bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of a correlation between thyrotrophin receptor binding inhibition and thyroid adenylate cyclase activation by immunoglobulins in Graves' disease before and during long-term antithyroid treatment
Authors: Bliddal Henning , Bech Karine , Petersen Per Hyltoft , Siersbæk-Nielsen Kaj , Friis Thorkild
Published: December 2008

In the present study we have measured in parallel thyrotrophin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating immunoglobulins (TACSI) in patients with Graves' disease (GD) both before and during long-term antithyroid treatment.

A statistical model based on the calculation of the differences (TACSI-TBII) is presented, comparing the changes in this parameter to the analytical variation. The correlation between TBII and TACSI in 52 patients with GD before treatment was: r = 0.58, P < 0.0001. During long-term antithyroid treatment of GD the 2 activities changed in parallel in 39 of 45 patients followed. In a few patients discrepancies were observed, and 1 patient, initially TACSI positive, developed adenylate cyclase inhibiting IgG during treatment but without detectable TBII.

In conclusion, 1) TBII and TACSI are significantly correlated in patients with GD both before and during long-term antithyroid treatment, 2) in some patients discrepancies between TBII and TACSI suggest, that these IgGs are heterogeneous with varying capacity for stimulation of the adenylate cyclase and receptor binding, and 3) adenylate cyclase inhibitory IgG without TBII activity was demonstrated in GD.
Pituitary and testicular functions in sexually mature rhesus monkeys under high-dose LRH-agonist treatment
Authors: Akhtar F. Bint , Wickings E. J. , Zaidi P. , Nieschlag E.
Published: December 2008

Treatment with high doses of LRH-agonists leads to a down-regulation of testicular LH/hCG receptors and is accompanied by a suppression of spermatogenesis in some laboratory animals. In order to test whether this may provide an approach to male fertility control, 4 adult rhesus monkeys were treated with very high doses of LRH-agonist, D-Ser(TBu)6-LRH-ethylamide (100 μg daily) for 10 weeks during the breeding season. There was a decrease in testicular volume after 3 weeks of treatment. Serum LH and testosterone levels were suppressed. Sperm counts were stimulated during the first 6 weeks of treatment. At the end of treatment sperm counts, although lower, were still in the normal range. The chronic treatment schedule resulted in a decrease in pituitary responsiveness to an acute challenge with 4 μg agonist iv, indicating a desensitization of the pituitary. However, the testosterone response remained unchanged. This study using extremely high doses of the agonist indicates that, compared to the rat, male primates are far more resistant to the suppressive effects of LRH-agonists.
Relationships between fat and plasma androstenone and plasma testosterone in fatty and lean young boars following castration
Authors: Bonneau M. , Meusy-Dessolle N. , Léglise P. C. , Claus R.
Published: December 2008

The effect of weight of fatty tissue on fat and plasma androstenone and on plasma testosterone relationships was studied in the young boar following castration. For this purpose, 9 boars were castrated at 175 days of age, plasma steroid levels were determined daily up to 10 days after orchidectomy and fat androstenone concentration was measured 1, 3, 6, 10 and 15 days after castration. The results show that the apparent half-life of stored androstenone is very variable between boars (range: 4 to 14 days) and do not depend on the weight of fatty tissue. The rate of elimination of plasma-androstenone is also very variable between boars. The rate of disappearance of fat androstenone following castration does not depend on the rate of androstenone release from fatty tissue to peripheral plasma but is more likely dependent on the intensity of plasma androstenone catabolism and elimination. Therefore, fat androstenone concentration in the intact boar is almost only depending on the equilibrium between the respective rates of testicular production and elimination.
Gonadectomy-induced reduction of blood pressure in adult spontaneously hypertensive rats
Authors: Masubuchi Yoshiko , Kumai Toshio , Uematsu Akiyo , Komoriyama Kenji , Hirai Masanao
Published: December 2008

Adult male and female spontaneously hypertensive rats (SHR-Okamoto, Kyoto) were gonadectomized when they were 17 weeks old. Intact SHR showed a progressive increase of their blood pressure with growth, attaining systolic pressure levels of 194–208 in males and 163–173 mmHg in females when they were 29–30 weeks old. During this same period, the gonadectomized animals showed a significant reduction in blood pressure ranging from 168–175 in males and from 158–163 mmHg in females. These studies indicate that male and female SHR gonadectomized at 17 weeks of age do not show the progressive blood pressure rise that occurs in intact SHR. There was no change in heart rate in either sex. Corticosterone (B) levels in plasma were increased in the orchidectomized males, and 18-OH-DOC levels in plasma were increased in the adrenal glands of ovariectomized females indicating that these hormonal changes probably do not play a role in SHR hypertension. It appears that gonadal and other hormones are involved in the pathogenesis of SHR hypertension.
Presence of melatonin in various cat brainstem nuclei determined by radioimmunoassay
Authors: Sallanon M. , Claustrat B. , Touret M.
Published: December 2008

Microdissected samples of juvenile cat brain tissue were assayed for melatonin content using a double antibody radioimmunoassay. Immunoreactive melatonin was consistently detected, albeit in variable amounts, in pineal, habenula, the region of the nucleus gracilis, gigantocellular reticular formation of the pons and medulla oblongata. Among the negative areas were raphe nuclei, substantia nigra and locus caeruleus. These findings suggest that melatonin may play a role in some structures of the central nervous system outside the pineal-hypothalamo-pituitary axis. This immunoreactive melatonin could reflect a local synthesis, or a tissular uptake of melatonin from blood or cerebrospinal fluid.
Effect of intravenous calcium on urinary cyclic adenosine-3',5'-monophosphate and hydroxyproline in children with hypoparathyroidism
Authors: Kruse Klaus , Kracht Ute
Published: December 2008

