bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of human amniotic phospholipase A2 activity by steroid-sulphate derived from the foeto-placental unit
Authors: Saitoh Hiroshi , Hirato Kumiko , Tahara Ryuzo , Ogawa Koichi , Noguchi Yusei , Yanaihara Takumi , Nakayama Tetsuya
Published: December 2008

Abstract. To study the control of production of prostaglandins (PG) during pregnancy and parturition, amniotic membranes obtained from normal vaginal delivery were incubated with the substrate of phosphatidylcholine containing [14C]arachidonic acid in the Sn-2 position. Phospholipase A2 activity was calculated as the rate of release of [14C]arachidonic acid from the substrate. Various steroids were added to the incubation medium to elucidate the effect of steroids on the enzymatic activity. The addition of dehydroepiandrosterone-sulphate (DHA-sulphate) to the medium increased by 7-fold the rate of [14C]arachidonic acid release from phosphatidylcholine at a concentration of 1.67 mm. The enhanced rate of arachidonic acid release suggests that DHA-sulphate stimulates phospholipase A2 activity. The same amounts of pregnenolone-sulphate and oestrone-sulphate also enhanced the enzymatic activity, while cholesterol-sulphate, free steroids such as DHA, progesterone, cortisol and oestrogens revealed no effect. These results suggest that steroid sulphates may be involved in the regulatory mechanism for PG synthesis in amniotic membrane.
Danazol and prolactin status in patients with endometriosis
Authors: Wallace A. M. , Lees D. A. R. , Roberts A. D. G. , Gray C. E. , McLaren E. H. , Low R. A. L.
Published: December 2008

Abstract. A group of 55 women with endometriosis was studied before and during danazol therapy. An unexpectedly high proportion (36%) had a raised serum prolactin level before treatment which was reduced after 50 days of danazol (before treatment 783 ± 333 mU/l; on danazol 243 ± 113 mU/l, P < 0.001). In contrast patients with normal serum prolactin levels showed no significant drop on danazol therapy. In all patients serum oestradiol was significantly reduced during treatment (before treatment 449 ± 188 pmol/l; on danazol 207 ± 117 pmol/l, P < 0.001). In one patient with hyperprolactinaemia danazol reduced both basal and stimulated prolactin levels, whereas in 5 women with normal prolactin levels we could detect no gross alteration in metoclopramide or TRH stimulated prolactin levels associated with danazol therapy.

The possibility that normalisation of raised prolactin levels may be secondary to reduced oestrogens and that patients with endometriosis have an increased sensitivity to oestrogen-induced prolactin secretion is discussed.
Possible altered dopaminergic modulation of pituitary function in normal-menstruating women with insulin dependent diabetes mellitus (IDDM)
Authors: Djursing Henning , Carstensen Lisbeth , Hagen Claus , Andersen Anders Nyboe
Published: December 2008

Abstract. In order to assess whether a possible altered dopamine activity in normal-menstruating diabetic patients may influence the pituitary hormone secretion we have measured the basal serum concentrations of Prl, LH and FSH in 28 patients with insulin dependent diabetes mellitus (IDDM) and in 55 normal-menstruating women at day 3 to 6 of the menstrual cycle. In addition basal levels of oestradiol-17β, TSH, thyroxine (T4), triiodothyronine (T3) and resin-T3 uptake (RT3U) were determined in 17 patients with IDDM and in 17 controls. The responses of FSH, LH, Prl, GH and TSH to metoclopramide (MTC) administration (10 mg iv) were studied in 17 patients and 17 controls. In 10 patients with IDDM and 8 controls the short-term variations in pituitary hormones and blood glucose concentration were evaluated. Patients with IDDM had significantly lower basal levels of Prl (P < 0.01) and TSH (P < 0.05) and significantly (P < 0.05) higher basal levels of GH than normal women. No significant (P > 0.05) differences were found regarding basal serum concentrations of FSH, LH, oestradiol, T4, T3 and RT3U. During the 3 h period the mean coefficient of variation of Prl, FSH, LH and GH was not significantly (P > 0.05) different between diabetic patients and controls. Both groups responded significantly (P<0.01) in Prl and TSH to MTC but the TSH response was significantly (P < 0.05) lower in patients with IDDM. The Prl response to MTC was not significantly (P > 0.05) different within the two groups. None of the groups responded significantly (P > 0.05) in GH or gonadotrophins to MTC. No significant correlations (P > 0.05) were found between parameters of diabetes regulation and basal or stimulated hormone concentrations. Although, the interpretation of the results may be controversial it is suggested that the hormonal changes in normal-menstruating women with IDDM are to some extent compatible with a raised central dopaminergic activity.
Elevated serum calcitonin levels in patients with thyroid disorders
Authors: Oishi Seiichi , Shimada Tatsuya , Tajiri Junichi , Inoue Junnosuke , Sato Tatsuo
Published: December 2008

Abstract. Serum calcitonin was measured by radioimmunoassay (RIA) in 63 patients with hyperthyroidism, 37 with hypothyroidism, 9 with surgically proven medullary thyroid carcinoma (MTC) and 81 normal subjects. Provocative tests of calcitonin by calcium infusion were performed in 11 with hyperthyroidism, 10 with hypothyroidism, 6 with MTC and 14 normal subjects. Changes of calcitonin were also studied before and after treatment in 17 patients with hyperthyroidism and 12 with hypothyroidism. The basal calcitonin levels were increased in both hyperthyroidism (117 ± 60.1 pg/ml (mean ± sd): n = 63, P < 0.001) and hypothyroidism (137 ± 107 pg/ml, n = 37, P < 0.001), and significantly increased in MTC 14765 ± 25039 pg/ml, range 390 to 70400 pg/ml, n = 9, P < 0.001) compared with those in normal subjects (45.8 ± 22.3 pg/ml, n = 81). Increases of calcitonin during calcium load (iv 4.5 mg calcium/kg for 10 min) were significantly lower in both hyperthyroidism and hypothyroidism patients than in those in MTC. The calcitonin levels were not correlated with the serum T3, T4, TSH concentrations or titres of serum antithyroid antibodies in hyperthyroidism and hypothyroidism. We found some tendency toward decreasing calcitonin levels with the euthyroid state after treatment in both groups, but the changes were not significant. Although exact mechanisms of increased calcitonin in hyperthyroidism and hypothyroidism were not clear, our findings suggest that a 2- to 3-fold elevation of calcitonin levels in these patients did not indicate malignancy; MTC could be readily differentiated by a calcium infusion test.
Tonic effect of endogenous TSH on the in vitro thyroid cAMP response to TSH
Authors: Ikeda Hitoshi , Uchimura Hidemasa , Nagataki Shigenobu
Published: December 2008

