bluuebunny/crossref_metadata_2025 huggingface dataset:
The vasopressin response to microinjections of norepinephrine into the brain of the conscious pig
Authors: Forsling Mary L. , Parvizi Nahid
Published: December 2008

Abstract. The possibility that the amygdala influences the release of vasopressin has been raised by the observation that electrical stimulation of this area results in vasopressin release in the conscious animal. Therefore the effect on vassopressin concentrations has been studied by microinjections of norepinephrine into the amygdala of the conscious miniature pig. The studies were performed on castrated male and female pigs with chronically implanted cannulae in the brain and in the external jugular vein. Lysine vasopressin concentrations were determined using a specific sensitive radioimmunoassay. Microinjections of 1 μl 0.12 m sodium chloride were without effect. Injections of norepinephrine in the dose range 10−4–10−10m had no effect in the male animal but a significant vasopressin response could be obtained in the females.
Proteinuria in autoimmune thyroid disease
Authors: Weetman A. P. , Tomlinson K. , Amos N. , Lazarus J. H. , Hall R. , McGregor A, M.
Published: December 2008

Abstract. We have investigated the prevalence of proteinuria in patients with Graves' disease and chronic autoimmune thyroiditis attending a routine thyroid clinic. Using the urine protein creatinine index, proteinuria was found in 29.8% of patients with autoimmune thyroid disease and in 9.5% of patients attending the same clinic but without these conditions. When patients with Graves' disease were treated with 131I, proteinuria measured by 24 h collections developed in 9 of 14 patients without pre-existing proteinuria and appeared to diminish in 4 patients in whom proteinuria had been present before treatment. The prevalence and fluctuation of proteinuria was independent of thyroglobulin and microsomal antibody levels. We were unable to confirm previous reports of a high prevalence of circulating immune complexes in autoimmune thyroid disease; complexes were detected in only 7.9% of patients and did not correlate with proteinuria. The causes of mild proteinuria in autoimmune thyroid disease are not apparent, but previous case reports suggesting that membranous glomerulonephritis is associated with Graves' disease, albeit rarely, indicate that immunological mechanisms may be implicated.
Quantitative aspects of the effects of insulin, epidermal growth factor and dexamethasone on DNA synthesis in cultured adult rat hepatocytes
Authors: Sand Tor-Erik , Brønstad Gunnar , Digernes Vemund , Killi Anne , Amara Wasfiyeh , Refsnes Magne , Christoffersen Thoralf
Published: December 2008

Abstract. Epidermal growth factor (EGF) and insulin in combination have previously been shown to initiate S-phase in primary cultures of adult rat hepatocytes. We here describe the detailed time course and dosedependency of the effects of EGF and insulin on DNA synthesis in cultured hepatocytes. The DNA synthesis was assessed either biochemically or autoradiographically with a fairly good correlation between the two methods. DNA synthesis started 24–30 h after plating of the cells and peaked at approximately 70 h. Up to 70% of the cells entered DNA synthesis during this period. EGF and insulin acted synergistically on the DNA synthesis. Dexamethasone raised the DNA synthesis slightly, maximal effect occurred at concentrations above 2.5 nm and this agent was routinely used in the experiments with EGF and insulin. In the presence of 0.4 μm insulin from the time of plating, EGF dose-dependently increased the DNA synthesis with maximal effect at 5–15 nm. When added in combination with 1.7 nm EGF, insulin enhanced the DNA synthesis over the concentration range from 0.1 to 3 nm. These studies show that primary cultures of hepatocytes are useful in assessing the quantitative aspects of the interactions between the growth stimulating effects of hormones.
Multiple-sites of inhibition by intravenous metyrapone of human adrenal steroidogenesis
Authors: Schöneshöfer M. , Claus M.
Published: December 2008

Abstract. The in vivo influence of metyrapone on adrenal steroidogenesis has been studied by measuring plasma concentrations of pregnenolone, 17-OH-pregnenolone, progesterone, 17-OH-progesterone, 11-deoxycorticosterone, 11-deoxycortisol, corticosterone, cortisol, 18- OH -11- deoxycorticosterone, 18- OH -corticosterone and aldosterone before, during and after a 5 h infusion of metyrapone ditartrate at doses of 0.2 g/h and 0.8 g/h respectively. Time courses of plasma steroids and corticotrophin indicate an inhibitory effect of metyrapone on total adrenal steroidogenesis in addition to the known inhibition of the 11- and 18-monooxygenase. The effect on total adrenal steroidogenesis is pronounced at high concentrations of metyrapone and may be compensated by corticotrophin. This effect and a concomitant suppressive effect of metyrapone on plasma corticotrophin itself may account for the frequently described falsely abnormal responses to the metyrapone test. From the present 'in vivo' data, no significant, metyrapone induced alterations of the 3β-hydroxysteroid dehydrogenase/Δ5-isomerase, 17-monooxygenase, 21-monooxygenase or the 18-hydroxysteroid dehydrogenase are apparent.
Hormonal regulation of ascorbic acid in the adrenal of the rat
Authors: Overbeek G. A.
Published: December 2008

Abstract. Fifteen days after hypophysectomy of rats the concentrations of ascorbic acid (AA) in adrenals, liver, blood and urine are lower than in normal rats or in rats 1 day after hypophysectomy. Despite the low levels the percentage AA depletion after administration of ACTH and the subsequent repletion to the pre-ACTH level are normal.

Lack of corticosteroids is not the cause of the low AA levels, as shown by experiments in 15 days adrenalectomized rats and in rats treated with low doses of dexamethasone.