The effect of iv calcium on the urinary excretion of total adenosine-3',5',-monophosphate (cAMP) and total hydroxyproline (OH-P) was investigated in 5 children with parathyroid hormone (PTH)-deficient and PTH-resistant hypoparathyroidism, two of them being normocalcaemic during the study, in comparison to 4 healthy and 8 epileptic children and adolescents. Eighteen mg/kg body weight calcium, infused over 3 h, induced a decrease of cAMP to (mean ± sd) 82.1 ± 2.5% of the baseline value in controls and to 69.8 ± 9.7% in epileptic patients with an inverse correlation to the relative increase of serum calcium after the infusion in both groups (r = −0.75, P < 0.01). In contrast, the cAMP excretion increased after calcium load in the 5 hypoparathyroid children to 118.7 ± 14.9% of baseline despite a comparable serum calcium increase. OH-P decreased to (mean ± SD) 48.0 ± 6.8% of baseline in controls, 48.2 ± 12.7% in the epileptic patients and 39.4 ± 9.8% in the children with hypoparathyroidism, the differences between the three groups being statistically not significant.

It is concluded that the simple measurement of urinary cAMP before and after calcium infusion may provide a diagnostic tool to identify hypoparathyroid patients even in the normocalcaemic state. In contrast, the measurement of the calcium-induced suppressibility of OH-P does not discriminate these patients from subjects with normal parathyroid function.
Effects of starvation on oxidative metabolism and insulin release by isolated mouse pancreatic islets
Authors: Welsh Michael , Andersson Arne
Published: December 2008

Pancreatic islets were isolated from either 60-h-starved or fed mice and subsequently incubated in order to determine the insulin release in response to various secretagogues, rates of glucose, leucine or glutamine oxidation or the acetoacetate production from leucine. It was found that in contrast to findings with islets isolated from fed mice 16.7 mm glucose, 10 mM leucine and 10 mm α-ketoisocaproic acid did not stimulate the insulin release of islets isolated from starved mice. Moreover, the insulin release in response to leucine plus glutamine or glucose plus glutamine was decreased after starvation although these values were higher than those obtained for glutamine addition alone. Theophylline, however, restored partly the impaired insulin response to glucose and completely that to leucine or α-ketoisocaproic acid. Starvation was found to inhibit the islet glucose oxidation rate but the addition of theophylline was without effect irrespective of whether the islets were prepared from fed or starved mice. On the contrary, islet leucine oxidation was increased after starvation and again theophylline did not affect the islet leucine oxidation rate. Likewise, the islet acetoacetate production was increased after starvation. The glutamine oxidation rates were not affected by starvation, either when tested alone or together with glucose or leucine. It is concluded that although the starvation-induced impairment of glucose-stimulated insulin release may well be explained by an influence on the oxidative metabolism other factors are also involved as regards leucine-stimulated insulin release.
Monitoring ovarian function by a solid-phase chemiluminescence immunoassay
Authors: Weerasekera D. A. , Kim J. B. , Barnard G. J. , Collins W. P. , Kohen F. , Lindner H. R.
Published: December 2008

Ovarian function in women may be monitored by a simple, solid-phase, chemiluminescence immunoassay for the measurement of oestrone-3-glucuronide in diluted urine. An IgG fraction of antiserum to oestrone-3-glucuronyl-6-bovine serum albumin is passively adsorbed to the walls of polystyrene tubes. Oestrone-3-glucuronyl-6-aminoethyl-ethyl-isoluminol is the labelled antigen. Daily samples of early morning urine are diluted in buffer (1:100; v/v), and 100 μl removed, in duplicate, for assay. After the binding reaction (1 h at 4°C), the solution is removed by aspiration. The antibody-bound fraction is washed once with buffer (400 μl). Sodium hydroxide (2n, 200 μl) is added and the mixture incubated for 60 min at 22°C. Luminescence is initiated by oxidation of the label with microperoxidase/hydrogen peroxide and the signal integrated for 10s.

An evaluation of the method gave the following values: sensitivity of calibration curve 3.12 ± 0.75 pg/tube (mean ± sd). The intra-assay precision (CV%) was 9.52 (20 replicates; 38.4 ± 3.66 nmol/l) and 8.61 (15 replicates; 102.4 ± 8.82 nmol/l). The inter-assay precision (CV%) was 11.9 (mean of 4 pools−7.03, 23.16, 52.11 and 117.53 nmol/l over 2 months). The mean bias was −0.78% over the range 28 to 448 nmol/l and different aliquots (equivalent to 0.25 to 4 μl) of daily early morning urine gave results that were in good agreement. The concentration (nmol/l; mean ± sd) of oestrone-3-glucuronide in samples of early morning urine collected from healthy women during the early follicular, periovulatory and luteal phases of the menstrual cycle were 40.2 ± 9.9, 102.3 ± 39.4 and 84.3 ± 13.3 nmol/l, respectively. In addition, the results obtained from the analysis of EMU throughout 6 complete menstrual cycles were in good agreement with the values derived by radioimmunoassay (r = 0.94).
The renin-aldosterone system in pre-eclampsia, essential and transient hypertension during pregnancy, and normotensive pregnant and non-pregnant control subjects
Authors: Pedersen E. B. , Rasmussen A. B. , Johannesen P. , Kornerup H. J. , Kristensen S. , Lauritsen J. G. , Wohlert M.
Published: December 2008

