ml in peripheral vein, 0.59 ± 0.04 U/ml in hepatic vein, and 0.74 ± 0.07 U/ml in renal vein. Mean GH levels were respectively 2.8, 2.5 and 3.1 ng/ml. Compared to peripheral vein, SM increase in renal vein was 19% (P < 0.05). Serum SM activity was significantly lower in 13 patients with alcoholic hepatitis associated with cirrhosis than in other 10 patients (P < 0.02 in hepatic blood and P < 0.05 in peripheral blood). The decrease of SM activity seems related to cytolysis and hepato-cellular insufficiency. At last, in patients with alcoholic hepatitis, SM activity was lower in the hepatic vein than in the peripheral vein (P < 0.05). The cause of this difference remains under discussion, no SM inhibitors being found in the serum samples used in this study.
EFFECT OF GRADED ORAL DOSES OF OESTRADIOL ON CIRCULATING HORMONAL LEVELS
Authors: Dada O. A. , Laumas V. , Landgren B.-M. , Cekan S. Z. , Diczfalusy E.
Published: December 2008

A single oral dose of micronized oestradiol (1, 2 or 4 mg) was administered to 10 normally menstruating women on the second day of 3 consecutive menstrual cycles. The order in which the 3 doses were given was chosen randomly for each subject. Samples of peripheral blood were withdrawn on 3 occasions (10, 5 and 1 min) before and on 9 occasions (0.37, 0.75, 1.5, 3.0, 6.0, 12.0, 24.0, 48.0 and 72.0 h) after the ingestion of oestradiol. Oestradiol, oestrone, oestradiol sulphate, oestrone sulphate, testosterone and LH were measured by means of radioimmunoassays in blood plasma on all occasions.

The levels of all oestrogens increased significantly following the ingestion of oestradiol, although to a greatly different extent. The largest and most prolonged increase was seen in the case of oestrone sulphate, the levels of which — depending on the dose ingested — were 20–50 times higher than the pre-treatment levels 3 h after the ingestion of the oestradiol capsule. The increase of the levels of oestrone sulphate was still significant (P < 0.001) after 24 h, and following the ingestion of 2 and 4 mg of oestradiol even after 72 h (P < 0.05). The levels of oestrone and oestradiol sulphate exhibited smaller increases 3 h after ingestion, i. e. 4–10 and 2.5–5 times, respectively, and the plasma levels of oestradiol showed a minor increase only (1.4–1.8 times).

The concentration of oestradiol metabolites studied increased proportionally with the dose of oestradiol administered. On the other hand, a clear-cut dose — effect relationship could not be observed between the amount of oestradiol administered and the plasma levels of LH and testosterone.

The data indicate that the bulk of perorally administered oestradiol is transformed to oestrone sulphate accompanied by smaller quantities of oestrone and oestradiol sulphate and that the ratios of circulating oestrogens seen after the ingestion of oestradiol deviate considerably from those observed in the normal menstrual cycle.
THE DETERMINATION OF 5α-ANDROSTANE-3α,17β-DIOL IN HUMAN PLASMA BY RADIOIMMUNOASSAY
Authors: Laband P. , Tresguerres J. A. F. , Lisboa B. P. , Volkwein U. , Tamm J.
Published: December 2008

Antibodies have been raised in rabbits against 3α,17β-dihydroxy-5α-androstane-6-0-carboxymethyloxime coupled with Cohn's fraction IV-4. The antiserum exhibited significant cross reactions with 5β-androstane-3α,17β-diol, 5α-dihydrotestosterone, and testosterone. No cross reactions were observed with 5α-androstane-3β,17β-diol and 5-androstene-3β,17β-diol. The methodological criteria for the measurement of 5α-androstane-3α,17β-diol in human plasma were as follows: The specificity was ensured by separating the cross reacting steroids by thin layer chromatography. The intraassay and interassay coefficients of variation were found to be 6.2 and 10.2 %, respectively. The sensitivity was 30 pg. The recovery of different amounts of 5α-androstane-3α,17β-diol added to human plasma (80, 120, and 200 pg) yielded 91.3, 92.5, and 93.5%, respectively. The following concentrations of 5α-androstane-3α,17β-diol have been determined in human plasma (mean ± sd, ng/dl): Normal males: 18.98 ± 5.9; normal females: 2.65 ± 0.27; females with idiopathic hirsutism: 11.9 ± 6.4; pre-pubertal children: not detectable.
BIOCHEMICAL STUDIES ON THE IODINE ORGANIFICATION DEFECT OF PENDRED'S SYNDROME
Authors: Niepomniszcze Hugo , Coleoni Aldo H. , Degrossi Osvaldo J. , Scavini Luis M. , Curutchet H. Pablo
Published: December 2008

Biochemical studies were performed on the thyroid of a typical case of Pendred's syndrome who underwent total thyroidectomy. The patient, a euthyroid 14 year old female, presented congenital nerve deafness, goitre and impairment of thyroidal iodine organification.