Fifteen days treatment with high doses of dexamethasone lowered the AA concentrations in adrenals, liver and blood. Treatment with long-acting ACTH maintained adrenal weight but not adrenal and blood AA. A high dose of ACTH lowered these levels. The administration of AA markedly increased the AA levels in blood, but did not normalize its concentration in the adrenals, not even when the size of the adrenals was maintained by treatment with long-acting ACTH. Growth hormone, in particular when administered together with long-acting ACTH, markedly raised the AA concentration in the adrenals but hardly affected the AA blood level. Rats with high blood levels of prolactin induced by pituitary grafts in the kidney also had clearly higher AA levels in adrenals, but not in blood.

These results indicate that, although acute AA release from the adrenal is caused by ACTH, AA uptake to a certain concentration is not controlled by the pituitary gland, and above this concentration is promoted by growth hormone and prolactin. In the liver AA release may also be caused by ACTH but the AA production is promoted by other as yet unidentified pituitary factors.
Cyproheptadine-mediated inhibition of growth hormone and prolactin release from pituitary adenoma cells of acromegaly and gigantism in culture
Authors: Ishibashi Miyuki , Fukushima Takanori , Yamaji Tohru
Published: December 2008

Abstract. The effect of cyproheptadine on growth hormone (GH) and prolactin (Prl) secretion from cultured pituitary adenoma cells of acromegaly and pituitary gigantism was studied. When varying doses of cyproheptadine ranging from 0.01 to 1 μm were added to the incubation media, GH secretion was consistently inhibited and a dose-response relationship was observed between the cyproheptadine concentrations and the amounts of GH released into the media. In pituitary adenomas which concurrently produced and secreted Prl, cyproheptadine likewise suppressed Prl release in a dose-related manner. This effect of cyproheptadine was not blocked by coincubation with serotonin. Similarly, coincubation with a dopaminergic antagonist, haloperidol, failed to reverse the inhibitory action produced by cyproheptadine. When coincubated with dopamine, cyproheptadine further inhibited GH and Prl secretion. These results suggest that cyproheptadine possesses a direct action on human somatotroph adenoma cells to inhibit GH and Prl secretion by an unknown mechanism that is different from serotonergic and dopaminergic systems.
Acquisition of urine, kidney and submandibular gland epidermal growth factor responsiveness to thyroxine administration in neonatal mice
Authors: Lakshmanan J. , Perheentupa J. , Macaso T. , Fisher D. A.
Published: December 2008

Abstract. Thyroxine (T4) administration to newborn mice on days 0–6 produced no measurable changes of submandibular gland (SMG) or kidney epidermal growth factor (EGF) concentrations on day 7, compared with vehicle-treated control pups. By contrast, this regimen caused a large increase in urine EGF levels. The effects of three T4 injection regimens (on days 0–6, 7–14 and 0–14) were then studied on day 15. The 0–14 and 7–14 day-regimens elicited large increments in urine, SMG and kidney EGF concentration, the 0–14 day-regimen having the greatest effect. The 0–6 day-regimen had no effect on SMG and kidney EGF concentrations on day 15 but did increase urine EGF. In summary, urine EGF responsiveness to T4 is present during the first week of life, but SMG and kidney EGF responsiveness develops only in the second week. Administration of T4 appears to accelerate the normal ontogeny of urine, kidney and SMG EGF.
Beta receptors in peripheral mononuclear cells increase acutely during exercise
Authors: Burman Kenneth D. , Ferguson Earl W. , Djuh Yin-Ying , Wartofsky Leonard , Latham Keith
Published: December 2008

Abstract. Five healthy adult well trained men (averaging 49 miles running per week) were exercised to exhaustion on a treadmill. Plasma epinephrine increased from 168 ± 37 pg/ml prior to exercise to 633 ± 155 pg/ml immediately after exercise (P < 0.025) and plasma norepinephrine increased from 1608 ± 345 to 8576 ± 1662 pg/ml (P < 0.025) in the two respective periods. Beta receptor density increased from 53 ± 18 fmol/mg protein before exercise, to 223 ± 63 fmol/mg (P < 0.05) protein immediately after exercise, and then decreased to 83 ± 27 fmol/mg protein 1 h later (P < 0.05 compared to postexercise). The mean Kd value prior to exercise of 1.5 ± 0.2 × 10−11 m was unchanged statistically throughout the study. Following correction for haemodilution, serum total and free T4 and T3 concentrations were also unchanged during exercise, although reverse T3 levels did increase from 39 ± 4 to 45 ± 0 ng/dl (P < 0.05).

These findings suggest that: 1) plasma epinephrine, norepinephrine and beta receptor density, but not Kd, increase acutely during exercise and 2) total and free
Increased triglyceride secretion rate and hyperinsulinaemia in ventromedial hypothalamic lesioned rats in vivo
Authors: Satoh Shinobu , Inoue Shuji , Egawa Masato , Takamura Yutaro , Murase Toshio
Published: December 2008

Abstract. The present study aimed to measure triglyceride secretion rate (TGSR) into the circulation in ventromedial hypothalamic (VMH) lesioned rats. Average gain of body weight in VMH lesioned rats was 72 ± 6 g (mean ± se, n = 9) in a week; significantly greater than that in controls (6 ± 2, n = 8, P < 0.001). TGSR was determined under hexobarbital anaesthesia in fasted rats by measuring the increase in plasma concentration after the triglyceride removal mechanism was blocked by injecting Triton WR-1339. TGSR in VMH lesioned rats was 500 ± 37 mg/dl of plasma/h; markedly higher than that in controls (239 ± 12, P < 0.001). Serum insulin concentration in VMH lesioned rats was 2.26 ± 0.32 ng/ml; significantly higher than that in controls (0.83 ± 0.08, P < 0.001). There was a positive correlation between serum insulin concentration and TGSR in VMH lesioned rats (r = 0.709, P < 0.05). The increased secretion rate of triglyceride in VMH lesioned rats is discussed in connection with the development of obesity in these rats.
Decrease of LRH receptors in the pituitary gland in streptozotocin-induced diabetic rats
Authors: Tasaka Keiichi , Terakawa Naoki , Shimizu Ikuya , Ohtsuka Shirou , Miyake Akira , Aono Toshihiro
Published: December 2008

Abstract. In studies into the mechanism of anovulation in the diabetic condition, the LRH receptor content of the pituitary gland of rats with diabetes mellitus was determined. Normal female rats weighing 180–200 g were injected iv with either streptozotocin (6 mg/100 g body weight) or vehicle in dioestrus of the oestrous cycle. The rats were sacrificed by decapitation 9 days after treatment, and serum LH concentrations and the LRH content of the medial basal hypothalamus (MBH) were measured by radioimmunoassay (RIA), and the LRH receptor content of the pituitary gland was determined.