Abstract. The present study was undertaken to compare the effects of 3,5,3'-triiodothyronine (T3) alone and T3 plus bovine thyrotrophin (bTSH) given chronically in vivo on the TSH-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) production in a mouse thyroid in vitro. Mice were given T3 (5 μg/ml) in drinking water for 4 days. The thyroid cAMP concentrations after an incubation with 10 mU/ml of TSH for 10 min were decreased by 50% in T3-treated mice as compared to the control. In the second experiment, mice were given T3 alone or T3 plus 0.5 mU of bTSH ip daily for 4 days. The combined treatment with T3 and TSH partially restored the reduction of cAMP response to TSH that was induced by T3 alone. In the third experiment, mice were given T3 alone for 7 days, or T3 for 7 days plus TSH for the last 3 days. The reduced cAMP response to TSH induced by T3 alone was again partially restored by the concomitant treatment with TSH.

These results indicate 1) that the capacity of the thyroid cAMP to respond to TSH is regulated, at least in part, by a trophic effect of endogenous TSH and 2) that the impaired capacity caused by a loss of tonic effect of endogenous TSH is reversible.
Thyroid hormone maintains normal circadian rhythm of blood corticosterone levels in the rat by restoring the release and synthesis of ACTH after thyroidectomy
Authors: Murakami Noboru , Hayafuji Chieko , Takahashi Kiyohisa
Published: December 2008

Abstract. The role of thyroid hormone in maintenance of the circadian adrenocortical rhythm was studied in the rat. The amplitude of the circadian rhythm of blood corticosterone levels gradually decreased with time after thyroidectomy, and by 5 weeks the rhythm disappeared. However, the circadian peak elevation constantly occurred just before the onset of the dark period until 4 weeks. Three weeks after thyroidectomy, daily overall treatment with thyroxine (T4) or 3,5,3'-triiodothyronine (T3) completely restored the amplitude of the circadian adrenocortical rhythm to the previous level within 2 weeks. Thyroidectomy did not affect the circadian rhythm in water intake.

However, thyroidectomy resulted in a loss of significant difference of plasma adrenocorticotrophin (ACTH) levels between the morning and the evening, by decreasing the evening levels. Similarly, pituitary ACTH content was decreased by thyroidectomy. Replacement of T4 completely restored the decreased ACTH levels to the previous ones.

These results suggest that thyroid hormone plays an important role in maintenance of the normal amplitude in circadian adrenocortical rhythm in the rat, by affecting ACTH synthesis.
Kinetics of steroid responsiveness to hCG during chronic inhibition of testicular function by GnRH analogue
Authors: Vicari Enzo , Mongioi Alessandro , Aliffi Antonia , Gulizia Salvatore , D'Agata Rosario
Published: December 2008

Abstract. The effect of daily injections of D-Ser-(TBU)6-LRH-EA10 (GnRH analogue (GnRH-A) 100 μg sc) on serum testosterone (T),17α-hydroxyprogesterone (17OHP) and oestradiol-17β (E2) was studied in 4 men. During GnRH-A therapy T, 17OHP and E2 were markedly decreased by the end of the second month. Continuous long-term administration of GnRh-A inhibited testicular function. To test whether the biosynthetic pathway was affected by the regimen, a bolus of 2000 U hCG was given to each subject after 10 months of therapy. Evaluation of the kinetics of steroid responsiveness showed a significant release of T in response to the trophic stimulus, with little or nor elevation of serum 17OHP and E2. The response seen in these treated men appeared similar to that found in hypogonadotrophic men and prepubertal boys.
Effect of somatostatin on growth hormone and prolactin response to dermorphin in man
Authors: Uberti E. C. degli , Trasforini G. , Salvadori S. , Margutti A. , Teodori V. , Rotola C. , Tomatis R. , Pansini R.
Published: December 2008

Abstract. The effects of iv somatostatin (somatotrophin release inhibiting factor (SRIF)) on growth hormone (GH) and prolactin (Prl) response to dermorphin (D) were tested in 6 healthy men. In all subjects D induced a significant increase in GH and Prl levels, as expected. SRIF completely blocked the GH-releasing activity of D, whereas it only reduced the Prl-releasing activity.

