bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased prolactin responsiveness to thyrotrophin-releasing hormone and metoclopramide in hyperthyroidism
Authors: Röjdmark Sven , Carlsson Anders
Published: December 2008

Abstract. To investigate whether prolactin (Prl) responsiveness to thyrotrophin-releasing hormone (TRH) differs in thyrotoxic and normal individuals, serum Prl was determined before and after iv injection of 200 μg TRH in 10 patients with untreated thyrotoxicosis and also in 9 normal subjects. Both the maximal Prl increment after TRH and the total Prl response, represented by the Prl incremental area, were significantly larger in the normal subjects compared with the thyrotoxic (max Prl increment 56 ± 11 vs 15 ± 3 ng/ml, P< 0.001; Prl incremental area 3071 ± 522 vs 579 ± 171, P <0.001; mean ± sem). The maximal Prl increase after 15 mg oral metoclopramide (MET) was also significantly larger in the normal (125 ± 13 ng/ml) than in the thyrotoxic subjects (60 ± 13 ng/ml, P < 0.01). When 200 μg TRH was injected iv 90 min after oral administration of 15 mg MET, an additional Prl increase was observed in normal individuals (21 ±6 ng/ml, P < 0.01). In thyrotoxic patients, however, iv TRH failed to induce a significant increase in Prl after oral priming with MET (0 ± 3 ng/ml). When 7 thyrotoxic patients, made euthyroid by 125I-treatment, were investigated according to the same protocol as the one mentioned above, they displayed normal Prl responses to iv TRH and to oral MET. Furthermore, they showed a significant Prl response to iv TRH after oral priming with MET (20 ± 8 ng/ml, P < 0.05). These findings imply that pituitary lactotrophs of untreated thyrotoxic patients might have cytoplasmic membranes with decreased permeability to Prl and/or reduced stores of releasable Prl which return to normal after oral 125I-therapy.
Somatomedin synthesis by a subclone of Buffalo rat liver cells. Influence of divalent cations on rIGF-II release
Authors: Mayer Peter W. , Schalch Don S.
Published: December 2008

Abstract. Previous studies have provided evidence that biosynthesis and secretion of somatomedin (SM) is not only hormone dependent, but also modulated by nutritional factors. Little is known, however, about the role of divalent cations in these processes. A subclone of Buffalo rat liver (BRL) cells, known to secrete rat insulin-like growth factor-II (rIGF-II) into serum-free medium, was used to define the influence of Ca2+, Mg2+ and Zn2+ on this function.

The secretion of rIGF-II by subclone BRL-3SC appears to be quite stable in minimal essential medium (MEM) over a wide range in Ca2+ concentrations (0.18–3.0 mm) but is reduced to only 8% of controls in the absence of Ca2+ (P <0.01). Reducing, and even eliminating, the extracellular concentration of Mg2+ alone caused no change in basal rIGF-II release, while simultaneously decreasing Mg2+ and Ca2+ results in a marked drop in the secretion of this SM, reaching a nadir of 38% of controls in the absence of Mg2+ (P <0.001). A Mg2+ concentration of 10 mm, or 25 times 'normal', did not alter the basal secretion of rIGF-II. Eliminating the trace amount (0.8 nm) of Zn2+ in MEM by chelation with EDTA decreased rIGF-II secretion to 62% of control levels (P<0.01), while increasing the concentration of this cation to 3 mm did not alter the basal release of this SM. Decreased rIGF-II release in the presence of EGTA and EDTA is not due to irreversible cell damage since the secretion of this SM was restored to normal during subsequent reincubation in MEM alone.

These studies indicate that normal rIGF-II secretion by BRL-3SC cells occurs only at concentrations of Ca2+, Mg2+ (in the presence of reduced Ca2+) and Zn2+ above certain threshold levels. Moreover, reduced Mg2+ alone, without a concomitant reduction in Ca2+, does not decrease rIGF-II release, attesting to the known interaction of these cations in a variety of intracellular processes. Concentrations of these three cations considerably higher than 'normal' appear to have no significant effect on basal rIGF-II secretion.
Participation of Ca2+ channel in liver calcium regulation by calcitonin in rats
Authors: Yamaguchi Masayoshi , Yoshida Hiroyuki
Published: December 2008

Abstract. A possible regulatory role of calcitonin (CT) upon liver calcium content was investigated by using a Ca2+ channel blocker in thyroparathyroidectomized (TPTX) rats. In bile duct-ligated TPTX rats, liver calcium content was not significantly increased by a single ip injection of calcium chloride (4.0 mg Ca2+/100 g body weight). Administration of CT (80 MRC mU/100 g) caused a remarkable elevation of liver calcium content. This hormonal effect was inhibited by administration of verapamil (1.0 mg/100 g) or lanthanum chloride (0.4 mg/100 g), Ca2+ channel blockers. CT administration markedly increased the transport of calcium into the bile through the liver cells of TPTX rats injected ip with calcium. This increase in the bile calcium content was prevented by administration of verapamil or lanthanum chloride. Administration of epinephrine (10 μg/100 g), vasopressin (10 μg/100 g), or concanavalin A (1.0 mg/100 g) produced a significant elevation of bile calcium content; these elevations were not significantly altered by addition of verapamil (1.0 mg/100 g). These data suggest the presence of CT receptors on liver cell plasma membranes which are involved in regulation of membrane Ca2+ channels. It is proposed that CT facilitates the entry of extracellular calcium into liver cells by opening Ca2+ channels located on their plasma membranes.
Modulation of prolactin mediated progesterone secretion by gonadotrophin subunits
Authors: Alexander J. Steven , Crisp Thomas M.
Published: December 2008