Thyroid peroxidase (TPO) activity was quantitatively normal. Using crude preparations, enzyme activity ranged from 176–366 nmoles of I−-incorporated (inc.) to tyrosine/g of tissue. Normal values are 220–410 nmoles I− inc./g. Digitonin pseudosolubilized TPO, assayed by the tyrosine-iodinase method, showed 44.9 nmoles I− inc./mg of protein for the Pendred's tissue, and 44.5 nmoles I− inc./mg for the control glands. Soluble TPO was utilized for enzyme-kinetic studies. The Km for H2O2, obtained in the triiodide assay with iodide as hydrogen donor, was in the same order of magnitude for both Pendred's and control thyroids, being 3 × 10−4 m and 3.5 × 10−4 m, respectively. In the guaiacol assay, the Pendred's Km value of 4 × 10−4 m was also normal for H2O2. Pre-incubation of enzyme preparations with 5 × 10−5 m haematin did not stimulate TPO activity.

Thyroidal NADPH-cytochrome c reductase and monoamine oxidase activities were normal. A low concentration, 37 mg/g, of a qualitatively normal thyroglobulin was found in Pendred's goitre. The iodine content of thyroglobulin was 0.19 %.

It is concluded that the four major components of the iodination process: 1) thyroid peroxidase, 2) iodide, 3) thyroglobulin and 4) H2O2 would be normally present in Pendred's glands. It is postulated that a failure of these major components to come together at the iodination site might be the explanation of the organification defect of Pendred's syndrome.
RETARDED BIOSYNTHESIS OF THYROGLOBULIN SUBUNITS AND THEIR POLYMERIZATION IN VITRO AFTER SUPPRESSION OF TSH SECRETION IN RATS BY CHRONIC ADMINISTRATION OF EXCESS THYROXINE IN THE FORM OF IODINATED CASEIN
Authors: Sinadinović J. , Krainčanić M. , Kostić G. , Jovanović M.
Published: December 2008

The effects of short- and long-term (from 3 days to 28 weeks) administration of excess thyroxine in the form of the iodinated casein "Protamone" (0.2%) to rats on the content of soluble thyroid iodoproteins and on biosynthesis and polymerization of thyroid proteins in vitro were investigated. The concentration of soluble iodoproteins significantly increased (40–80%) up to 2 weeks of treatment, and after that remained at the same level. 27S iodoprotein markedly increased during thyroxine treatment. The content of DNA in the gland and the thyroid weight were a little lower in the treated rats than in the control.

The incorporation rate of [14C]leucine into soluble and microsome-bound proteins in vitro was markedly reduced in the treated animals (30–80 % of control). Thyroxine pre-treatment of rats induced retarded synthesis of thyroglobulin and its subunits in vitro. The inhibition of the synthesis of thyroid proteins in vitro and the incrrease in the soluble iodopritein content in the gland in vivo was not correlated with the duration of thyroxine treatment.

The immobilization of pre-formed thyroglobulin in the follicle lumen for a long time period is probably an important factor in the enlarged conversion of thyroglobulin into 27S iodoprotein.

In conclusion, the long-term suppression of endogenous TSH secretion by administration of thyroxine results in an accumulation of iodoproteins in the thyroid and a reduced rate of synthesis of iodoproteins; after 2 weeks a steady state is reached both with regard to iodoprotein accumulation and synthesis. Finally, the results obtained suggest that the thyroid-pituitary axis becomes adapted to chronic administration of excess thyroxine.
CALCITONIN ACTIVITY OF THE THYROID GLAND IN PRIMARY HYPERPARATHYROIDISM
Authors: Broulik P. D. , Hradec E. , Pacovský V.
Published: December 2008

The thyroidal content of calcitonin was investigated in patients with euthyroid goitre, patients undergoing laryngectomies or neck operations and finally patients with primary hyperparathyroidism using method of biological titration. Patients with primary hyperparathyroidism had markedly decreased content of calcitonin in the thyroid gland when compared with the content of calcitonin of both groups of patients without calcium metabolism disturbance. Decreased content of calcitonin in patients with primary hyperparathyroidism can be explained by long lasting hypercalcaemia during which the rate of biosynthesis of calcitonin in the C cells does not keep up with the rate of release of calcitonin into the circulation.
ABSENCE OF INHIBITION BY HYPERPROLACTINAEMIA ON OVARIAN RESPONSE TO EXOGENOUS GONADOTROPHIN
Authors: Aono Toshihiro , Yasuda Motoi , Shioji Takenori , Kondo Kunio , Kurachi Keiichi
Published: December 2008

In order to assess the effect of hyperprolactinaemia on the ovarian response to exogenous gonadotrophin, serum oestrogen levels were determined in 6 normal females. Two hundred and twenty-five IU of human menopausal gonadotrophin (hMG) was im injected daily for 3 days from the 4th day of the menstrual cycle, and the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and oestradiol-17β were determined by radioimmunoassay daily for 7 days starting from the first day of injection (control cycle). After 2 months the same schedule was applied to the previous 6 subjects and in addition sulpiride 100 mg bid was given orally during the course of the study (sulpiride cycle).