The results confirm that D is a potent stimulant for GH and Prl release in man, and furthermore demonstrate that the action of D on GH secretion can be completely overridden by SRIF.
Effects of small doses of bovine TSH on serum levels of free and total thyroid hormones, their degradation products, and diiodotyrosine
Authors: Benker G. , Splittstößer C. , Meinhold H. , Olbricht Th. , Reinwein D.
Published: December 2008

Abstract. Bovine TSH was administered iv to 10 normal volunteers in doses of 2.5, 7.5, 15 and 30 mU/kg. Brisk elevations of serum diiodotyrosine occurred already after the smallest dose (mean, + 183%) while larger doses had only slight additional effects. T3 rose much higher than T4 (+71% compared to +23% after 15 mU bTSH/kg), and free thyroid hormones exhibited changes similar to total T3 and total T4. The mean absolute increase in serum fT3 ranged from 2.03 to 9.04 pmol/l and proved to be an easily measurable parameter for the TSH effect. Dose-response effects were seen for the increases of fT4, fT3 and T3. TBG and rT3 did not change but the degradation product 3,3'-T2 showed large increments of serum levels. There was no correlation between the response of T3 and T4, fT3 and fT4, or diiodotyrosine and any of the other parameters of thyroid function. The interindividual differences in the magnitude of thyroid hormone response to TSH were considerable, and there was no relationship between this response and thyroid volume by ultrasound. We conclude that direct stimulation of the thyroid gland with bTSH in small doses leads to consistent increases of thyroid hormones, especially T3 and fT3, that the response varies between individuals, and that the precursor diiodotyrosine is released together with thyroid hormones.
The effects of parathyroid hormone on osteoblast-like cells from embryonic chick calvaria
Authors: Hall A. K. , Dickson I. R.
Published: December 2008

Abstract. A bone cell fraction was isolated from 16 day old embryonic chick calvaria using a sequential enzymatic digestion procedure. The fraction contained cells, of an osteoblast-like character, which responded to parathyroid hormone (PTH) and prostaglandin E2, but not to calcitonin, in terms of increased production of cyclic AMP. Primary cultures of cells maintained their responsiveness to PTH for at least 2 weeks after reaching confluence. Production of alkaline phosphatase by the bone cells was inhibited when 1,25(OH)2 vitamin D3 was added to cultures at concentrations of 10−8 m or greater. When cells were cultured in the presence of PTH a biphasic effect was observed; alkaline phosphatase levels were stimulated at low concentrations of this hormone but were decreased at higher concentrations. The latter finding appears consistent with observations that PTH can in vivo exert either anabolic or catabolic effects on bone, depending upon the circulating level of hormone present.
Effects of insulin on altered mineral and vitamin D metabolism in streptozotocin-induced diabetes
Authors: Ishida Hitoshi , Seino Yutaka , Nishi Shigeo , Kitano Norikazu , Seno Michiyo , Taminato Tomohiko , Matsukura Shigeru , Ishizuka Seiichi , Imura Hiroo
Published: December 2008

Abstract. In order to ascertain whether or not abnormal mineral and vitamin D metabolism in diabetes can be reversed by insulin therapy, plasma calcium, ionized calcium, phosphorus, parathyroid hormone (PTH) and vitamin D metabolites were measured in control, streptozotocin (STZ) diabetic and insulin-treated diabetic rats. Blood glucose levels in diabetic rats treated with insulin decreased to normal. The low plasma calcium and ionized calcium levels in diabetic rats were found to be normal in insulin-treated diabetic rats. An elevated PTH level was observed in the diabetic group, but it was at normal levels in the insulin-treated diabetic group. Plasma 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) in the diabetic group were decreased compared to those in control rats, but these were also fully restored to control levels by insulin therapy. However, plasma 1,25-dihydroxyvitamin D (1,25(OH)2D) levels in the untreated diabetic group tended to be lower than in controls, and the values in insulin-treated rats were significantly decreased compared to the control group. The ratio of 1,25(OH)2D to 25(OH)D in diabetic rats was higher than in controls, but it was decreased after insulin therapy and was significantly lower than in the control group. It is suggested, therefore, that the negative calcium balance and decreased 25(OH)D and 24,25(OH)2D levels are derived from the metabolic derangement due to the insulin deficiency. Furthermore, insulin seems to suppress the conversion of 25(OH)D to 1,25(OH)2D in experimental diabetes in vivo.
Concentration patterns of plasma dehydroepiandrosterone, Δ5-androstenediol and their sulphates, testosterone and cortisol in normal healthy women and in women with anorexia nervosa
Authors: Sirinathsinghji D. J. S. , Mills I. H.
Published: December 2008

Abstract. Plasma levels of cortisol, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), Δ5-androstenediol (Δ5-DIOL), Δ5-androstenediol sulphate (Δ5-DIOL-S) and testosterone were determined every 2 h from 10.00 to 22.00 h in 8 normal women and 10 with anorexia nervosa. Plasma levels of cortisol, DHA and Δ5-DIOL were significantly (P < 0.001) higher while DHAS levels were significantly (P < 0.001) lower in the anorexic women. The levels of Δ5-DIOL-S and testosterone were similar in both groups of women. In the normal women there were significant (P < 0.001) diurnal fluctuations in the levels of cortisol, DHA and DHAS with high levels in the morning and a nadir in the evening; however, there were significant P < 0.001) 'reverse' diurnal fluctuations in the levels of Δ5-DIOL, Δ5-DIOL-S and testosterone with low levels in the morning and elevated levels in the evening. In the anorexia nervosa women there was a loss of the diurnal variation in the levels of cortisol, DHA and DHAS and Δ5-DIOL-S; the diurnal variations of Δ5-DIOL and testosterone levels in the anorexic women were similar to those in the normal women. In general, these findings support the suggestion of a disturbance in the mechanisms regulating hypothalamic-pituitary-adrenal function resulting from a primary hypothalamic defect and/or abnormal alterations in steroid metabolism associated with the malnutrition in anorexia nervosa.
Effect of naloxone on oxytocin-induced cortisol decrease in normal men
Authors: Coiro V. , Chiodera P. , Rossi G. , Volpi R. , Salvi M. , Camellini L. , Roti E.
Published: December 2008

Abstract. iv administration of oxytocin decreases plasma ACTH-cortisol levels in normal men. In contrast, naloxone, a specific opioid antagonist, stimulates cortisol release, suggesting that opioid peptides exert an inhibitory control on ACTH-cortisol secretion.