Plasma renin concentration (PRC), plasma aldosterone concentration (PAC), and blood pressure were determined in the third trimester in pregnancy, 5 days and 6 months after delivery in pre-eclampsia, essential and transient hypertension in pregnancy and in normotensive pregnant and non-pregnant control subjects. PRC and PAC were elevated several fold above non-pregnant level in all groups during pregnancy. In pre-eclampsia PRC and PAC were 220 and 160%, respectively, above the levels 6 months after delivery, and thus lower than the corresponding values, 360 and 402%, in normotensive pregnancy. In essential and transient hypertension PRC and PAC increased to the same degree as during normotensive pregnancy. Urinary sodium excretion, serum sodium and creatinine clearance were reduced in pre-eclampsia, but not in essential and transient hypertension when compared to normotensive pregnant controls. All the parameters determined were the same as in non-pregnant controls 6 months after delivery in all groups. There were no correlations between blood pressure and PRC or PAC in any of the groups neither in pregnancy nor after delivery. It is concluded that the renin-aldosterone system is stimulated in lesser degree in pre-eclampsia than in both essential hypertension, transient hypertension and normotensive pregnancy, and there was no evidence for a causal relationship between the renin-aldosterone system and blood pressure neither in normotensive nor hypertensive pregnancy.
Specific binding sites for epidermal growth factor and its effect on human chorionic gonadotrophin secretion by cultured tumour cell lines: comparison between trophoblastic and non-trophoblastic cells
Authors: Hirata Yukio , Sueoka Satoru , Uchihashi Masahito , Yoshimoto Yoshio , Fujita Takuo , Matsukura Shigeru , Motoyama Teiichi
Published: December 2008

Using human trophoblastic (SCH) and non-trophoblastic (HeLa S3) tumour cell lines, specific binding sites for epidermal growth factor (EGF), a potent stimulator of growth in many tissues, and its effect on secretion of human chorionic gonadotrophin (hCG) and/ or its subunits were compared between these two tumour cells.

Both SCH and HeLa S3 cells possessed two populations of specific binding sites for 125I-labelled EGF: the high affinity (Kd ∼10−10m) and the low affinity (Kd ∼ 7 × 10−10 m) system. Tetradecanoyl phorbol acetate (TPA), a tumour promotor, showed a potent competitor of labelled tracer binding to its receptor sites in both cell lines. EGF stimulated both hCG-α and hCG and/or hCG-β secretion in a dose-responsive manner from SCH cells, whereas it had no effect on hCG-α secretion from HeLa S3 cells. In contrast, dibutyryl cyclic AMP plus theophylline, a phosphodiesterase inhibitor, enhanced hCG-α secretion from both cells, while TPA had no effect in either cells.

These data suggest that EGF may play a physiological role in hCG secretion from trophoblastic tissues and that the mechanism by which hCG and/or its subunits are secreted may differ between trophoblastic and non-trophoblastic tumour cells.
Potentiation by prolactin of the luteotrophic effect of oestradiol in the pregnant rat
Authors: Rodway Richard G. , Garris David R.
Published: December 2008

The luteotrophic effects of elevated prolactin levels with or without concomitant oestradiol treatment were investigated in the pregnant rat after hysterectomy or hysterectomy plus hypophysectomy. On day 2 of pregnancy, rats were given a single pituitary transplant beneath the renal capsule and were subsequently hysterectomised on day 12. This treatment delayed the next ovulation (as judged by vaginal di-oestrus length) compared to sham-transplanted controls, but did not prevent the fall in serum progesterone concentrations (i.e. luteolysis) resulting from hysterectomy. The administration of 1 or 2 pituitary homo-transplants on day 12 at the time of hysterectomy again prolonged the di-oestrus length but did not prevent subsequent luteolysis. However, daily treatment with 100 μg of oestradiol given to rats which received 2 pituitary transplants on day 2 and which were then hysterectomised on day 12, did result in a maintenance of serum progesterone levels compared to those of oil-treated controls.

In a separate study, pregnant rats were hysterectomised and hypophysectomised on day 12. Administration of either 1 or 2 pituitary transplants failed to maintain luteal function. However, concomitant daily treatment with 100 μg of oestradiol from day 12 onward prevented luteolysis and re-instated the day 12–16 rise in serum progesterone common to the intact pregnant rat. Progesterone levels then declined slowly until the end of the sampling period (day 23). Serum prolactin concentrations rose steadily for the first 10 days after insertion of pituitary transplants on day 12 of pregnancy. These data indicate that prolactin and oestradiol can act synergistically to stimulate progesterone secretion from the rat corpus luteum but only in the absence of the in situ pituitary; the effect is not seen unless hypophysectomy has been performed.
Plasma progesterone levels during long-term treatment with levonorgestrel silastic implants
Authors: Croxatto Horacio B. , Diaz Soledad , Pavez Margarita , Miranda Patricia , Brandeis Astrid
Published: December 2008

Plasma progesterone levels were measured in 113 women using a subdermal implant containing 200 mg levonorgestrel (NORPLANT™*) in an attempt to assess the roles of anovulation and inadequate luteal function in the contraceptive action of this method. Twenty-two women using an IUD (Copper T 200) served as a control group.