There was a significant increase in serum FSH and a decline in serum LH during hMG treatment in both groups. The mean (± se) serum levels of PRL in the sulpiride group increased gradually from 24.5 ± 3.8 ng/ml (1st day) to 56.2 ± 3.4 ng/ml (7th day). All these levels were significantly higher than those of the control group. The mean (± se) serum oestradiol increments by hMG stimulation in control and sulpiride groups showed a peak on the 5th day with respective levels of 757.2 ± 202.3 and 845.3 ± 263.3 pg/ml. No significant differences in the mean oestradiol increment were found between the two groups on any day.

These results indicate that acute hyperprolactinaemia does not appear to induce ovarian refractoriness to exogenous gonadotrophin in normal cyclic women.
OESTROGEN TREATMENT AND SUBSEQUENT PREGNANCY IN TWO PATIENTS WITH SEVERE HYPERGONADOTROPHIC OVARIAN FAILURE
Authors: Starup J. , Philip J. , Sele V.
Published: December 2008

This report describes in detail the histological and hormonal findings in a patient with Turner's syndrome (45,XO) and a patient with premature menopause (46,XX), who both conceived after withdrawal or reduction of substitution therapy with oestrogens. The aetiology of severe hypergonadotrophic ovarian failure is discussed, and theories regarding a possible relationship between the oestrogen treatment and subsequent pregnancy are hypothesized.
MATURATIONAL CHANGES IN SHEEP OVARIAN FOLLICLES: GONADOTROPHIC STIMULATION OF CYCLIC AMP PRODUCTION BY ISOLATED THECA AND GRANULOSA CELLS
Authors: Weiss T. J. , Armstrong D. T. , McIntosh J. E. A. , Seamark R. F.
Published: December 2008

Theca and granulosa tissues isolated from sheep ovarian follicles of different sizes were incubated in the presence of human chorionic gonadotrophin (HCG; 5 IU/ml) or follicle stimulating hormone (FSH; 5 μg NIH-FSH-S11/ml) for 40 min. Changes in the total amounts of cyclic 3′,5′-adenosine monophosphate (cAMP) were used as an index of the responsiveness of these preparations to the hormones. Thecal tissue of both large (4–6 mm in diameter) and small (1–3 mm) follicles responded similarly to gonadotrophins. Granulosa cells from small follicles failed to respond to stimulation by HCG. FSH, however, consistently increased cAMP production in comparison with controls or cells treated with HCG. Granulosa cells of large follicles responded to both HCG and FSH.
STUDIES OF SEXUAL DIFFERENTIATION OF SHEEP
Authors: Wilson P. R. , Tarttelin M. F.
Published: December 2008

Gonadotrophin releasing hormone (GnRH) (1 μg/kg was injected intravenously into pre-natally androgenised and untreated control ram and ewe lambs and castrated pre-natally androgenised rams on each of the 6th, 14th, 22nd and 30th week of post-natal life, and plasma samples collected at −20, −10, 0, 15, 30, 60, 90, 120 and 240 min from injection for LH estimation. No difference in pre-injection LH levels or responses to GnRH were observed between pre-natally androgenised and control male and female lambs. Castration resulted in significantly elevated pre-injection LH levels (P < 0.001) and responses to GnRH (P < 0.05).

Forty-five week old control and pre-natally androgenised ewes were subjected to a GnRH injection and plasma sampling routine identical to that described above both before and 2 weeks after ovariectomy. Significantly elevated pre-injection LH levels and LH responses to GnRH (P < 0.001) resulted from ovariectomy but there were no differences in either parameter between control and androgenised ewes either before or after ovariectomy.

It is concluded that since pre-natal androgenisation altered neither pituitary gonadotrophic activity nor pituitary or hypothalamic steroid negative feedback activity, the depressed basal LH secretion reported earlier in pre-natally androgenised lambs (Wilson & Tarttelin 1978) was probably due to impairment of hypothalamic production and/or release of endogenous GnRH rather than to modification of pituitary gland function.
FINE STRUCTURE OF RAT PROLACTIN CELLS AFTER TREATMENT WITH A LONG ACTING DEPOT CONTRACEPTIVE
Authors: Aumüller G. , Wagner R. , Gräf K. J.
Published: December 2008

Adult intact female rats were injected with norethisterone oenanthate (NOe), with or without simultaneous administration of CB-154, or with oestradiol benzoate (OeB). The ultrastructure of prolactin (PRL) cells due to the various treatment regimens was investigated and compared with the situation found in controls.

Both after treatment with NOe or NOe plus CB-154, the number of PRL cells increased and displayed various ultrastructure signs of stimulation. The determination of serum PRL levels coincides with these morphological findings. In all treated animals mammary gland DNA content was significantly increased.