The present study was carried out in an attempt to determine whether an opioid pathway mediates oxytocin action; therefore, we evaluated the effect of naloxone on the decrease of cortisol induced by oxytocin.

Six normal men were treated iv with oxytocin (2 IU as a bolus), naloxone (4 mg as a bolus plus 10 mg infused for 2 h) or a combination of the 2 drugs. Plasma cortisol levels were determined in samples taken before and 2 h after drug treatment. As expected, administration of oxytocin significantly decreased cortisol secretion, while naloxone had a stimulatory effect on plasma cortisol levels. When oxytocin injection was followed by administration of naloxone, cortisol levels remained unchanged; thus, naloxone abolished a cortisol decrement in response to oxytocin.

These findings show that in man oxytocin requires an active opioid system in order to produce its inhibitory action on ACTH-cortisol secretion, suggesting that this effect of oxytocin could be mediated by an opioid pathway.
Components of the rat conceptus that account for prolactin inhibition
Authors: Yogev L. , Terkel J.
Published: December 2008

Abstract. The secretions from developed concepti in the rat appear to inhibit both the rhythmic nocturnal secretion of prolactin (Prl) during the second half of pregnancy and the neurally mediated Prl release in response to suckling stimulation. In order to identify the parts of the concepti capable of inhibiting Prl secretion, the components of the concepti were systematically removed and their effect on plasma Prl levels was examined.

In the first experiment, female rats which were simultaneously pregnant and lactating were tested for Prl secretion in response to suckling stimulation after one of the following treatments: 1) removal of the foetuses only, 2) removal of the foetuses and trophoblasts, 3) removal of the complete concepti. In the second experiment, pregnant rats were tested for the presence of nocturnal Prl surges after either removal of the foetuses and trophoblasts or removal of the entire concepti.

The results indicate that after removal of the foetuses alone, the inhibition of Prl secretion remains. Following removal of both the foetus and the trophoblast, leaving the decidua in situ with a supplementary progesterone implant, the decidua still retain a partial capacity to inhibit Prl secretion in response to suckling stimulation, while their inhibitory effect on the nocturnal Prl surges was very minute. Degeneration of the decidua occurred following the removal of the trophoblast, when no exogenous progesterone was supplied. The deterioration of the decidua or total removal of the concepti eliminates the entire inhibition of Prl secretion, both on the nocturnal surges as well as in response to suckling stimulation.

Thus, it appears that after mid-pregnancy the trophoblast cell secretes a substance that both inhibits Prl secretion and maintains the corpus luteum, whereas the decidua at the same time secretes a substance that has a partial capacity to inhibit Prl secretion in response to suckling stimulation.
Forskolin stimulation of naphthylamidase in guinea pig thyroid sections detected with a cytochemical bioassay
Authors: Ealey Patricia A. , Kohn Leonard D. , Marshall Nicholas J. , Ekins Roger P.
Published: December 2008

Abstract. Forskolin, from the roots of the Indian medicinal plant Coleus forskohlii, has recently been shown to be a potent stimulator of adenylate cyclase in many systems, including endocrine tissues such as the thyroid gland. We describe forskolin activation of β-naphthylamidase activity in guinea pig thyroid tissue using the cytochemical bioassay (CBA) for thyroid stimulators. This CBA is the most sensitive bioassay for TSH and LATS-B currently available, being able to detect stimulation by doses as low as 10−5 mU TSH/l and 10−9 mU LATS-B/l. The dose-response curve to forskolin was bell-shaped (as is seen with TSH and LATS-B) with the ascending limb of the curve produced by 10−13 m to 10−12 m forskolin after a 3 min exposure time. Maximal stimulation was observed with 10−12m forskolin. However, the dose-response curve to forskolin was not parallel to that given by TSH, the slope of the ascending limb being much greater. It has been suggested that stimulation of β-naphthylamidase activity in the CBA is via cAMP. We report that dibutyryl cAMP at doses from 10−16m to 10−11 m produces a bell-shaped dose-response curve with a very broad peak response, again not parallel to that produced by TSH. Forskolin activation of β-naphthylamidase in the CBA is unaffected by a 1:106 dilution of 11E8, a monoclonal antibody raised against solubilised TSH receptors, which binds to the TSH receptor and inhibits TSH stimulation. Although the precise location of forskolin action is not known, this is further evidence that forskolin acts at a post-surface receptor site.
Evidence for metabolic regulation of pancreatic glucagon secretion by l-glutamine
Authors: Östenson Claes-Göran , Grebing Carin
Published: December 2008

Abstract. To investigate effects by i-glutamine on pancreatic A-cell secretion and intermediary metabolism, isolated pancreatic islets from normal and streptozotocin treated guinea pigs (A-cell rich islets) were incubated in the presence of glucose (5.5 mm) ± l-glutamine (10 mm). Glutamine significantly enhanced glucagon release from 297 ± 54 to 528 ± 53 pg/μg DNA/h in normal islets and from 553 ±31 to 806 ± 50 pg/μg DNA/h in A-cell rich islets. All results were expressed on the basis of islet DNA concentration, being 66 ± 4 ng DNA per normal islet and 32 ± 2 ng DNA per A-cell rich islet. Simultaneously, glutamine suppressed glucose oxidation to 64 per cent in normal islets and to 47 per cent of basal oxidation in A-cell rich islets. Islet content of ATP was also reduced by glutamine to about 60 per cent in A-cell rich islets, but not significantly changed in normal islets. Glutamine oxidation, at 5.5 mm-glucose, was considerably higher in A-cell rich islets (911 ±65 pmol/μg DNA/h) than in normal islets (313 ± 52 pmol/μg DNA/h). Addition of porcine insulin (25 mU/ml) counteracted these effects by glutamine, i.e. suppressed glucagon release but increased glucose oxidation and ATP content of the A-cell rich islets. The present findings demonstrate that glutamine stimulates glucagon release and is readily metabolized by the A-cells, Furthermore, the regulation of glucagon secretion by glutamine appears to be reciprocally related to factors affecting glucose metabolism and ATP-levels in the A-cell.
Epidermal growth factor in mouse urine: non-blood origin, and increase by sialoadenectomy and T4 therapy
Authors: Perheentupa J. , Lakshmanan J. , Fisher D. A.
Published: December 2008