Blood samples were taken twice a week for 6 consecutive weeks. This was done one to four times in each subject during the first 7 years after insertion of NORPLANT. Plasma progesterone was measured by a specific RIA and criteria based upon normal values in this laboratory were used to define each set of samples as ovulatory, uncertain or anovulatory. The rate of anovulation varied between 25 and 80% throughout the 7 years. The highest rate was observed during the first year of treatment. The rate of anovulation was significantly correlated with the plasma levels of levonorgestrel. Varying degrees of inadequate corpus luteum function were detected among NORPLANT users. All sets of samples in the control group were ovulatory and compatible with normal luteal function.

These results clearly show that continuous administration of levonorgestrel by means of NORPLANT interferes with ovulation and/or luteal function in a significant proportion of cycles throughout the first 7 years of use.
Changes in mechanical properties, thermal stability, reducible cross-links and glycosyl-lysines in rat skin induced by corticosteroid treatment
Authors: Oxlund Hans , Sims Trevor , Light Nicholas D.
Published: December 2008

The effects of systemic cortisol treatment on the biophysical and biochemical properties of skin were investigated. Rats were injected sc with cortisol for 14, 60 and 120 days and samples of lumbar skin were studied.

Corticosteroids exert a biphasic effect on the strength of skin: 1) a relatively fast increase in the strength and stability, caused by an increased collagen cross-linking and 2) an inhibited collagen synthesis which ultimately results in a thinning of the skin and a decrease of collagen content consistent with clinical observations. The thermal stability is increased indicating an increased proportion of thermostable cross-links in skin collagen. No changes are observed in the percentage type III collagen with respect to type I collagen. Increased amounts of glucose attached to the ε-amino group of lysine residues in the collagen are found after long-term treatments, an alteration which may play a role in hampering the tissue functions.
Effects of starvation on circadian variations of plasma TSH in rats
Authors: Hugues J. N. , Reinberg A. , Jordan D. , Sebaoun J. , Modigliani E. , Burger A. G.
Published: December 2008

Diurnal fluctuations of plasma TSH were investigated in ad libitum fed rats as well as after a 3 day starvation period in order to study the relationship between the circadian pattern of TSH secretion and nutritional status. Our study showed the persistence of a circadian TSH rhythm after a 3 day starvation without any change in the amplitude of plasma TSH variations. However, the 24 h average plasma TSH levels were significantly lower. A suggestive acrophase occurred at the same period of the day in starved and fed rats. Our results suggest that the control of plasma TSH concentrations and nycthemeral rhythm are not closely related and may even possibly be independent of one another.
Somatostatin-28 like immunoreactivity in normal and tumour tissue from duodenum and pancreas
Authors: Ito Seiki , Yamada Yukio , Iwanaga Toshihiko , Kaneko Hiroshi , Shibata Akira
Published: December 2008

Radioimmunoassay using labelled somatostatin-14 revealed that components of somatostatin-28 antisera cross-reactive to somatostatin-14 were removed by absorption of somatostatin-28 antisera with sepharose 4B-somatostatin-14. Indirect immunofluorescence techniques using specific antisera against somatostatin-28 were carried out in normal pancreas, duodenum, a somatostatinoma in the duodenum, and pancreatic tumour cells containing somatostatin-14 positive cells, in order to establish if somatostatin-28 is present in normal and pathological tissues. Somatostatin-28 like immunoreactivity was present in pancreatic islets cells and in the epithelial cells of the duodenum as well as in the duodenal somatostatinoma and in pancreatic tumour cells. Furthermore, cells reacting with specific antisera against somatostatin-28 were identical to those with somatostatin-14 antisera in normal and pathological tissues. The findings suggested that somatostatin-28 like immunoreactivity may be constantly present in the tissues where somatostatin like immunoreactivity was detected using somatostatin-14 antisera. However, further studies are necessary to clarify whether somatostatin-28 and somatostatin-14 were independently present in these tissues, in other words, whether somatostatin-14 may be produced from somatostatin-28 or not, since somatostatin-14 antisera had cross-reactivities to somatostatin-28.
In vitro conversion of cholesterol into aldosterone and cortisol in different zones of the bovine adrenal cortex
Authors: Karlmar Karl-Eric
Published: December 2008

The individual steps in the formation of aldosterone and cortisol from cholesterol were assayed in different subcellular preparations from the inner and outer zones of bovine adrenal cortex. In zona glomerulosa the 11β-, 18- and 21-hydroxylase activities were relatively high, whereas the 17α-hydroxylase activity was relatively low. Cholesterol side-chain cleavage and 3β-hydroxysteroid-Δ5-oxidoreductase activity were similar in zona glomerulosa and zona fasciculata-reticularis. The differences were however only quantitative. In no case one specific fraction was totally devoid of enzyme activity. The total content of mitochondrial cytochrome P-450 was relatively high in zona fasciculata-reticularis whereas the content of microsomal cytochrome P-450 was similar in the two fractions. In view of the relatively small differences observed, it seems likely that other factors than distribution of the above enzymes are of major importance for the specific production of gluco- and mineralocorticoids in the two layers.
The preovulatory decline in follicular oestradiol is not required for ovulation in the rabbit
Authors: LeMaire William J. , Janson Per O. , Källfelt Björn J. , Holmes Paul V. , Cajander Stefan , Bjersing Lars , Ahrén Kurt E. B.
Published: December 2008