The results presented indicate that proliferative changes in the rat mammary gland depend predominantly on the presence of progestogenic activities additionally to PRL, whereas the effect of oestrogens was regarded as an indirect effect via their PRL-stimulatory action.
POSSIBLE ROLE OF HYPERAMMONAEMIA AND/OR OF PORTOSYSTEMIC SHUNTS ON THE VARIABILITY OF THE TSH RESPONSE TO TRH IN CIRRHOTIC PATIENTS
Authors: Schlienger J. L. , Hasselmann M. , Imler M.
Published: December 2008

Serum concentrations of thyroid hormones (T3, T4) and the TSH response to TRH administered iv were measured by radioimmunoassay in 21 patients with advanced cirrhosis and compared to 20 control patients without liver disease (group A). While the mean T4 values (8.6±0.3 μg/100 ml) were similar for the two groups, the mean T3 values were significantly lower in patients with liver disease (123 ± 12 vs. 156 ± 10 ng/100 ml). The mean baseline TSH levels and the magnitude of the peak were normal but very scattered in these patients. The TSH response to TRH appeared independant of nutritional status, T4 and T3, anaemia, hypoalbuminaemia, transaminasaemia and bilirubinaemia. The TSH release after TRH injection seemed however to be markedly elevated in cirrhotic patients with hyperammonaemia. Therefore, patients with liver disease were separated into two groups according to the absence (group B; n = 11) or the presence (group C; n = 10) of hyperammonaemia. Mean T4 values and the free thyroxine index were lower in group C (7.2 ± 0.6 vs. 9 ± 0.6 μg/100 ml and 1.87 ± 0.16 vs. 2.49 ± 0.15) but mean T3 and basal TSH values did not differ in group B and C. The TSH response was slightly dispersed in B and lower than that observed in A or in C (P < 0.01). A hyperresponsiveness in 4 patients and a hyperresponsiveness in 2 other patients was noted in group C without any correlation with the basal TSH value or T3 or T4

Since hyperammonaemia has been considered as a biological parameter of hepatic encephalopathy, it is suggested that the THS release which is neuraminergic controlled may be altered by this situation resulting in a cerebral aminergic mediators depletion.
TRIIODOTHYRONINE METABOLISM IN DIABETIC RATS
Authors: Boado R. , Brown T. J. , Bromage N. R. , Matty A. J. , Zaninovich A. A.
Published: December 2008

Triiodothyronine (T3) metabolism was assessed in untreated and in insulin-treated diabetic rats and the results compared with a corresponding control group. Male rats of the Wistar strain were made diabetic by the intraperitoneal injection of alloxan in a dose of 17.5 mg/100 g body weight and thereafter maintained normoglycaemic for a week and until 24 h before initiation of the study. The average glycaemia in control and in insulin-treated animals was 135 mg/100 ml, whereas in the untreated diabetic rats it was 455 mg/100 ml. Each animal was injected a tracer dose of [125I]T3 containing 2 μCi of 125I and 15 ng of T3. Heparinized blood samples were obtained by cardiac puncture at 5, 18 and 24 h following the injection of the tracer. The excretion of inorganic 125I in the 24-h collections of urine was also determined. The kinetics of [125I]T3 were studied by the extrapolation method using the straight line of plasma disappearance between 5 and 24 h. It was found that the untreated diabetic rats had a significant slowing of plasma disappearance of labelled T3. The decrease in fractional hormone turnover was balanced by a slight expansion of the distribution space, which presumably led to a larger hormone pool and a normal degradation rate of T3. These events seemed substantiated by the normal excretion of 125I in the urine observed in untreated animals. A parallel study of plasma hormone binding using a red cell uptake method showed a significant reduction of binding avidity for T3 by plasma proteins in the untreated diabetic animals. The administration of insulin restored plasma T3 kinetics and binding avidity to normal, as observed in control rats. It was concluded that untreated diabetes mellitus induced changes in T3 kinetics and in T3 serum binding without altering hormone deiodination, parameter which reflects tissue utilization of T3.
STUDIES ON THE TISSUE-DISPOSITION AND FATE OF [14C]STREPTOZOTOCIN WITH SPECIAL REFERENCE TO THE PANCREATIC ISLETS
Authors: Johansson Eva Britt , Tjälve Hans
Published: December 2008

The tissue-disposition and fate of [14C]streptozotocin, labelled in the methyl-group of the N-nitrosomethylurea side-chain, have been studied in mice. Whole-body autoradiography, quantified by densitometric measurements, showed that the pancreatic islets had a high capacity to accumulate radioactivity after the injection of [14C]streptozotocin. Microautoradiography of the pancreas showed that centrally located cells were labelled while peripherally located cells contained a low labelling, indicating a selective labelling of the β-cells. A high radioactivity was present in the liver and the cortex of the kidney at most survival intervals. About 17 % of the radioactivity was exhaled as 14CO2 during 6 h, which shows that the methyl group of the N-nitrosomethylurea side-chain is split off. Radioactivity was shown to be incorporated in the acid-insoluble precipitate of the pancreatic islets, the liver, the kidney, and the exocrine pancreas. This may, to a varying extent, be due both to alkylating reactions and to incorporation of radioactivity in the macromolecules of the tissues via normal metabolic pathways. About 44 % of the radioactivity was excreted as unchanged [14C]streptozotocin in the urine during 24 h, while about 1 % of the radioactivity was found in the faeces. Whole-body autoradiography of [14C]streptozotocin in two Chinese hamsters and one rat also showed a high accumulation of radioactivity in the pancreatic islets in these species.
REDUCED POST-NATAL RISE OF TESTOSTERONE IN PLASMA OF CRYPTORCHID INFANTS
Authors: Gendrel Dominique , Job Jean-Claude , Roger Marc
Published: December 2008