The serum concentration of LH and the LRH content of the MBH in diabetic rats were 34.4 ± 4.8 ng/ml (mean ± sem) and 2.05 ± 0.04 ng/MBH, respectively, which were similar to the respective values of normal rats in dioestrus. However, the LRH receptor content of diabetic rats (13.2 ± 3.9 fmol/pituitary) was significantly (P < 0.05) lower than that of normal rats in dioestrus (68.0 ± 7.1 fmol/pituitary) and pro-oestrus (59.4 ± 13.6 fmol/pituitary).

These results suggest that anovulation in diabetic rats is at least partly attributable to a low content of LRH receptors in the pituitary gland.
Post-natal thyroid function in low birth weight infants; a longitudinal assessment of free thyroxine and thyroid hormone binding globulin
Authors: Hirano Takeki , Singh Jaideep , Srinivasan Gopal , Pildes Rosita
Published: December 2008

Abstract. Because the concentrations of serum free thyroxine (FT4) and thyroid hormone binding globulin (TBG) have not been fully evaluated in preterm infants at the immediate post-natal period, we studied the longitudinal changes of serum FT4 and TBG, along with thyroxine (T4) and thyroid stimulating hormone (TSH), at birth (cord blood), 2 days, 1 week and 2 weeks of age in 7 infants with birth body weight ≦ 1000 g, 7 infants with body weight 1001 to 1350 g, 11 infants with body weight 1351 to 2499 g, and 11 full-term infants. Free T4 concentrations were measured by Corning Medical radio-immunoassay (RIA) kit.

The infants with extremely low birth weight (ELBW) (body weight ≦ 1000 g) showed precipitous declines of total T4 and, to a lesser extent, of FT4 concentrations at 1 and 2 weeks of age. These post-natal T4 and FT4 decreases in ELBW neonates have not previously been reported. The clinical significance of this finding remains, speculative, but it may be due to metabolic or nutritional problems related to extreme prematurity itself.

This study suggests that measurement of FT4 is a useful adjunct to the assessment of ELBW infants with wery low T4 values, if done between 1 to 2 weeks af age, and could be used as a primary hypothyroid screening tool instead of T4 measurements, provided that an FT4 assay is developed that uses the elute of blood spotted on filter paper.
Ontogeny of thyrotrophin concentration in perinatal rats
Authors: Fukiishi Yonetaka , Hasegawa Yasuhiko
Published: December 2008

Abstract. Negative feedback control by triiodothyronine (T3) of thyrotrophin (TSH) secretion from rat pituitary glands was studied during the perinatal period of rat development. Foetal serum TSH concentration declined significantly between 20 and 21 days of gestation, reached a low level at delivery, and remained low for several days after birth. T3 suppressed serum TSH concentration in a dose-responsive manner when given to foetuses on day 20 of gestation at 0.13 to 2.0 μg/100 g body weight of the estimated body weight. The responses of serum TSH levels and thyroid weights to PTU treatments differed with gestational age. We conclude that negative feedback control by T3 of serum TSH concentration exists in rat foetuses as early as day 20 of gestation and differs from that found in adult rats.
Adaptation to phosphorus depletion: effect of streptozotocin-induced diabetes mellitus
Authors: Kawanobe Yumiko , Matsumoto Toshio , Takano Kazue , Ezawa Ikuko , Ogata Etsuro
Published: December 2008

Abstract. The effect of streptozotocin-induced diabetes mellitus (DM) on the adaptive response to phosphorus depletion (PD) was investigated in order to examine if DM has any influence on the adaptation to PD in rats. PD for 7 days caused a marked reduction in serum phosphate (Pi) levels and increase in serum calcium (Ca) concentrations in control rats. In contrast, the increase in serum Ca concentration caused by PD was almost entirely eliminated in DM rats. Similarly, while bone Ca and P content was decreased by 7 days of PD in control rats, no significant changes in bone mineral contents were observed in DM rats during PD. There was a marked reduction in fractional excretion of Pi and an increase in fractional excretion of Ca during PD in both control and DM rats. Serum somatomedin A levels measured by radioreceptor assay were lower in DM rats compared to those in control rats, but PD caused no significant changes in either group of animals. These results demonstrate that the development of hypercalcaemia and reduction in bone mineral content in respone to PD were inhibited while the renal tubular responses to PD were not affected in DM rats. It is suggested that the inhibition of the hypercalcaemic response to PD in DM rats is mainly due to an inhibition of the resorptive response of bone to PD, and that insulin either directly or indirectly may play a permissive role in the development of the resorptive response of bone to PD.
Regulation of (Ca2+-Mg2+)-ATPase activity by calcitonin binding to rat liver plasma membranes
Authors: Yamaguchi Masayoshi , Ito Michiyo
Published: December 2008