Using a method of in vitro perfusion of the rabbit ovary with a chemically defined medium in a recirculation system, normal appearing follicular ruptures occurred following exposure of the ovaries to hCG in vivo (100 IU) or following addition of LH (0.25 μg/ml of NIH B9) to the perfusate. The addition of oestradiol17β (10 μg/ml) to the perfusate did not inhibit these follicular ruptures, although the follicular fluid oestradiol contents were increased more than 100-fold as compared to the control side not receiving the addition of oestradiol. These data suggest that the physiological decline of follicular oestrogen, normally observed in vivo prior to ovulation in the rabbit, is not required as part of the mechanism of ovulation and that normal appearing ovulations can occur even though follicular oestrogen levels are kept artificially elevated.
Synthesis and storage of hormonal granules in cultured cells of the rat pituitary pars intermedia
Authors: Bäck Nils , Hervonen Heikki , Rechardt Leena
Published: December 2008

Tissue from the pars intermedia of the pituitary from new-born and adult rats was maintained in tissue culture for periods up to 14 days. Both new-born and adult rat pars intermedia cells showed active production of secretory granules during tissue culture, and also showed formaldehyde-chloral induced fluorescence. Immunohistochemically, β-endorphin could be demonstrated in cultured pars intermedia cells.

In contrast to the appearance of the pars intermedia cells in vivo, the granules in the cultured cells were most often seen along the cell membrane, and the cytoplasm was often dominated by clear vacuoles slightly larger than the granules. No exocytotic figures were observed in the cultured cells. The mechanism of hormonal release from the organ, if release does occur, thus remains obscure.

In conclusion, cultured cells from the rat pituitary pars intermedia continue their production of hormonal granules in tissue culture, and thus form a valuable tool for further investigations on the complex regulation of hormonal secretion form the organ.
Role of thyrotrophin-releasing hormone in the development of pituitary-thyroid axis in four anencephalic infants
Authors: Pezzino Vincenzo , Distefano Giuseppe , Belfiore Antonio , Filetti Sebastiano , Mazzone Domenico , Grasso Sebastiano
Published: December 2008

Anencephaly provides a unique model for studying endocrine functions in absence of hypothalamic influence. We previously reported that in anencephalic newborns both pituitary TSH-secreting cells and the thyroid were normal and were able to function if adequately stimulated. In order to verify if the normal development of the pituitary-thyroid axis in these infants depends on TRH of extrahypothalamic origin, we measured endogenous TRH levels in the clear fluid of a cyst of the cerebro-vasculosa in 4 anencephalic newborns. In these cysts we also injected 200 μg of synthetic TRH and evaluated TSH response in peripheral blood samples.

Endogenous TRH was detectable in the cysts of the cerebro-vasculosa in 3 of the 4 infants. In all 4 cases serum TSH sharply increased after TRH administration. Our data suggest that the normal development of the pituitary-thyroid axis in anencephalic infants either requires no TRH or depends on extrahypothalamic TRH. In this latter case TRH produced by other areas of the central nervous system might be secreted into the cysts of the cerebro-vasculosa, actively transported to the hypophyseal vessels, and might thus reach the pituitary to stimulate TSH-cells growth and function.
Gonadotrophin-secretion in adrenocortical insufficiency: impact of glucocorticoid substitution
Authors: Vierhapper H. , Waldhäusl W. , Nowotny P.
Published: December 2008

In patients with deficient endogenous glucocorticoid production due to primary adrenal insufficiency (n = 4) or bilateral adrenalectomy (n = 2) a rise in LRH-stimulated concentrations of LH was seen following withdrawal of substitution therapy for 84 h. Consecutive re-administration of glucocorticoids (dexamethasone 2.0 mg/day for 3 days) resulted in increased basal concentrations of LH and FSH and a diminished secretory response of LH upon iv LRH (100 μg). Five patients substituted with glucocorticoids because of adrenocortical insufficiency presented upon the administration of exogenous ACTH1-24 with unchanged basal and LRH-stimulated concentrations of LH and FSH as compared to a placebo experiment. These data suggest that the withdrawal and subsequent re-administration of glucocorticoid substitution alters basal and stimulated concentrations of gonadotrophins in patients with adrenocortical insufficiency, thus providing evidence for the importance of adequate glucocorticoid supply in the regulation of gonadotrophin secretion.
Effect of gonadotrophin-releasing hormone (GnRH) and GnRH agonists upon accumulation of progesterone, cAMP and prostaglandin in isolated preovulatory rat follicles
Authors: Hillensjö Torbjörn , LeMaire William J. , Clark Martin R. , Ahrén Kurt
Published: December 2008