Plasma testosterone has been studied in 31 full-term male infants born with bilaterally undescended testes (14) or unilaterally undescended testis (17). From 10 to 89 days after birth, the post-natal testosterone rise was significantly lower in the 18 infants who remained cryptorchid at 4 months than in the 13 who underwent spontaneous testicular descensus and in the normal controls. Blunted post-natal Leydig cell secretion in cryptorchids may relate to a primary LH defect and could contribute to the impairment of both testicular descensus and maturation.
A GONADOTROPHIN-RESPONSIVE VIRILIZING ADRENAL TUMOUR IDENTIFIED AS A MIXED GANGLIONEUROMA AND ADRENOCORTICAL ADENOMA
Authors: Takahashi Hisatoshi , Yoshizaki Kenichi , Kato Hideyuki , Masuda Toshihisa , Matsuka Goro , Mimura Tsuneo , Inui Yasunobu , Takeuchi Satoru , Adachi Haruo , Matsumoto Keishi
Published: December 2008

A 38-year-old gravida 2, para 1 woman, who had suffered from virilization and amenorrhoea for 8 years was examined. She had peripheral serum testosterone (T) levels of 3.9–8.7 ng/ml (normal level: 0.32 ± 0.09 ng/ml) with normal serum levels of dehydroepiandrosterone (DHA), aldosterone and cortisol (F) and normal urinary 17-ketosteroids (17-KS).

Dexamethasone (DXM 2 mg/day for 5 days) suppressed the serum F level adequately, but reduced the high T levels only slightly. The administration of commercial hCG 6000 IU for 3 days increased both the serum T levels (5.68 to 9.83 ng/ml) and the serum DHA levels (4.9 to 9.8 ng/ml, normal range 4–6 ng/ml), but synthetic ACTH-Z (Cortrosyn-Z®, 1 mg, Organon) did not affect the serum T level. The basal serum LH level was abnormally low, and constant infusion of synthetic LH-RH (200 μg/5 h) resulted in good responses of serum LH and FSH and increase in the serum T level from 5.2 to 9.1 ng/ml.

Computerized tomography, ultrasonography and pneumo-retroperitoneumroentgenography showed the presence of a large tumour in the right adrenal. The tumour was a circumscribed irregularly lobulate mass, measuring 16×8×8 cm and weighing 500 g. Histologically, it was identified as a ganglioneuroma containing numerous scattered groups of large polyhydral cells similar to adrenocortical cells, forming islets in some places. After removal of the tumour from the right adrenal, the high serum T level decreased to the normal female level in 24 h.
CHOLINERGIC INFLUENCES ON HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL ACTIVITY OF STRESSED RATS: AN APPROACH UTILIZING AGONISTS AND ANTAGONISTS
Authors: Sithichoke N. , Marotta S. F.
Published: December 2008

Cholinergic involvement in the regulation of the hypothalamic-pituitary-adrenocortical (HPA) system of male rats was evaluated using muscarinic (atropine and methacholine) and nicotine (mecamylamine and nicotine) agents, which were selected for their specificity on cholinergic receptors (ChR). They were administered either intracerebroventricularly (icv) to produce central effects, or ip to produce both central and peripheral effects, prior to subjecting the animals to either auditory or hypercapnic stress for 1 h. Plasma corticosterone was used as an index of HPA activity. The results suggest that central muscarinic ChR are involved in inhibiting HPA activity in both non-stressed and stressed animals, whereas central nicotinic ChR are excitatory during stress but inactive in the non-stressed state. Stimulation of peripheral nicotinic ChR appeared to potentiate the HPA response to hypercapnia, and to inhibit the central excitatory nicotinic ChR when the latter were activated in non-stressed and auditory stressed rats. These data suggest that during auditory stress the HPA system is more dependent upon the cholinergic system for its activation than during non-stressed and hypercapnic states.
MAINTENANCE OF SPERMATOGENESIS INDUCED BY HMG TREATMENT BY MEANS OF CONTINUOUS HCG TREATMENT IN HYPOGONADOTROPHIC MEN
Authors: Johnsen Svend G.
Published: December 2008

In a long-term hypophysectomized male HCG treatment was unable to initiate spermatogenesis. However, a spermatogenesis induced by HMG/HCG treatment could be maintained by HCG alone for 7 years with clinical fertility. In another hypogonadotrophic male HCG was also unable to initiate spermatogenesis. But a spermatogenesis once induced by HMG/HCG treatment could be maintained for more than one year with HCG alone. It is suggested that gonadotrophin treatment of the hypogonadotrophic male should consist of HMG + HCG until complete spermatogenesis is induced followed by maintenance treatment with HCG.
SECRETION OF THE ANDROGENS IN THE MALE GUINEA-PIG DURING THE PERINATAL PERIOD
Authors: Pelardy G. , Delost P.
Published: December 2008