Abstract. To study the origin and regulation of urinary epidermal growth factor (U-EGF), we measured EGF in adult female mouse plasma, urine and kidney tissue. We also studied the effects of excision of the submandibular salivary gland (SMG) and, after SMG excision and sham operation, 10-day therapies with T4 (0.4 μg/g daily), testosterone propionate (TP, 12.5 μg/g every 48 h), and SMG extract (25 μg EGF daily). We measured EGF with a specific liquid phase radioimmunoassay. The mean apparent urinary clearance was 150-fold higher for EGF than for urea. U-EGF was increased 24 h after the last sc injection of SMG extract. SMG excision caused a 2.2-fold increase in U-EGF and in apparent EGF clearance. T4 brought about a 1.5 to 1.75-fold increase in U-EGF while TP was without effect. Kidney EGF (K-EGF) responded to T4 and TP like U-EGF, but SMG excision and extract were without effect on K-EGF. We conclude that 1) the immunoassayable EGF in blood plasma and SMG-EGF do not appear to be major sources of U-EGF but plasma EGF may be a minor source, 2) kidney tissue appears not to be a major source of U-EGF, 3) production of U-EGF is activated by SMG excision, 4) T4 increases both U- and K-EGF while testosterone has no effect.
Effect of metoclopramide, domperidone and apomorphine on GH secretion in children and adolescents
Authors: Massara F. , Tangolo D. , Godano Adriana , Goffi Stefania , Bertagna Angela , Molinatti G. M.
Published: December 2008

Abstract. The way in which the dopaminergic system controls GH secretion in infancy and adolescence was investigated by studying the effects on GH of a specific dopaminergic agonist apomorphine, and two antagonists, metoclopramide (MC), which can and domperidone (DOM), which cannot cross the blood-brain-barrier, (BBB), in 14 males and 6 females aged 8–17 years. Treatment with both antagonists was followed by a marked increase in Prl, whereas only MC stimulated GH secretion, suggesting that this action must occur inside the BBB if it is linked to antidopaminergic properties. GH secretion was also stimulated by apomorphine, which acts at the central level. The paradox posed by the presence of a central effect on GH secretion derived from both an agonist and an antagonist of the dopaminergic receptors is discussed.
Prolactin secretion by mixed ACTH-prolactin pituitary adenoma cells in culture
Authors: Yamaji Tohru , Ishibashi Miyuki , Teramoto Akira , Fukushima Takanori
Published: December 2008

Abstract. To characterize the functional aspect of prolactin (Prl) cells coexisting with corticotroph adenomas, pituitary adenoma cells obtained from a patient with Cushing's disease and a patient with Nelson's syndrome, who were associated with hyperprolactinaemia, were cultured in monolayer and their Prl responses to various secretagogues were compared with those of prolactinoma cells in culture. Immunohistochemistry performed in one of these two adenomas demonstrated the presence of Prl-containing cells in addition to ACTH cells. When ACTH-Prl adenoma cells were exposed to ovine corticotrophin-releasing factor (CRF), a dose-dependent increase in both ACTH and Prl secretion was observed, which was blocked by coincubation with hydrocortisone. In contrast, no stimulatory effect of CRF on Prl release was observed in all of the experiments using prolactinoma cells. Thyrotrophin-releasing hormone, which consistently stimulated Prl secretion in ACTH-Prl adenomas, was effective in triggering Prl release in only 25% of the prolactinomas. Exposure of the cultured cells to lysine vasopressin, growth hormone-releasing factor and vasoactive intestinal peptide resulted in an increase in ACTH and Prl secretion in one ACTH-Prl adenoma, however, none of the prolactinomas responded to these stimuli to secrete Prl. Dopamine and somatostatin, on the other hand, uniformly suppressed Prl secretion from ACTH-Prl adenomas as well as from prolactinoma cells. These results suggest that the mode of Prl secretion by mixed ACTH-Prl pituitary adenomas is not identical to that by pure prolactinomas and is, at least in part, common to that of ACTH secretion.
Hyperthyroidism following primary hypothyroidism in association with polyendocrine autoimmunity
Authors: Bell P. M. , Sinnamon D. G. , Smyth P. P. A. , Drexhage H. A. , Haire M. , Bottazzo G. F. , Atkinson A. B.
Published: December 2008

Abstract. A 37 year old male with a strong family history of autoimmune disease presented with typical symptoms of hyperthyroidism. He had exophthalmos but no goitre. Hyperthyroidism was confirmed by failure of 131I neck uptake to suppress after 7 days treatment with triiodothyronine. Six years previously a diagnosis of primary hypothyroidism has been made. At diagnosis of hyperthyroidism, thyroglobulin antibodies, thyroidal microsomal antibodies and thyroid stimulating immunoglobulins were detected. The absence of thyroid growth stimulating immunoglobulins and presence of immunoglobulins blockink TSH-induced growth may account for the absence of goitre throughout. HLA -B8, -B, -DR3 and -DR4 genotypes, low C4 complement cocentrations and islet cell autoantibodies were detected at the time of diagnosis and 1 year later diabetes mellitus developed.
Nuclear reverse T3 binding sites: an artefact of isolation?
Authors: Hartong R. , Wiersinga W. M.
Published: December 2008

Abstract. Binding of [125I]rT3 to rat liver nuclear extracts prepared in 0.25 m sucrose could be abolished by a prior wash of the nuclei with 2.4 m sucrose. Analysis of mixtures containing [125I]rT3 and nuclear extracts (0.25 m sucrose) showed that after incubation for 2 h at 22°C, degradation of rT3 into 3,3'-T2 and I- had taken place. It appears that the presence of 125I- in these mixtures can account for the previously observed 'binding' of [125I]rT3 to these nuclear extracts.