To study the acute and direct effects of GnRH agonists preovulatory follicles were isolated from PMSG-treated immature rats and incubated for 15–360 min in modified Kreb's bicarbonate buffer. The levels of cAMP, prostaglandin E, and progesterone were analysed in the tissue and/or incubation media. GnRH and two GnRH agonists produced a dose-dependent stimulation of progesterone production with maximal levels 5–6-fold higher than the control group. As compared to LH the magnitude of this effect was small and was detected only after 240–360 min of incubation. GnRH also stimulated prostaglandin E accumulation and this effect was as pronounced as for LH. There were no detectable changes in cAMP levels for any concentration of GnRH when the incubation time varied between 15 and 120 min whether or not a phosphodiesterase inhibitor was present, but after 240 min of incubation a 2-fold incease in cAMP was found. Consistent with previous results, LH caused a pronouced (40–50-fold) increase in follicular cAMP which was already detectable after 15 min of incubation. Indomethacin abolished the rise in prostaglandin E induced either by GnRH or LH but did not affect the response in terms of cAMP or progesterone, and did not affect the stimulation of meiotic maturation of the follicle-enclosed oocytes caused by the hormones. It is concluded that GnRH can exert acute and LH-like stimulatory effects on the preovulatory rat follicle but that the mechanism of GnRH action is different from that of LH.
The effect of prostaglandins in the rat ovary: specific or unspecific stimulation of cAMP, cGMP and progesterone?
Authors: Schindler Hubert , Müller Ulrich , Siebers Jan Willem
Published: December 2008

Ovarian membranes of the rat do not specifically bind prostaglandin E2 at any stage of development. Attachment of [3H]prostaglandin E2 in the presence of an excess of unlabelled prostaglandin E2 increased in a linear fashion and was not saturable. Prostaglandin E2 stimulated cAMP accumulation by ovarian cells of all developmental stages. This effect was not saturable. An effect of prostaglandin E2 on cGMP levels was not observed. At high concentrations of prostaglandin E2 an increase of ovarian progesterone synthesis was detected. In comparison hCG stimulated progesterone synthesis at much lower concentrations. PGF2α increased cellular and extracellular cAMP at 1000-fold higher concentrations than PGE2 and did not affect cGMP levels.
Imitation of normal plasma growth hormone profile by subcutaneous administration of human growth hormone to growth hormone deficient children
Authors: Christiansen J. Sandahl , Ørskov H. , Binder C. , Kastrup K. W.
Published: December 2008

The time course of plasma growth hormone (hGH) levels following sc and im injection of hGH was studied in 12 children with growth hormone deficiency who had received long-term treatment with im injections of highly purified hGH. Also the spontaneous diurnal GH levels in 8 normal children of comparable age were recorded.

Blood samples were obtained during 24 h after im and sc injections of 4 IU/m2 hGH and analysed for immunoreactive hGH. While a median peak value of 160 ng/ml (range 135 to 475 ng/ml) was obtained 2 h after im injection, sc injection resulted in a more sustained elevation reaching 41 ng/ml (range 32 to 51 ng/ml) at 6 h subsiding slowly with a median concentration of 15 ng/ml (range 5–24 ng/ml) persisting after 14 h.

Gel chromatography demonstrated that the hGH immunoreactivity of blood samples obtained as late as 14 h after sc injection had unaltered molecular size.

Seven of the patients were further studied after sc injection of 2 IU/m2 at 20.00 h instead of in the morning. A plasma profile was attained during the night which roughly approximated the average nocturnal plasma pattern of the normal children.
Effect of purified somatomedins on thymidine incorporation into lectin-activated human lymphocytes
Authors: Schimpff Rose-Marie , Repellin Anne-Marie , Salvatoni Alessandro , Thieriot-Prevost Geneviève , Chatelain Pierre
Published: December 2008

These data describe the effects of purified preparations of several growth factors on thymidine incorporation into phyto-haemagglutinin-activated (PHA) human lymphocytes. The somatomedins selected for this study included human somatomedins A and C, insulin-like growth factors (IFG1) and IGF2) and multiplication stimulating activity (MSA). Assays were carried out with and without serum. Complementary assays were performed with a low-molecular serum ultrafiltrate added to somatomedin C and to MSA. We found that all the peptides tested, except MSA, stimulated thymidine incorporation into PHA-activated lymphocytes in a dosedependent manner, even though different doses were required to obtain a response. The data reported point out the multiplicity and the interrelationships of the serum factors involved in the stimulation of human cells growth.
Organ culture of the anterior pituitary in a synthetic medium. An immunocytochemical study
Authors: Bégeot M. , Li J. Y. , Dubois M. P. , Dubois P. M.
Published: December 2008

Anterior pituitaries removed from human foetuses and rat neonates were maintained in organ culture after using three different media. A comparative immunocytological study of the different cell-types was made in the three media used. In the first medium containing foetal calf serum the different cell-types were present but their frequency in the cultured explants depended upon their representation in the tissue at the beginning of the culture. In the medium without any adjunction, the most characteristic feature was the shrinkage of the cultured tissue. In the third medium in which foetal calf serum was replaced by insulin the evolution of the explants was the same as in the first medium. All the cell-types were represented with a particular development of gonadotrophic cells. In conclusion it seemed that the third synthetic medium can be used in order to study anterior pituitary cells in vitro.
Radioimmunological measurements of total LH in sheep pituitary cells
Authors: McIntosh R. P. , McIntosh J. E. A.
Published: December 2008