Plasma and testicular testosterone, androstenedione and dihydrotestosterone concentrations have been estimated by radioimmunoassay in the male foetus and newborn guinea-pigs between day 62 of pregnancy to day 12 of post-natal life. The prenatal period is characterized by low plasma androgen levels and high testosterone and androstenedione testicular content. After birth there is a peak of plasma testosterone concentration on day 3 concomitant with a release of testicular androgens; no similar increase of androstenedione or DHT is observed in plasma. This peak in plasma testosterone is testis dependent because it disappears after castration; it is also light dependent at birth. The investigations on testosterone and androstenedione peripheral metabolism have shown that day 3 after parturition is a "critical period" in the evolution of the metabolic clearance rate, the production rate and the conversion rate of these two androgens. The neonatal increase in plasma testosterone may be accounted for by the variations in these metabolic parameters and may have an influence upon certain sexual target organs, especially upon the vas deferens, the androgens content of which increases during the same "critical period".
FAILURE OF THE TRH TEST TO PREDICT THE CLINICAL COURSE OF PATIENTS IN REMISSION AFTER ANTITHYROID DRUG THERAPY FOR GRAVES' DISEASE
Authors: Irvine W. J. , Gray R. S. , Toft A. D. , Seth J. , Cameron E. H. D.
Published: December 2008

In an attempt to assess the predictive value of the TRH test in patients in remission after stopping antithyroid drugs for thyrotoxicosis, 11 euthyroid patients with a subnormal (group I) and 23 euthyroid patients with a normal serum TSH response to TRH (group II) were followed-up for one year. The mean ± se intervals since the withdrawal of drug therapy were 23.2 ±1.6 and 20.4 ± 0.7 months, respectively, at the outset of the study. Five patients (45 %) from group I and 7 patients (30 %) from group II relapsed during the period of observation. In addition, a change from a subnormal to a normal serum TSH response to TRH and vice versa occurred in some patients. It is not possible to predict by means of the TRH test the subsequent clinical course of patients in remission following antithyroid drug therapy.
PRODUCTION AND CHARACTERIZATION OF ANTISERA TO SYNTHETIC 1–34 HUMAN PARATHYROID HORMONE FRAGMENTS: POSSIBLE IMPLICATIONS FOR THE CORRECTNESS OF PROPOSED STRUCTURES
Authors: Visser T. J. , Buurman C. J. , Birkenhäger J. C.
Published: December 2008

Antisera were raised to 1–34 hPTH-B and to 1–34 hPTH-N.

In the assays utilizing antisera to 1–34 hPTH-B the relative affinity of 1–84 hPTH was correlated with the activity displayed by 1–34 hPTH-N. The activity of 13–34 hPTH-B was always higher than that of 1–12 hPTH, but both peptides displaced most of the radioiodinated 1–34 hPTH-B from the antiserum. This may be due to the fact that the 1–12 and 13–34 fragments contain a homologous sequence: 6–10 (-GIN-Leu-Met-His-AsN-) and 29–33 (-GIN-Leu-Val-His-AsN-). It was possible to develop a heterologous radioimmunoassay using anti-(1–34 hPTH-B) antiserum and [125I] 1–34 hPTH-N with favourable properties: complete cross-reactivity of 1–84 hPTH and high sensitivity (< 10−14 mol/tube).

All antisera to 1–34 hPTH-N were characterized by a high reactivity towards 1–34 bPTH and a higher avidity for 1–84 hPTH than for 1–34 hPTH-B. In all assays using either antisera to 1–34 hPTH-B or antisera to 1–34 hPTH-N 19–24 hPTH-B was completely inactive.

In accordance with our previous observation that position 30 in native hPTH is probably occupied by an aspartic acid residue, the present study seems to indicate that position 28 or 30 is indeed represented incorrectly by the structure of 1–34 hPTH-B.
ACTH STIMULATES LATE STEPS IN CORTISOL BIOSYNTHESIS
Authors: McKenna Terence J. , Island Donald P. , Nicholson Wendell E. , Miller Rebecca B. , Lacroix Andre , Liddle Grant W.
Published: December 2008

Acute stimulation of steroidogenesis with ACTH produces striking elevations in the plasma levels of cortisol as well as certain cortisol precursors. However, although states of chronic ACTH excess are characterized by similar elevations in cortisol, the precursor levels are in the low normal range. We have previously proposed that chronic stimulation of adrenal steroidogenesis with ACTH may enhance the activity of the late phase of cortisol biosynthesis. Precursor steroids would then be more efficiently used with less precursor leakage from the cell and greater cortisol production. In the present study, we have examined the effect of ACTH on the late phase of cortisol biosynthesis in vitro using bovine adrenal cell suspensions. To exclude the well established effect of ACTH on early cortisol biosynthetic steps we treated the cell suspensions with aminoglutethimide. This agent inhibits the conversion of cholesterol to pregnenolone and therefore to cortisol, both under basal conditions and during treatment with ACTH. To aminoglutethimide-treated cell suspensions, we added pregnenolone, 1 7-OH-pregnenolone, progesterone, 17-OH-progesterone and 11-deoxycortisol, with and without ACTH. In the presence of ACTH, significantly more cortisol was formed from progesterone, 17-OH-progesterone, and 11-deoxycortisol. To distinguish between effects of ACTH on the entry of precursors into cells and on enzyme activity within the cells, we examined the conversion of 11-deoxycortisol to cortisol in homogenized cell suspensions with and without pre-treatment with ACTH. Even in homogenized cells, prior treatment with ACTH enhanced the conversion of 11-deoxycortisol to cortisol. These findings clearly demonstrate that ACTH has a direct effect on the late phase of cortisol biosynthesis.
STUDIES ON CYCLIC NUCLEOTIDES IN THE ADRENAL GLAND
Authors: Shima Sumio , Kawashima Yoshiko , Hirai Masanao
Published: December 2008