Abstract. The plasma membranes isolated from rat liver bound 125I-labelled ([125I]) synthetic [Asu1,7]eel calcitonin (CT), with increasing concentrations of [125I]CT. This specific binding was completely saturated at a concentration of 0.5 nm CT. A high affinity Ca2+ -stimulated, Mg2+-dependent ATPase [(Ca2+-Mg2+)-ATPase] activity in the plasma membranes was significantly decreased by the presence of a very low concentration of CT (7.4 pm), although the hormone did not affect the activity of the plasma membrane 5′-nucleotidase. The concentration of CT needed for maximal inhibition of (Ca2+-Mg2+)-ATPase in the plasma membranes was less than 0.74 nm. The plasma membranes washed with 10−3% digitonin did not show an inhibitory effect of CT on (Ca2+-Mg2+)-ATPase activity, while the reagent did not have a significant effect on the enzyme. These results suggest that the inhibition of (Ca2+-Mg2+)-ATPase activity maybe part of the mechanism by which CT elevates cytosolic Ca2+ in liver cells.
Serotonergic regulation of prolactin and growth hormone secretion in man
Authors: Lewis David A. , Sherman Barry M.
Published: December 2008

Abstract. Controversy still exists regarding the role of serotonin in the regulation of prolactin (Prl) and growth hormone (GH) secretion in man. We gave healthy male volunteers three oral doses (0.5, 1.0 and 1.5 mg/kg) of fenfluramine, a serotonin-releasing agent and uptake inhibitor, and a corresponding placebo. There was a significant dose-response effect of fenfluramine on Prl but not on GH levels. Following the highest dose of fenfluramine, mean Prl levels increased from 9.7 ng/ml to 42.3 ng/ml.

In a separate study, subjects were pre-treated with cyproheptadine, a serotonin antagonist, before the administration of fenfluramine. Cyprohaptadine did not significantly affect basal Prl or GH levels, but it did blunt the response of Prl to fenfluramine. Cyproheptadine pretreatment did not alter plasma levels of fenfluramine.

Our findings support a stimulatory role for serotonin in the regulation of Prl secretion in man. They also suggest that serotonin does not have a major influence on GH secretion in man.
Effects of a 72-hour prostacyclin infusion on the hormone levels in patients with obliterative arterial disease
Authors: Irsy G. , Blaskó Gy. , Góth M. , Szabolcs I. , Gachályi B. , Szilágyi G.
Published: December 2008

Abstract. Effects of a 72-h prostacyclin (PGI2) infusion (5 ng/kg/min) on hormone levels were studied in 11 patients (5 males, 6 females) suffering from obliterative arterial disease of the lower extremities. ACTH, cortisol, TSH, prolactin (Prl), GH, LH, FSH, T3, T4, calcitonin, parathyroid hormone (PTH), insulin, plasma renin activity (PRA), aldosterone and testosterone levels were measured at −15, 0, 30, 120, 240 min and 24, 48, 72 and 96 h after the infusion. During the first 240 min Prl and GH levels showed an increase that was thought to be either an effect of release of hormones or a consequence of stress. At the same time the thyroid hormones, T3, T4 and calcitonin decreased, presumably owing to an alteration in the blood flow to the thyroid gland. All these hormone levels returned to normal at 24 h in spite of the infusion continuing. PRA increased only during the second half of the infusion. No changes were found in the levels of ACTH, cortisol, TSH, LH, FSH, PTH, insulin, aldosterone and testosterone during the infusion. Five diabetics showed the same hormonal changes as the non-diabetics and their blood sugar levels remained unaffected during and after the procedure.
Cyclic Cushing's syndrome combined with cortisol suppressible, dexamethasone non-suppressible ACTH secretion: a new variant of Cushing's syndrome
Authors: Schweikert Hans-Udo , Fehm Horst Lorenz , Fahlbusch Rudolf , Martin Rainer , Kolloch Rainer , Higuchi Miyoko , Krück Friedrich
Published: December 2008

Abstract. A 55 year old woman with an unusual form of Cushing's disease was studied. During several periods (periods lasting up to 84 days) evidence of cortisol hypersecretion with cycles occurring every 6 days was found. Suppression of plasma cortisol through orally administered dexamethasone (up to 32 mg per day) could not be achieved either during periods of cyclic cortisol hypersecretion or during apparent remission with normal cortisol secretion. Marked suppression of plasma ACTH was measured in response to an iv infusion of 50 mg cortisol over a period of 55 min whereas a similar test with 2 mg dexamethasone (iv bolus) did not suppress ACTH secretion. Transsphenoidal exploration of the sella revealed a tumour surrounding the anterior pituitary. Examination of the pituitary showed a few tiny tumour structures embedded in normal tissue which could not be removed, when the tumour was resected selectively under preservation of normal appearing tissue. Post-operatively, clinical and chemical remission (normal response to 1 mg dexamethasone) was observed for about 4 months. Thereafter, cortisol hypersecretion occurred again necessitating bilateral adrenalectomy.

Our results are compatible with the assumption that normal hypothalamic-pituitary-adrenal suppressibility with cortisol, but not with dexamethasone, was caused by the loss of feedback receptors for dexamethasone in the presence of cortisol receptors in the cells which secrete ACTH or CRF.