Procedures commonly used to extract LH from pituitary cells in order to measure total cell content were compared in four cell preparations. It was shown in 81 samples of cells suspended in 1 mm EDTA or 50 mm NaHCO3 that after freezing and thawing followed by any of a variety of treatments, there were no significant differences in the amounts of LH measured by RIA relative to the arbitrarily chosen reference treatment of vigorous pipetting. The additional treatments were multiple freezing and thawing, homogenisation, sonication, homogenisation in 25–100 mm Na2CO3 followed by rapid neutralisation, or none. The consistency of the results suggested that the same cellular pools of LH were being made accessible for measurement with all treatments. However, use of the more vigorous conditions of 1–2.5 m urea, 1% Triton X-100, or sonication on ice in 100 mm Na2CO3 decreased the amount of measurable hormone presumably due to its modification. In two cell preparations, homogenisation of cells in 100 mm Na2CO3 produced an additional 45% of measurable LH not accessible using other treatments nor from the source material in two other preparations.
Thyroid function in Gunn rats with genetically altered thyroid hormone catabolism
Authors: Benathan M. , Lemarchand-Béraud Th. , Berthier C. , Gautier A. , Gardiol D.
Published: December 2008

Due to a congenital deficiency in uridine diphosphate glucuronosyl transferase (UDP-GTase), Gunn rats display an impaired biliary elimination of both bilirubin and thyroid hormones, resulting in hyperbilirubinaemia and hyperthyroxinaemia. They also present a pigmented thyroid gland. In order to assess the effect of the hyperthyroxinaemia on the regulation of the thyroid function, the [125I]thyroid uptake and distribution into soluble proteins, the [127I]thyroid soluble content, the levels of circulating T4, total and free, T3, reverse T3 (rT3) and TSH as well as the TSH response to TRH have been determined in Gunn (G) and Wistar (W) rats aged 3 to 56 weeks.

Gunn rats possess a goitre with increased soluble [127I]-iodine content. The [125I]thyroid uptake and incorporation into soluble proteins were similar in both strains, but the DIT fraction was higher, whereas the MIT, T4 and T3 fractions were lower compared to control rats. Total thyroxinaemia was greatly increased in Gunn rats as expected (G:5.1–9.1 vs W:3.1–4.6 μg/dl) whereasfree thyroxinaemia was increased only by 25–50%. The differences in total-T4 and bilirubin serum levels between Gunn and Wistar rats 6 to 56 weeks old were found to be in direct correlation. In addition, Gunn rats presented normal serum T3 levels, but increased rT3 (G: 0.10–0.45 vs W:<0.03–0.27 ng/ml) and TSH (G:0.33–0.75 vs W:0.11–0.43 ng/ml) serum levels. The TSH response to TRH was however normal, but the return to basal values was delayed in comparison to Wistar rats. Evolution of thyroid parameters with age was similar in both strains, i.e. opposite variations in T3 and rT3 serum values during the post-natal period and decreasing serum T4 concentrations, pituitary TSH content and TSH response to TRH during the adult life.

In conclusion, the association of hyperthyroxinaemia with decreased T3/rT3 serum ratio suggests that Gunn rats may have, in addition to the impaired biliary excretion of iodothyronines, a modified T4 deiodination pattern with probably increased rT3 formation. A diminished T4 availability and/or a decreased T4 to T3 conversion in the thyrotrophe cell might explain the normal TSH response to TRH. These data reflect a partial peripheral resistance to the hyperthyroxinaemia, which may represent an adaptation mechanism.
Prospective and retrospective studies of zinc concentrations in serum, blood clots, hair and urine in young patients with insulin-dependent diabetes mellitus
Authors: Hägglöf Bruno , Hallmans Göran , Holmgren Gösta , Ludvigsson Johnny , Falkmer Sture
Published: December 2008

Two main diabetic groups were investigated, viz. one consisting of 19 diabetic children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) (median age 10 years) where a prospective study was made, and one where a retrospective examination was performed of 73 patients (median age 14 years) with a mean duration of IDDM of 7 years; 83 healthy school children (median age 13 years) served as controls. In both groups of diabetic children more zinc was excreted in the urine than in the controls. At onset of IDDM, serum and blood clot zinc concentrations were reduced with a gradual increase towards normal within 1 month of insulin therapy. The zinc concentrations in hair did not differ from those of the controls. No correlation were found between zinc levels in serum, blood clots, urine and hair on one hand and the concentrations of albumin and glucose in serum and urine on the other.
Trilostane in the management of Cushing's syndrome
Authors: Semple C. G. , Beastall G. H. , Gray C. E. , Thomson J. A.
Published: December 2008

Trilostane has been used to treat 6 patients with Cushing's syndrome, 4 with an adrenal adenoma and 2 with pituitary driven disease. Three patients responded clinically and biochemically to trilostane. Although effective in some cases of Cushing's syndrome, the variability of the effect of trilostane may limit its usefulness as a therapeutic agent.
Effects of angiotensin II on the zona glomerulosa of sodium-loaded dexamethasone treated rats administered or not with maintenance doses of ACTH: stereology and plasma hormone concentrations
Authors: Mazzocchi Giuseppina , Meneghelli Virgilio , Nussdorfer Gastone G.
Published: December 2008

The trophic effects of angiotensin II on the rat zona glomerulosa were investigated by stereological and radioimmunological methods. Angiotensin II was not able to reverse the sodium-loading and dexamethasone-induced inhibition of the growth and steroidogenic capacity of the zona glomerulosa. However, if the sodium-loaded dexamethasone-treated rats were given maintenance doses of ACTH, angiotensin II exerted a strong adrenoglomerulotrophic effect. The hypothesis is advanced that the co-operation of ACTH and angiotensin II is required in the maintenance of the morphologic and enzymatic integrity of the rat zona glomerulosa.
Prolactin binding by testes of unilaterally cryptorchid rats: the effect of hCG, testosterone, prolactin and orchiopexy
Authors: Hochberg Zeev , Amit Tamar , Youdim Moussa B. H. , Bar-Maor Jehuda A
Published: December 2008