Effects of ACTH and calcium on cyclic AMP and steroid production by the zona fasciculata-reticularis (the decapsulated fraction) from the rat adrenal cortex have been studied. Increasing concentrations of extracellular calcium enhanced the action of ACTH on cyclic AMP and steroid production. These effects of ACTH with calcium were prevented by lanthanum, but not by tetracaine or verapamil, suggesting that ACTH stimulation may be mediated by calcium through a process not involving the tetracaine- or verapamil-vulnerable step(s) of the calcium current.

High concentrations of external calcium itself increased cyclic AMP accumulation without any increase in steroidogenesis. A calcium ionophore, X537A was stimulatory for steroidogenesis but inhibitory with respect to cyclic AMP accumulation. Considered together with the findings of steroidogenic stimulation by low concentrations of ACTH without cyclic AMP increase, these results suggest that ACTH primarily increases intracellular calcium mobilization thus stimulating directly the steroidogenesis, which is independent of the cyclic AMP system. Relatively high concentrations of ACTH activate the adenylate cyclase, which depends on extracellular calcium to increase cyclic AMP levels and stimulation of steroidogenesis by the decapsulated fractions of the adrenal cortex.
PURIFICATION OF "INHIBIN" FROM HUMAN OVARIAN FOLLICULAR FLUID
Authors: Chari S. , Hopkinson C. R. N. , Daume E. , Sturm G.
Published: December 2008

Following the earlier demonstration of inhibin-like activity in human ovarian follicular fluid a method for its purification to apparent homogeneity is described. The fluid was converted to acetone powder and subjected sequentially to ammonium sulphate fractionation, gel chromatography on Sephadex G-200, continuous gradient ion-exchange chromatography on DEAE-cellulose, first with a pH gradient from 8.0 to 4.0 and then with a NaCl gradient to 1 m at pH 5.2. The active fraction from this step was subjected to gel filtration on Sephadex G-100 and finally passed through an Amicon Centriflo membrane CF-25 (cut off point: 25 000 m.w.). The ultrafiltrate was homogeneous by SDS-polyacrylamide gel electrophoresis, had a molecular weight of the order of 23 000 and was capable of suppressing serum gonadotrophin levels in the castrated male rats in as low a dose as 25 μg/rat.
INSULIN RECEPTORS, INSULIN SECRETION, AND GLUCOSE DISAPPEARANCE RATE IN PATIENTS WITH PERIODIC HYPOKALAEMIC PARALYSIS
Authors: Johnsen Torsten , Beck-Nielsen Henning
Published: December 2008

In a study of 6 male patients with periodic hypokalaemic paralysis (PHP), we found reduced insulin binding to monocytes as compared with a group of 25 normal subjects (P < 0.1). The decreased insulin binding was caused by the decreased binding affinity.

During induction of paralysis by a prolonged oral glucose load, one patient showed 24-h variations in the insulin binding to monocytes not differing from those observed in normals. After iv administration of glucose, these patients showed an elevated initial insulin response compared with the normals (P < 0.1). However, the iv glucose tolerance tests revealed normal glucose disappearance rates.

We conclude that changes in insulin receptor binding do not appear to be of pathophysiological significance for eliciting the parese attacks in PHP. However, the increased insulin response, following carbohydrate intake, might be of significance in the generation of paralytic attacks in patients with PHP.
OVARIAN BINDING AND INTRINSIC BIOLOGICAL ACTIVITY OF DESIALYLATED HUMAN CHORIONIC GONADOTROPHIN (ASIALO-hCG) IN IMMATURE SUPEROVULATED RATS
Authors: Odink J. , Brand E. C. , Van Hall E. V.
Published: December 2008

The present study was undertaken to investigate the effect of desialylation on the intrinsic in vivo biological activity of hCG. To block the hepatic uptake of asialo-hCG we investigated asialo-orosomucoid. The biological activity of hCG and asialo-hCG was estimated with the ovarian ascorbic acid depletion assay (OAAD). The uptake studies were performed with [125I]hCG and [125I]asialo-hCG.

Desialylation of hCG increased its hepatic uptake, almost completely abolished its ovarian uptake, and reduced its in vivo biological activity to less than 1 %. Administration of asialo-orosomucoid caused a reduction of the hepatic uptake of asialo-hCG to the level observed for hCG. The ovarian uptake increased, but was lower than observed for hCG, due to a considerably higher renal accumulation of asialo-hCG. The in vivo biological activity of asialo-hCG was approximately 1/5 of the activity of hCG when both were tested in the presence of asialo-orosomucoid.