Further characterization of the deiodination process in nuclear extracts showed: 1) inactivation by heating, 2) production of equimolar amounts of I- and 3,3'-T2, 3) stimulation by sulfhydryl compounds and inhibition by propylthiouracil in a fashion similar to the microsomal iodothyronine 5'-deiodinase (ping-pong mechanism).

We conclude that the observed deiodination of rT3 in hepatic nuclear extracts is of enzymatic nature, due to contamination of the nuclear preparation by microsomal iodothyronine 5'-deiodinase. However, since the nuclei are prepared in the presence of the non-ionic detergent Triton X-100, a nucleus associated deiodinase activity cannot be totally excluded.
Testicular response to human chorionic gonadotrophin in chronic hyperprolactinaemia
Authors: Heshmati H. M. , Turpin G. , Nahoul K. , Carayon A. , Salmon D. , Gueguen A. , de Gennes J. L.
Published: December 2008

Abstract. In order to evaluate the effect of hyperprolactinaemia on gonadal function in men, testicular stimulation by human chorionic gonadotrophin (hCG) (5000 IU/day, 3 consecutive days) was performed on 6 men with chronic hyperprolactinaemia and 6 control subjects. The following parameters were measured before and during the 4 consecutive days following the injections of hCG: the concentration in plasma of testosterone (T), oestradiol-17β (E2), dihydrotestosterone (DHT) and the urinary excretion of testosterone glucuronide (TG) and 5α-androstane-3α,17β-diol glucuronide (3α-DiolG). The rises in T, E2, DHT and the ratios of T/DHT and TG/3α-Diol G were similar in both groups, but the rises in TG and 3α-Diol G were lower in the hyperprolactinaemic group after hCG. There was no correlation between the response of T and the increment of E2 in either group. It is suggested that in men with chronic hyperprolactinaemia: 1) there is diminished testicular response to hCG; this could be due to chronic gonadotrophin deficiency or to a direct effect of hyperprolactinaemia on the testes, 2) there is no modulation of T synthesis through inhibition of aromatase activity and E2 secretion and 3) the 5α-reduction of T is not deficient.
The effect of nifedipine on CRF-41 and AVP-induced ACTH release in vitro
Authors: Murakami Kazuharu , Hashimoto Kozo , Ota Zensuke
Published: December 2008

Abstract. The effect of nifedipine on CRF-41- and AVP-induced ACTH release was examined using monolayer cultured rat anterior pituitary cells and pituitary halves. Nifedipine inhibited ACTH release induced by synthetic rat CRF-41 in two systems. In pituitary halves, CRF-41 significantly stimulated both ACTH release and cyclic AMP accumulation. Nifedipine inhibited CRF-41-induced ACTH release and the inhibitory effect of nifedipine on CRF-41-induced ACTH release was accompanied by parallel decrease of cyclic AMP levels in pituitary halves. Nifedipine did not inhibit AVP-induced ACTH release in pituitary halves, and AVP did not significantly affect cyclic AMP accumulation in pituitary halves. These results suggest that CRF-41 stimulates ACTH release through the intracellular cyclic AMP system and calcium-calmodulin system which are accelerated by the influx of extracellular calcium ions. Moreover, it is suggested that the calcium required for AVP-induced ACTH release is derived primarily from intracellular rather than extracellular sources.
Oestradiol binding to nuclei of anterior pituitary cells of the ram
Authors: Thieulant Marie-Lise , Pelletier Jean
Published: December 2008

Abstract. The methodology to fully characterise nuclear receptor for oestradiol-17β (E2) in the ram pituitary has been investigated. Purified nuclei, clean under the electron microscope, were obtained from 2.4 m sucrose ultracentrifugation and were extracted for 2 h at 0°C with 0.6 m NaCl. After centrifugation, the supernatant was incubated with [3H]E2 with or without a 100-fold excess of unlabelled E2.

The main results were:

the specific binding was maximum at 20°C in 2–3 h and remained constant up to 19 h without significant metabolism; an incubation temperature of 25°C reduces the binding, while at 0°C maximum binding was attained at a much slower rate;

the binding was linearly related to the dose of nuclear proteins;

the binding was not affected by DNase and RNase but was suppressed by trypsin, pronase or a temperature of 56°C;

binding was specific for oestrogens;

preincubation of cytosol with [3H]E2 and then coincubation with nuclei showed an uptake of the [3H]E2 receptor complex by nuclei; such a transfer was inhibited if cytosol was previously heated;

after a prelabelled cytosol-nuclei coincubation, a specific binding peak was found in the nuclear extract submitted to sucrose gradient sedimentation (4.1S);

in vivo injection of 100 μg E2 resulted in a sharp increase in nuclear receptor numbers 30 and 60 min later, with a concomitant drop in cytosolic receptor numbers.

These results indicate that E2 can bind to pituitary nuclei in the ram.
Studies on the glucocorticoid-receptor blocking action of RU 38486 in cultured ACTH-secreting human pituitary tumour cells and normal rat pituitary cells
Authors: Lamberts S. W. J. , Bons E. G. , Uitterlinden P.
Published: December 2008

Abstract. The glucocorticoid-receptor blocking actions of RU 38486, a new compound with anti-progesterone activity, have been investigated in cultured human ACTH-secreting pituitary tumour cells and normal rat pituitary cells.