The combination of cyclic hypercortisolism with dexamethasone non-suppressible Cushing's syndrome has not been reported before and thus represents a new variant of Cushing's syndrome.
The luteinizing hormone response to luteinizing hormone-releasing hormone, prostaglandin E2 and naloxone is modulated by divergent sensitivity to testosterone feedback
Authors: Schweiger Ulrich , Pirke Karl Martin
Published: December 2008

Abstract. Testosterone (T) levels necessary to suppress LH secretion are reduced in starvation, and increased feedback sensitivity to T is therefore postulated. The luteinizing hormone (LH) response to naloxone (Nal) is more easily suppressed by starvation than is its response to prostaglandin E2 (PGE2) and to luteinzing hormonereleasing hormone (LRH). If the divergent suppressibility is due to altered feedback sensitivity in starvation, it should be feasible to reproduce this phenomenon in normally nourished rats by increasing T levels. Adult male Wistar rats were castrated and implanted with silicone capsules (0–2.6 cm) filled with T. Indwelling jugular cannulae were implanted. On days 4 to 8 post operation rats were injected iv with LRH (25–400 ng/kg body weight), PGE2 (0.05–1.0 mg/kg body weight) or Nal (0.5–50 mg/kg body weight). Blood samples were drawn before and 10, 20 and 30 min after injection. Results show that the response to Nal was already suppressed at medium T levels. The LH response to PGE2 was diminished to a greater extent than the response to LRH but was never completely suppressed by increasing steroid levels. These data are compatible with the hypothesis that steroid feedback sensitivity augments with increasing levels of regulation of the hypothalamic-pituitary-gonadal axis.
Contribution to the aetiology of diabetes insipidus: Yersinia pseudotuberculosis infection
Authors: Massol J. , Humbert Ph. , Semon C. , Fellmann D.
Published: December 2008

Abstract. A case concerning a young man presenting with polyuria and polydipsia which were preceded 1 month earlier by a febrile enteritis is reported.

The role of Yersinia pseudotuberculosis in diabetes insipidus of this type is discussed on the basis of clinical, biological and evolutional criteria.
Serum free thyroxine in patients with T3-toxicosis
Authors: Martino Enio , Pacchiarotti Alessandro , Aghini-Lombardi Fabrizio , Grasso Lucia , Bambini Giovanni , Baschieri Lidio , Pinchera Aldo
Published: December 2008

Abstract. The serum free thyroxine concentration was measured by direct radioimmunoassay in 38 untreated T3-thyrotoxic patients with elevated serum total and free triiodothyronine, normal serum thyroxine and free thyroxine index, no TSH response to TRH, and with clinical evidence of hyperthyroidism. An elevation of circulating free thyroxine values was observed in 58% of the patients, whereas total serum thyroxine concentration was within the normal range. It is suggested, therefore, that T3-thyrotoxicosis should be reserved for patients with elevated serum total T3 and free T3 concentrations and normal serum total T4 and free T4 concentrations. Serum thyroxine-binding globulin concentrations were significantly lower (P < 0.025) in patients with an elevated serum free thyroxine (18.7 ± 3.6 μg/ml: mean ± sd) as compared with those in patients with a normal free thyroxine concentration (23.4 ± 2.6 μg/ml). In addition, no daily fluctuations in total and free thyroxine concentration were observed in 6 patients over a 4–8 day period.
Plasma free and total iodothyronine levels in hypophysectomized and intact lamb foetuses during the last third of gestation
Authors: Wrutniak Chantal , Cabello Gérard , Bosc Michel
Published: December 2008

Abstract. The changes in plasma levels of thyroxine (T4), free thyroxine (free T4), triiodothyronine (T3), free triiodothyronine (free T3), and reverse triiodothyronine (rT3) were observed in intact or hypophysectomized lamb foetuses during the last third of gestation. Hypophysectomy was performed at two stages: 100 and 120 days of gestation. Cord blood was collected after Caesarean section.

In intact foetuses, T4 and free T4 levels increased significantly between day 100 and 120 of gestation, but decreased from day 132 to birth. T3 levels, low until day 132, rose abruptly during the last 12 days of gestation, as did the T3/free T4 ratio. Free T3 levels, relatively high on day 100, decreased until day 130 to rise during the last days of gestation. Reverse T3 levels, high since day 100, increased sharply until day 132 as did the reverse T3/free T4 ratio, and then declined. In hypophysectomized foetuses, undetectable or very low levels of T4, free T4 and rT3 were observed on day 120 and 144. T3 levels, although decreased by pituitary destruction, remained at 39.7% (120 days) and 21.4% (144 days) of the values recorded in intact foetuses. Free T3 levels, normally depressed at the end of gestation, were not affected by hypophysectomy on day 120. When hypophysectomy was performed later, the levels of T4, free T4 and rT3 were slightly increased on day 144 as compared with those of the other hypophysectomized foetuses.

This study confirms the changes in the plasma iodothyronine levels observed previously in the lamb foetus. Moreover, it appears that T4 thyroid secretion depends almost exclusively on foetal pituitary function, and that if the sheep placenta is impermeable to T4 and rT3, a significant transfer of maternal T3 can occur.
Effect of gonadotrophins on progesterone secretion by cultured granulosa cells obtained from human preovulatory follicles
Authors: Hillensjö T. , Sjögren A. , Strander B. , Nilsson L. , Wikland M. , Hamberger L. , Roos P.
Published: December 2008

Abstract. Granulosa cells were obtained from human preovulatory follicles in 31 women undergoing in vitro fertilization and embryo transfer due to tubal infertility. Follicular maturation was stimulated and synchronized by treatment with Clomiphene or human menopausal gonadotrophin (hMG), or both, plus human chorionic gonadotrophin (hCG). Follicles were aspirated by ultrasound guided puncture approximately 34–36 h after the hCG injection.