To exclude the interference of renal accumulation, binding and biological activity were also investigated after bilateral nephrectomy. The uptake of radioactivity in the ovaries following injection of [512I]asialo-hCG and asialo-orosomucoid was then almost the same as observed after injection of [125I]hCG alone. When both preparations were now tested in the presence of asialo-orosomucoid, the in vivo biological activity of asialohCG appeared to be approximately 1/3 of the value obtained for hCG. It is concluded that the intrinsic in vivo biological activity of hCG is lowered by desialylation.
THE INFLUENCE OF AMINO ACIDS AND SOMATOSTATIN ON PROLACTIN AND GROWTH HORMONE RELEASE IN MAN
Authors: Bratusch-Marrain P. , Waldhäusl W.
Published: December 2008

The effect of an iv load of individual amino acids (alanine, arginine, histidine, leucine, phenylalanine, and valine) on serum prolactin (Prl) and growth hormone (GH) concentrations was studied in healthy adult males (n=5). A rise in both, Prl and GH with a maximal increment of 15.9±6.7 (se) ng/ml, and 12.4±4.9 ng/ml above basal levels, respectively, (P< 0.05) was observed after iv arginine. Following iv phenylalanine the mean peak level of Prl rose from 9.9 ± 3.5 to 29.9 ± 7.3 ng/ml (P <0.01), whereas GH concentration remained unchanged. Iv leucine however induced an immediate rise in GH, but not in serum Prl. Serum concentrations of both, Prl and GH, failed to increase upon the infusion of either alanine or histidine or valine. Additional somatostatin administration starting prior to amino acid infusion diminished the amino acid induced increase of both Prl and GH release.
THE EFFECT OF FOOD INTAKE ON INSULIN RECEPTOR IN MAN
Authors: De Pirro R. , Bertoli A. , Greco A. V. , Gelli A. S. , Lauro R.
Published: December 2008

Insulin binding to circulating monocytes was studied in 22 normal volunteers before and 1, 3 and 5 h after a 1400 Kcal meal.

Results indicate that 3 h after food intake there is an increase in the specific cell binding fraction (P < 0.001) with a change in receptor affinity. Data emerging from the present study demonstrate that there are rapid changes in insulin receptor properties during the day. These changes probably play a role in the regulation of the hormonal and metabolic pattern in normal subjects.
NSILA AND FOETAL GROWTH
Authors: Heinrich U. E. , Schalch D. S. , Jawadi M. H. , Johnson C. J.
Published: December 2008

Employing a sensitive competitive protein binding assay for NSILA (non-suppressible insulin-like activity), circulating levels of this somatomedin (SM) have been measured throughout pregnancy, at parturition, and in foetal and newborn sera. Acid-dissociable serum NSILA (mean ± sem) in 57 women was significantly higher during pregnancy (1106 ± 46 μU/ml), than in 11 adult non-pregnant control subjects (844 ± 22 μU/ml), but not correlated with week of gestation or with serum growth hormone (GH) or cortisol levels. At parturition, the NSILA concentration in 28 cord sera (598 ± 38 μU/ml) was significantly less than in the corresponding maternal sera (1039 ± 63 μU/ml). The NSILA levels in 23 premature newborns (370 ± 20 μU/ml) and 8 smallfor-gestational-age newborns (310 ± 46 μU/ml) were significantly less than in 33 term newborns (494 ± 18 μU/ml). Serum NSILA in 56 term and premature newborns exhibited a significant positive correlation both with gestational age and birth weight but not with serum GH or cortisol levels. These data suggest that the maternal-foetal growth-promoting system is a highly complex one in which NSILA levels both in maternal and foetal circulations appear to be under multifactorial control.
ENDOCRINE TESTICULAR FUNCTION IN VIVO AND IN VITRO IN INFERTILE MEN
Authors: Nieschlag E. , Wickings E. J. , Mauss J.
Published: December 2008

In order to detect any possible Leydig cell dysfunction associated with male infertility, the endocrine capacity of the testes was investigated in vivo and in vitro in 21 infertile men. Plasma testosterone was determined before and after 3 days of hCG stimulation. Testicular tissue obtained by bilateral biopsies was subjected to (1) histological examination, (2) determination of basal testosterone concentration and (3) incubation with hCG. Patients were grouped according to histology. In vitro basal and stimulated testicular testosterone was similar in patients with normal histology, Sertoli-cell-only syndrome and spermatogenic arrest. Tissue from patients with Leydig cell hyperplasia showed 3-fold higher basal testosterone levels and a greater response to hCG. All patients had plasma testosterone levels and responses to hCG in the normal range. There was no significant correlation between the data obtained in vivo and in vitro, indicating that testosterone determinations in peripheral blood do not necessarily reflect the intratesticular situation. There was no evidence for gross abnormality in Leydig cell function accompanying disturbed spermatogenesis.