Pre-incubation of human pituitary tumour cells for 24 h with RU 38486 (1 μm) did not influence basal or CRF-stimulated ACTH release. RU 38486 (100 nm–1 μm) significantly overcame or prevented the dexamethasone (100 nm–1 μm)-induced inhibition of CRF-stimulated ACTH release by the cultured tumour cells prepared from 2 patients with Cushing's disease. The tumour cells of a third patient were insensitive to CRF. Pre-incubation for 24 h with 1 μm RU 38486 facilitated CRF-stimulated ACTH release significantly.

Studies with cultured normal rat pituitary cells showed that the inhibiting effect of 24 h pre-incubation with 10 and 50 nm dexamethasone on CRF-stimulated ACTH release could be acutely (measured over 4 h) overruled in a dose-dependent way by RU 38486 (100 nm, 1 and 10 μ), while pre-incubation for 24 h of these cells with RU 38486 (100 nm and 1 μm) significantly attenuated the acute inhibiting effect of 1 μm dexamethasone on CRF-stimulated ACTH-release.

The results of these in vitro experiments are discussed against the background of the possible therapeutic use RU 38486 in patients with Cushing's syndrome in order to block the deleterious effects of high circulating cortisol concentrations.
Protein turnover in different types of skeletal muscle during experimental hyperthyroidism in rats
Authors: Angerås Ulf , Hasseigren Per-Olof
Published: December 2008

Abstract. Exeprimental hyperthyroidism was induced in rats by daily ip injection of triiodothyronine (T3; 100 μg/100 g body weight) during 3 or 10 days. Protein synthesis and degradation were measured in incubated soleus and extensor digitorum longus (EDL) muscles by determining rate of tyrosine incorporation into protein and release of tyrosine to the incubation medium respectively. Protein synthesis was unaffected by T3 administration during 3 or 10 days. Protein breakdown was significantly increased in soleus but unchanged in EDL in the 3-days experiment. Following administration of T3 for 10 days proteolysis was increased in both muslces. Weight of the soleus muscle was reduced after T3 for 3 days. After 10 days weight and protein content were reduced in both muscles. The study demonstrated that reduced muscle protein content following administration of T3 was the result of increased proteolysis, not decreased protein synthesis. The results further indicate that slow muscle (soleus) is more sensitive to the effects of thyroid hormone than fast muscle (EDL).
Plasma growth hormone and thyroxine levels in the chronically catheterised pig foetus and the effect of thyrotrophin releasing hormone
Authors: Macdonald A. A. , Spencer G. S. G. , Hallett K. G.
Published: December 2008

Abstract. The circulating levels of growth hormone and thyroxine during the last 2 weeks of gestation, and the effect of thyrotrophin releasing hormone on their secretion, has been examined in 13 chronically catheterised pig foetuses. Porcine growth hormone, measured by homologous radioimmunoassay, in the foetal plasma was found to average 83.5 ± 10.3 ng/ml, while thyroxine levels were 92.9 ±4.1 nmol/l. There was no change in thyroxine or growth hormone levels with gestational age. Injection of 5 μg TRH produced a marked increase in plasma growth hormone levels (+ 194 ± 51 ng/ml) but no change in thyroxine was observed. Injection of saline and subsequent blood sampling had no effect on the levels of either growth hormone or thyroxine.
Median charge and charge heterogeneity of human pituitary FSH, LH and TSH
Authors: Wide Leif
Published: December 2008

Abstract. The charge and charge heterogeneity of FSH, LH and TSH in 63 extracts of individual human pituitaries were investigated by use of zone electrophoresis in 0.17% agarose suspension in veronal buffer at pH 8.6 followed by hormone analyses by radioimmunoassay. The migration velocities are similar to those in free solution and directly proportional to differences in charge in the buffer. The technique gave highly reproducible results and the recovery of hormone activity after electrophoresis was about 100%. Methods for estimation of median charge, expressed as median migration rate, and of degree of charge heterogeneity are described. Each pituitary contained a sequence of different forms, estimated at 20 or more, of each of the three hormones, with minor differences in charge. The degree of charge heterogeneity within the pituitary was similar for FSH, LH and TSH. The distribution curves of radioimmunological activity in relation to migration rate were close to normality for the three glycoprotein hormones. This was in contrast to that found for Prl and GH. The merits of the electrophoretic technique are discussed.
Median charge and charge heterogeneity of human pituitary FSH, LH and TSH
Authors: Wide Leif
Published: December 2008

Abstract. The median charge and the degree of charge heterogeneity of FSH, LH and TSH in extracts from pituitaries of 63 individuals were determined by electrophoresis in 0.17% agarose suspension at pH 8.6 followed by hormone analyses by radioimmunoassay. Charge was expressed as migration rate in relation to that of human serum albumin. FSH, LH and TSH showed similar degrees of charge heterogeneity within the pituitary, and this degree of heterogeneity was not related to sex or age. There was a sex- and age-related variation in median charge of FSH and LH but not of TSH. The forms of FSH and LH were more acidic at higher ages and the most acidic forms were found in elderly women. Women 32 to 47 years old had more acidic forms of FSH than those 14 to 20 years of age. The median charge of LH was similar in young men and women, while that of FSH was more basic in young women than in young men. These results indicate that the effect of gonadal feedback on the molecular charge is different for FSH and LH. Studies with neuraminidase-treated pituitary extracts indicated that the sex- and age-dependent variations of the charge on FSH were due to differences in the sialic acid content. The amount of FSH in the pituitary was significantly smaller in men than in women. The contents of TSH and LH in the pituitary were lower in the higher age groups. No such decrease with age was found for FSH.
Sex-dependent endorphinergic and adrenergic control mechanisms of luteinizing hormone secretion in immature rats
Authors: Schulz Rüdiger , Wilhelm Annemarie , Pirke Karl Martin , Herz Albert
Published: December 2008