The granulosa cells were washed and suspended in modified medium 199 containing 10% foetal bovine serum and cultured as monolayers for 6–8 days in the absence and presence of hormones and reactants. Progesterone formation was analyzed by RIA. In general, the cells underwent morphological luteinization and secreted high amount of progesterone. Under basal conditions the secretion of progesterone was highest during the first 2 days in culture and then gradually declined. Progesterone secretion was stimulated by human LH, hCG and the adenylate cyclase stimulator forskolin, with a maximal effect between days 2–6. The β-adrenergic agonist isoproteronol in preliminary experiments potentiated the stimulatory effect of hCG but had no own stimulatory effect. No clear differences in progesterone secretion or responsiveness to in vitro stimulation relating to the various in vivo stimulation protocols were found.
Treatment of human hyperprolactinaemia with a new dopamine agonist: CU 32085 (mesulergin)
Authors: Dewailly D. , Thomas P. , Buvat J. , Wemeau J. L. , Fourlinnie J. C. , Lemaitre G. , Mazzuca M. , Fossati P.
Published: December 2008

Abstract. CU 38085 (mesulergin) was given at doses ranging from 0.5 to 5 mg/day to 37 patients with pathological hyperprolactinaemia of varying aetiology. The effectiveness of this drug on the suppression of hyperprolactinaemia and on the recovery of gonadal functions was equivalent to that of bromocriptine previously given to a different group of 83 hyperprolactinaemic patients. Tumour shrinkage during treatment with CU 32085 was ascertained in two cases of macroprolactinoma. Histological examination after adenomectomy revealed extensive peri-vascular fibrosis in both cases. In most patients, the efficient doses of CU 32085 were 5-fold lower than those of bromocriptine. After acute oral administration in 10 previously untreated patients, 0.5 mg of CU 32085 had a more prolonged suppressive effect on Prl levels than 2.5 mg of bromocriptine (approximately 18 vs 12 h). According to this, 0.5 mg CU 32085 once a day was sufficient to maintain Prl levels within the normal range in 16 patients. Side-effects were similar in nature and frequency to those induced by bromocriptine and seemed to be dose-dependent. They can be avoided by slowly increases of dose at initiation of treatment.
Reproductive endocrine effects of intranasal administration of progesterone to adult female rhesus monkeys
Authors: David G. F. X. , Puri V. , Dubey A. K. , Puri C. P. , Kumar T. C. Anand
Published: December 2008

Abstract. Adult female rhesus monkeys exhibiting normal ovulatory menstrual cycles were treated with progesterone nasal sprays. Animals in group A (n = 9) were treated with the solvent only (controls). Animals in groups B (n = 6), C (n = 17) and D (n = 7), respectively, were treated with a daily dose of 0.4, 2 and 10 μg of progesterone and the spraying was done between days 5–14 of the cycle. Ovulation was monitored by laparoscopy on day 20. The serum endocrine profile throughout the treated menstrual cycle was studied with respect to oestradiol and progesterone. Bioactive luteinizing hormone (bLH) was studied in blood samples taken on the day of the mid-cycle oestradiol peak, 2 days before, and 2 days after. The menstrual cycle was divided into two phases with respect to the mid-cycle oestradiol peak: phase I was taken to include day 1 of the cycle to the day of the oestradiol peak, and the remaining part of the menstrual cycle was considered to be phase II.

The serum-endocrine profile in the controls was similar to that observed in normal ovulatory menstrual cycles. However, in the progesterone-treated groups three types of menstrual cycles were discernable on the basis of the serum endocrine profile. In the type I menstrual cycle, observed only in group C (n = 10), the mid-cycle bLH peak was abolished and the progesterone levels remained low throughout the cycle. Laparoscopy revealed these to be anovulatory cycles. In the type II menstrual cycle, seen in the 3 animals of group B, 2 animals of group C, and in all the 7 animals of group D, the mid-cycle bLH peak was abolished and the progesterone levels during phase II of the cycle were significantly lower than in the controls, indicative of poor luteal function. In the type III menstrual cycle seen in the remaining monkeys, the serum endocrine profile did not differ from that seen in the controls. Thus, the present studies indicate that the intranasal administration of progesterone shows a dose-response effect with respect to the suppression of the oestradiol induced mid-cycle surge of bLH. Suppression of the mid-cycle bLH peak resulted in anovulatory cycles or ovulatory cycles with poor luteal function.
Effect of prolonged dopamine receptor blockade on lactotroph activity in the rat pituitary gland
Authors: Prysor-Jones R. A. , Silverlight J.J. , Jenkins J. S.
Published: December 2008

Abstract. The dopamine antagonist fluphenazine was administered to young rats in the presence or absence of physiological concentrations of oestradiol for periods of 230 days.

An important observation arising from the investigation was that no pituitary tumours were produced by the combination of prolonged dopamine receptor blockade and small amounts of oestradiol.

Prolactin (Prl) secretion increased rapidly with fluphenazine but in the absence of oestrogen lactotroph activity subsequently declined after 20 days and this decrease in hormone secretion was accompanied by a greatly increased dopamine turnover in the medio-basal hypothalamus. In contrast, small amounts of oestradiol modified the effect of fluphenazine alone causing a greatly increased secretion of Prl for a much larger period and a reduction in the dopamine content of the hypothalamus. This combination also doubled the synthesis of DNA by the pituitary compared with controls, and electron microscopy revealed evidence of increased secretory activity of the lactotrophs in the presence of both fluphenazine and oestrogen but not in those animals treated with fluphenazine only.

Towards the end of the experiment Prl values declined even in the presence of oestrogen and increasing the dose of fluphenazine had no significant effect. It was suggested that eventually there may be a direct inhibitory action of the dopamine antagonist on the lactotrophs.
How to deal with undetectable and low measurable serum thyroglobulin levels in the follow-up of patients with differentiated thyroid carcinoma?
Authors: Välimäki Matti , Lamberg Bror-Axel
Published: December 2008

Abstract. Serum thyroglobulin (Tg) was measured in 52 patients 3 months to 15 years (mean 5.3 years) after thyroidectomy with or without subsequent radioablation for differentiated thyroid carcinoma, before and after the interruption of suppressive thyroxine (T4) replacement therapy for 5 weeks. Whole body scintigraphy was carried out at the end of the T4 withdrawal period.