The effect of unilateral cryptorchidism on prolactin binding to the testes was studied in the rat. Cryptorchidism was rendered surgically for 3 weeks and 3, 6 and 9 weeks later prolactin binding was measured in testicular homogenates. Prolactin binding to the cryptorchid testes decreased significantly at 3 weeks with a further decrease at 6 and 9 weeks. Binding by the contralateral testes decreased at 3 weeks and increased at 6 and 9 weeks. To examine the possible mechanism of these changes one group of rats was treated for 5 weeks with testosterone and another with hCG. Testosterone treatment resulted in a significant fall in prolactin binding to normal, cryptorchid and contralateral testes. hCG also produced a slight but significant reduction in prolactin binding. To study the effect of surgical relocation of the testes into the scrotum, orchiopexy was performed in another group of rats. Orchiopexy increased prolactin binding only if performed 3 weeks after cryptorchidism. At 6 and 9 weeks after cryptorchidism orchiopexy did not increase prolactin binding. Treatment of cryptorchid rats with prolactin for 5 weeks induced an increase in prolactin binding to control, cryptorchid and contralateral testes. It is concluded that testicular atrophy follows upon placement of a testis within the peritoneal cavity. This atrophy lowers the total amount of prolactin binding and increases binding to the contralateral testes. Intratesticular concentration of testosterone may play a major role in the decrease of prolactin binding. Orchiopexy improves prolactin binding only if performed before 6 weeks of age. Administration of prolactin augments prolactin binding to the testes, irrespective of their location.
Effects of desglycinamide-arginine-vasopressin (DG-AVP) on memory processes in diabetes insipidus patients and non-diabetic subjects
Authors: Laczi F. , van Ree J. M. , Wagner A. , Valkusz Zs. , Járdánházy T. , Kovács G. L. , Telegdy G. , Szilárd J. , László F. A. , de Wied D.
Published: December 2008

The effects of desglycinamide9-arginine8-vasopressin (DG-AVP) on memory processes have been studied in patients with central diabetes insipidus (DI) and in non-diabetic control patients. Acute im injection of DG-AVP improved some aspects of short-term memory. Subchronic intranasal administration of DG-AVP facilitated short-term memory more consistently and in addition improved long-term memory. DG-AVP increased the attention, but only in the non-diabetic subjects. The effects of DG-AVP on memory processes persisted after discontinuation of treatment. DG-AVP did not affect the parameters for water and electrolyte metabolism, blood pressure and pulse rate neither in DI nor in the control patients. Thus, the memory effects of DG-AVP are probably mediated by a direct action on the central nervous system.
T lymphocyte subpopulations in Graves' disease: relationship with clinical conditions
Authors: Bagnasco M. , Canonica G. W. , Ferrini S. , Biassoni P. , Melioli G. , Ferrini O. , Giordano G.
Published: December 2008

T lymphocytes were franctionated according to their receptors for IgG (TG) or IgM (TM) and scored in 37 patients with Graves' disease (17 hyperthyroid and untreated, 10 euthyroid on antithyroid drugs, 10 in long-term remission after radioiodine therapy). TG percentages were very low both in untreated and in drugtreated patients. By contrast, normal TG levels were observed in patients in long-term remission. These data are consistent with the hypothesis of a defective suppressor cell activity in Graves' disease.
Erythrocyte insulin receptors and insulin sensitivity in adrenocortical insufficiency. Report of a case of diabetes mellitus type I with superimposed Addison's disease
Authors: Ivarsson S. A. , Nilsson K. O. , Thorell J. I.
Published: December 2008

Studies on erythrocyte insulin receptors were performed in a boy with type I diabetes mellitus and superimposed adrenocortical insufficiency before and during treatment with hydrocortisone and 9-α-fluoro-hydrocortisone. The development of the adrenal insufficiency was associated with a progressively increased sensitivity to insulin which reverted after therapy. The maximum specific insulin binding of the erythrocytes was low during threatening addisonian crisis (6.9%) but normalized during hydrocortisone treatment (12.0%). These findings suggest that the increased insulin sensitivity characteristic for adrenocortical insufficiency is not an effect of an increased insulin receptor concentration and that hypocortisolaemia is associated with a down-regulation of the insulin receptors.
Comparison of circadian rhythms of the renin-angiotensin-aldosterone system and electrolytes in clinically healthy young women in Fukuoka (Japan) and Minnesota (USA)
Authors: Kawasaki Terukazu , Uezono Keiko , Ueno Michio , Omae Teruo , Matsuoka Midori , Haus Erhard , Halberg Franz
Published: December 2008

Circadian rhythms of the renin-angiotensin-aldosterone (R-A-A) system and electrolytes were evaluated in young healthy Fukuokan (Japan) and Minnesotan (USA) women. A similar protocol was used and each group remained on its usual diet. Blood was taken for 24 h at 4 h intervals from 8 a.m. during which time urine samples were also collected. The determinations in both groups were made in a laboratory in Japan. Plasma renin activity, plasma aldosterone concentration and aldosterone excretion rate showed similar circadian rhythms in both groups. However, those values at each sampling time and each span were always significantly higher in the Americans while the urinary Na and Cl excretions and blood pressure were higher in Japanese. The significant differences in the R-A-A system and blood pressure levels between these two groups may be due to the large amount of salt consumed by the Japanese.