Abstract. Previous studies in male and female immature rats have revealed striking sex differences as concerns endorphinergic and adrenergic control of luteinizing hormone (LH) secretion. The present study examines in 10 days old male and females rats whether these differences result from sexual differentiation of the brain, or acute effects of male and female gonadal hormones. The techniques employed to manipulate these mechanisms were gonadectomy immediately post-partum and androgenization. Androgenization on the 1st and 2nd day of life reduces the ability of naloxone to elevate serum LH levels in females, but failed to modify the LH-elevating effect of clonidine in males. Experiments with castrates showed that testosterone is critical for these sex-related differences. Treatment with testosterone on the 9th day of life of intact or gonadectomized rats revealed the ability of this hormone to modify LH-release acutely. We conclude that sexual differentiation of the brain may be of minor significance for the sex-related LH-control mechanisms in prepubertal rats. Of importance is the acute presence of testosterone, since in its absence male characteristics disappear.
Prolactin inhibits oestradiol-induced luteinizing hormone release at the pituitary level
Authors: Miyake Akira , Terakawa Naoki , Tasaka Keiichi , Shimizu Ikuya , Ohtsuka Shirou , Lee Jin-Woo , Aono Toshihiro
Published: December 2008

Abstract. The direct action of prolactin (Prl) on pituitary LH secretion was studied by examining its effect on oestradiol (E2)-induced luteinizing hormone (LH) release from the rat pituitary in a perifusion system and determining the oestrogen receptor (ER) content of the pituitary in hyperprolactinaemic female rats. When the pituitary from rats in pro-oestrus was perifused with medium alone, 10−7 m E2 significantly (P < 0.05) increased the LH concentration in the effluent by 60–130% of the basal level, but in medium containing 1 μg/ml Prl it did not cause LH release. In hyperprolactinaemic rats produced by implanting 2 anterior pituitary glands under the kidney capsule, the ER content of the cytosol of the pituitary (53.2 ± 2.9 fmol/pituitary) was significantly increased (P < 0.05), but that of the nuclei (6.8 ± 0.2 fmol/pituitary) was significantly decreased (P < 0.05) compared with the contents in rats in pro-oestrus.

These data suggest that Prl has a direct suppressive effect on LH secretion from the pituitary in the rat, and that decreased translocation of ER into the nucleus might relate to impaired LH release by E2 from the pituitary of hyperprolactinaemic rats.
Effects of oestradiol benzoate on the pituitary secretion and peripheral kinetics of thyrotrophin in the rat
Authors: Boado Rubén , Deza Susana , Zaninovich Angel A.
Published: December 2008

Abstract. Previous works from this laboratory have demonstrated that oestradiol benzoate (EB) in euthyroid male and female rats induced a significant decrease in the pituitary content of TSH while serum levels of this hormone remained normal. The present work studied the effects of EB (25 μg/100 g body weight, during 9 days) on the peripheral metabolism of [125I]rTSH and on the pituitary and plasma concentration of TSH in euthyroid and hypothyroid rats. No significant variations were observed in [125I]rTSH kinetics of EB-treated euthyroid rats vs untreated controls: fractional turnover rate 2.8 ± 0.2 vs 3.0 ± 0.3%/min, distribution space 6.5 ± 0.4 vs 6.8 ± 0.5 ml/100 g body weight, disposal rate 18.4 ± 2.4 vs 18.1 ± 1.9 μU/100 g/min and extrapituitary pool 645 ± 42 vs 614 ± 43 μU/100 g body weight. Similarly, in hypothyroid rats oestrogens induced no changes in TSH kinetics except for an increase in distribution space (P < 0.025). However, oestrogens decreased the pituitary pool of TSH (P < 0.001) in both euthyroid and hypothyroid rats and increased the plasma TSH in hypothyroid animals (P<0.01), all vs their respective controls. Neither hypothyroid group had detectable plasma levels of T4 and T3. In summary: 1) the marked decrease of pituitary TSH with normal plasma TSH induced by EB appears unrelated to the peripheral metabolism of TSH, 2) the results from hypothyroid rats suggest that EB stimulates the release of TSH from the pituitary gland.
Effects of luteinizing hormone-releasing hormone (LRH) upon bioactive and immunoreactive serum LH in patients with Turner's syndrome before and after oestrogen treatment
Authors: Celani Marco Francesco , Montanini Vanna , Marrama Paolo
Published: December 2008

Abstract. One daily dose of 0.05 mg ethinyl oestradiol was administered to 5 patients with Turner's syndrome (mean age ± sem = 16.4 ± 0.7 years) for 10 days. The effects of acute stimulation with luteinizing hormonereleasing hormone (LRH) (0.1 mg iv) on biologically active and immunoreactive LH were analysed before therapy and at the end of oestrogen treatment. Bioactive LH (BIO-LH) was measured by a sensitive and specific in vitro bioassay based upon testosterone production by mechanically dispersed mouse Leydig cell preparations. Immunoreactive LH (RIA-LH) was evaluated by a double antibody RIA method. Prior to oestrogen treatment, LRH induced a prompt rise in BIO-LH and RIA-LH levels, which reached peak values at 30 and 45 min, respectively. After oestrogen treatment, a delayed response (with peak values at 120 min) was observed for both BIO-LH and RIA-LH. Before oestrogen treatment, the mean bioactivity to immunoreactivity (B/I) ratio of LRH-stimulated LH showed a significant decrease from basal values (P < 0.05). In contrast, after ethinyl oestradiol administration the mean LH B/I ratio increased significantly from basal values in response to LRH (P < 0.05). The mean relative maximum response (Δ%) for BIO-LH was significantly higher (P < 0.05) in oestrogen-treated than in untreated patients, whereas the mean BIO-LH Δ area was significantly lower in the former group (P < 0.01). Similarly, oestrogens decreased significantly the mean RIA-LH Δ area (P < 0.05), whereas they did not affect significantly the mean RIA-LH Δ%. The results further emphasize that oestrogens may change the quality of circulating LH.