Serum Tg was undetectable (< 3 μg/l) in 38 patients on T4 therapy, in 18 the scintigraphy showed a minimal accumulation in the neck region and in 20 no uptake anywhere after withdrawal of T4. In the former group Tg rose in 10 patients to 4–21 μg/l when off T4 which seemed to correspond to the normal tissue left in situ, in the latter group Tg rose only in 2 patients to 5 and 21 μg/l, respectively. Two patients out of 14 with detectable Tg on T4 had pulmonary metastases as uncovered by whole body scintigraphy (in one of them Tg rose from 12 μg/l on T4 to 1200 μg/l off T4) and 6 patients were suspected for having recidual cancer tissue (2 patients had a negative scintigraphy) because the Tg rose (66– 215 μg/l) over the upper limit of the reference range (< 50 μg/l) after T4 withdrawal.

In conclusion, in the follow-up of patients with differentiated thyroid carcinoma no routine scans are needed as long as serum Tg remains undetectable but further examinations are shortly warranted when detectable Tg is obtained during T4 suppression.
Treatment of severe Graves' ophthalmopathy with cyclosporin A
Authors: Utech C. , Wulle K. G. , Bieler E. U. , Pfannenstiel P. , Panitz N. , Kiefer H.
Published: December 2008

Abstract. Ten patients with severe Graves' ophthalmopathy, resistant to other therapeutic regimens were treated with cyclosporin A (CyA) over a period of 6 months. Clinically, 9 patients improved, 2 of them only after addition of corticosteroids. Intra-ocular tension on upward gaze decreased in all of these 9 patients (P < 0.01). In 6 patients there was a significant decrease in eye muscle thickness under the treatment (P < 0.05) as determined by computerized tomography.

Side effects (e.g., paraesthesia, proteinuria) which were observed under higher doses of CyA, disappeared after lowering the dose. In only one out of 3 patients with hypertension an antihypertensive medication became necessary.

CyA appears to be a valuable drug for treatment of severe Graves' ophthalmopathy when previous therapeutic regimens turned out to be unsuccessful.
Kinetics of [123I]iodide uptake and discharge by perchlorate in studies of inhibition of iodide binding by antithyroid drugs
Authors: McCruden D. C. , Hilditch T. E. , Connell J. M. C. , Alexander W. D.
Published: December 2008

Abstract. Thyroidal binding of idoide was studied by kinetic analysis of [123I]iodide uptake and its discharge by perchlorate in 80 hyperthyroid subjects receiving antithyroid drug therapy. Five dosage regimens ranging from 5 mg carbimazole twice daily to 15 mg methimazole twice daily were studied. Binding inhibition was estimated at 5–7 h after drug as an index of the mean effect of the 12 hourly regimen. In all cases, except one in the lowest dose group, binding was found to be markedly reduced with mean binding rates ranging from 0.002 to 0.020 min−1 (normal > 0.15 min−1). The net clearance of iodide in the lowest dose group was reduced to a mean value near the upper limit of the euthyroid range, whereas in the highest dose group it lay at the lower limit of the euthyroid range. These results were reflected in the serum thyroid hormone response. There was a reducing incidence of inadequate control of hyperthyroidism and an increasing incidence of hypothyroidism with increasing thiourylene dose. The exit rate constant of free iodide for the various doses showed values from 0.048 to 0.055 min−1. Corresponding mean values for the discharge rate constant after perchlorate were 0.087 to 0.105 min−1. This suggests that perchlorate increases the rate of iodide release from the thyroid gland. Studies at a later interval after drug (12–14 h) showed no change in discharge rate constant. This leads to the conclusion that perchlorate may further inhibit iodide binding in subjects receiving antithyroid drug therapy.
Dissociation of the triiodothyronine receptor from the nucleus induced by cations: evidence for divalent cation sensitive and insensitive nuclear sites
Authors: Bernal Juan , Perez-Castillo Ana
Published: December 2008

Abstract. Aliquots of purified rat liver nuclei were diluted at 0°C in isotonic buffers containing monovalent (Na+) or divalent (Ca2, Mg2+) cations. At different times following dilution the nuclear suspensions were centrifuged and the T3 receptor was measured in KCl extracts of the nuclear pellets. The rate of receptor loss after dilution in EDTA was 0.0025 min−1. Dilution in the presence of cations caused a fast release of receptor during the first 10 min. This phase, which was not observed when the nuclei were diluted in EDTA without salt, was followed by a second phase where the receptor was released at the same rate as in EDTA. Receptor release was only dependent on the presence of cations in the dilution buffer during the first 10 min after dilution. The amounts of receptor remaining in the nuclei after the first 10 min of dilution were 51.8 ± 9.2%, in the presence of Ca2+and Mg2+, 38.6 ±8.9% in 0.15 m NaCl, and 18.0 ± 4.8% in 0.15 m NaCl in the presence of Ca2+ and Mg2+. The release of receptor was not influenced by the integrity of the nuclear membrane.

These results suggest the presence of divalent cation sensitive and insensitive nuclear sites for the T3 receptor, in amounts which could be estimated to be about 48 and 52%, respectively. Other interpretations are also possible, such as the presence of a high proportion of free receptors in the nucleosol, which could be released during the first phase of dilution if the negative charges in chromatin are blocked by cations to avoid redistribution of receptors immediately after dilution.
Dynamic evaluation of prolactin secretion by successive TRH and metoclopramide stimulations
Authors: Kauppila Antti , Heikkinen Jorma , Viinikka Lasse
Published: December 2008

Abstract. We evaluated the clinical applicability of a 2-h test in which the prolactin (Prl) responses to thyrotrophin releasing hormone (TRH) (200 μg iv) and the dopamine antagonist, metoclopramide (MC; 10 mg iv) were studied successively, 1 h apart. Nine healthy women were studied with TRH-MC test and with another test in which MC alone was used or the drugs were given in opposite order. The preceding TRH injection did not affect the Prl responses to MC, nor did preceding MC affect the Prl response to TRH.

With the TRH-MC test, Prl responses to TRH and MC were significantly lowered in amenorrhoea (N = 8) and hyperprolactinaemia (N = 15) regardless of whether or not treated with bromocriptine, and to MC only in oligomenorrhoea (n = 11). In normoprolactinaemic galactorrhoea (N = 7) the responses were similar as in healthy women. The ratio between Prl responses to TRH and MC was significantly higher in women with bromocriptine-treated hyperprolactinaemia (1.06 ± 0.8, so) than in healthy controls (0.34 ± 0.13).

The capacity of pituitary lactotrophs to secrete Prl in response TRH and MC can be evaluated with a 2-h test which has potential for investigation of pituitary Prl dynamics in gynaecological endocrine disorders, particularly in amenorrhoea and hyperprolactinaemia.
Goitre size and outcome of medical treatment of Graves' disease
Authors: Laurberg Peter , Hansen Poul Erik Buchholtz , Iversen Eigil , Jensen Sigurd Eskjær , Weeke Jørgen
Published: December 2008

Abstract. One hundred and twenty-four patients with newly diagnosed hyperthyroidism received a combined thionamid-thyroxine medical therapy for approximately 2 years. According to the estimated goitre size before therapy and the type of goitre the patients were divided into 4 groups: Graves' disease no goitre (n = 19). Graves' disease small goitre (n = 57), Graves' disease medium or large goitre (n = 23), multinodular goitre (n = 25). The median follow-up period after cessation of medication was 64 (range 11–141) months.

The remission rates in the different groups during follow-up were calculated using life table analysis. Graves' patients with no goitre or a small goitre had a significantly better outcome (remission % after 5 years 82.5 ± 15.4 (se) and 71.5 ± 7.8, respectively) than Graves' patients with a medium size or large goitre (remission % after 5 years 37.0 ± 11.1) (P <0.025). Most patients with multinodular goitre had a relapse within the first year after stop of medication (remission % after 5 years 15.5 ± 10.1). Hence patients with Graves' disease having a small thyroid gland should be treated medically while surgery or radioiodine may be a more reasonable choice in Graves' patients with medium size or large goitres. Medically treated patients with toxic multinodular goitres have a very small chance of prolonged remission if medication is stopped.
Sex steroids and steroid binding proteins in female alcoholic liver disease
Authors: Carlström Kjell , Eriksson Sten , Rannevik Gunnar
Published: December 2008

Abstract. Blood levels of sex steroids and steroid binding proteins were measured in 21 females with alcoholic liver disease and in age matched healthy controls and correlated to type and severity of histological changes in concomitant liver biopsies. In patients with liver disease androstenedione levels were high in contrast to the low levels of dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS) and albumin. Normal levels of testosterone and total oestrone were found in the patients. SHBG varied independently of albumin and decreased SHBG levels were found in patients with steatosis. DHA, DHAS and albumin levels were negatively correlated to the total biopsy score and a positive correlation was found between DHAS and albumin. The higher levels of androstenedione were found in patients with mild histological lesions. The findings are thought to reflect alcohol-induced changes in hepatic as well as in adrenocortical activity.
Plasma adrenocorticotrophin, cortisol and aldosterone responses to ovine corticotrophin-releasing factor and vasopressin in sheep
Authors: Pradier P. , Davicco M. J. , Safwate A. , Tournaire C. , Dalle M. , Barler J. P. , Delost P.
Published: December 2008

Abstract. Ovine corticotrophin-releasing factor (oCRF) (1 μg/kg) and arginine vasopressin (AVP) (1 μg/kg) were injected iv in sheep, both separately and in combination. Plasma levels of immunoreactive ACTH (IRACTH), cortisol, and aldosterone were measured for 3 h after the injections. Mean levels before injections were 8 ± 4 pmol/l for ACTH, 7 ± 3 nmol/l for cortisol, and 28 ± 9 pmol/l for aldosterone. CRF caused a rapid rise in IR-ACTH and a peak level of 125 ± 52 pmol/l was obtained 15 min after injection. Highest values for cortisol and aldosterone levels were 40 ± 9 nmol/l and 64 ± 13 pmol/l, respectively, 30 min after injection. AVP also increased IR-ACTH (maximum level: 202 ± 77 pmol/l at 5 min) and aldosterone (128 ± 36 pmol/l at 15 min), whereas the cortisol increase was lower than after CRF. Simultaneous injection of CRF and AVP produced an addition of the IR-ACTH response (295 ± 82 pmol/l at 15 min), but the changes in cortisol levels were similar to those obtained after CRF alone and those in aldosterone levels resembled those induced by AVP alone.

Plasma Na and K, osmolality, and plasma renin activity (PRA) were not modified by either CRF or AVP. It is suggested that the increase in aldosterone levels after CRF could be mediated by ACTH and that after AVP by an IR-ACTH peptide with less effect on cortisol secretion.
Effects of prolactin administration on the zona glomerulosa of the rat adrenal cortex: stereology and plasma hormone concentrations
Authors: Mazzocchi Giuseppina , Robba Claudia , Rebuffat Piera , Nussdorfer Gastone G.
Published: December 2008

Abstract. The effects of short and prolonged treatments with prolactin on the morphology and hormone secretion of the rat adrenal zona glomerulosa were investigated by coupled morphometric and radioimmunological techniques. Short-term prolactin administration did not alter plasma aldosterone concentration or zona glomerulosa morphology. Conversely, chronic prolactin treatment caused both a notable hypertrophy of zona glomerulosa cells and a significant rise in the blood level of aldosterone. The possibility is discussed that prolactin may be involved in the control of the growth and steroidogenic capacity of the rat adrenal zona glomerulosa.