Abstract. The effects of preincubating rat granulosa cells with porcine LH, and its dissociated α and β subunits on subsequent Prl mediated progesterone secretion were examined. Granulosa cells were isolated from ovarian follicles 50 h after injection of 5 IU PMSG and were then cultured as monolayers in serum supplemented medium. Cells were preincubated for 24 h with medium alone (control) or with 0.1 or 1 μg/ml of LH, LHα, LHβ, or both LHα and LHβ. Cells were also preincubated with 50 ng/ml LHα and 50 ng/ml LHα that had been further purified with immunoaffinity chromatography. Following the preincubation period, cells were maintained an additional 6 days in the presence or absence of 1 μg/ml Prl. Preincubation with LH or its individual subunits markedly increased the responsiveness to Prl stimulation through 6 days of culture, whereas cells cultured in the absence of Prl secreted decreasing amounts of progesterone. Preincubation with the dissociated subunits increased Prl mediated progesterone secretion approximately two-thirds as much as preincubation with intact pLH. Immunopurified pLHα increased the responsiveness to Prl to the same degree as non-purified pLHα, suggesting that the stimulatory effects of the subunits are not due to contamination by intact LH. The magnitude of Prl mediated progesterone secretion was dependent upon the preincubation concentration of LH or its dissociated subunits in most, but not all treatments. The increased responsiveness to Prl suggests that in the proper endocrine environment, individual subunits of gonadotrophins may functionally interact with target cells.
Effects of oxytocin and vasopressin on the ovarian blood flow, progesterone and oestradiol-17β secretion in oestrous rats
Authors: Varga Bertalan , Horváth Edit , Zsolnai Béla
Published: December 2008

Abstract. Oestrous rats were anaesthetized with pentobarbital, one of the femoral arteries and veins and one of the ovarian veins were cannulated, and a thin polyethylene cannula was fixed in the ovarian bursa. Five-min blood fractions were collected from the ovary for 50 min. Following the control fractions 15 mU of oxytocin, 15 mU of vasopressin or 50 μl of 0.9% NaCl solution was given into the ovarian bursa over 10 min. Blood pressure and ovarian blood flow were continuously recorded. Progesterone (P) and oestradiol-17β (E2) were determined from the blood samples by RIA. Oxytocin did not alter the blood pressure, whereas the ovarian blood flow showed a short increasing tendency. Later, however, it started to decrease in parallel with the decrease in blood pressure owing to blood loss. The secretion of P and E2 remained unchanged. No changes in blood pressure were observed after vasopressin administration, although the ovarian blood flow quickly decreased in parallel with the secretion of P and E2.

It is suggested that oxytocin has no direct effect on ovarian blood flow and hormone secretion in the rat. Vasopressin, however, is an effective vasoconstrictor in the rat ovary and may in this way reduce hormone synthesis.
Thymus peptides interacting with opiate receptors
Authors: Zozulya Andrey A. , Pschenichkin Sergey Ph. , Shchurin Mikhail R. , Khomjakov Jury N. , Besvershenko Ivan A.
Published: December 2008

Abstract. The substances displacing labelled ligands from opiate receptors of the rat brain membrane fraction were found in the thymosin fraction 3 and acetoacid extract of the thymus by the radioreceptor assay. Comparison of the displacing activity of acetoacid extracts of perfused and non-perfused thymus and peripheral blood as well as an estimation of the blood content in the thymus allowed to conclude that blood does not participate in the ability of thymus preparations to bind to opiate receptors. On the basis of the enzymatic treatment data one can conclude that opiate receptor ligands present in thymus preparations are of peptide nature. The value of their sodium shift suggests that those peptides are partial agonists of morphine. The possible role of opioid peptides in the thymic endocrine function is discussed.
Dissociation between kallikrein and aldosterone in Cushing's disease with periodic hormonogenesis
Authors: Overlack Axel , Higuchi Miyoko , Kolloch Rainer , Müller Hans-Michael , Stumpe Klaus O. , Schweikert Hans-Udo
Published: December 2008

Abstract. It has been suggested that the renal kallikreinkinin system is dependent on mineralocorticoid activity. This hypothesis was studied in a patient with cyclic Cushing's syndrome combined with cortisol suppressible, dexamethasone non-suppressible ACTH secretion. The 24-h urinary excretions of sodium, potassium, cortisol, active and inactive kallikrein, aldosterone, and prostaglandin E2 (PGE2) were studied during normal and excessive cortisol secretion and after bilateral adrenalectomy. Kallikrein, PGE2 and potassium rose during cortisol overproduction while aldosterone and sodium decreased. Kallikrein, PGE and potassium were positively related to cortisol excretion, whereas urinary aldosterone and sodium showed a negative relationship to cortisol. Kallikrein was inversely related to aldosterone. Excretion of inactive kallikrein followed closely the changes of active kallikrein. During cortisol excess, as in our patient, the mineralocorticoid activity of cortisol will exceed that of aldosterone. This suggests that the alterations in kallikrein, aldosterone and PGE2 during cortisol excess in the present study were due to the mineralocorticoid potency of the steroid.
Changes in computed tomographic findings in microprolactinomas before and after bromocriptine
Authors: Demura R. , Kubo O. , Demura H. , Shizume K. , Kitamura K.
Published: December 2008

Abstract. Computed tomography (CT) of the pituitary before and after bromocriptine treatment were performed in 10 patients with microprolactinoma. Intra-pituitary low densities were demonstrated in 7 out of the 10 patients before bromocriptine. Low densities shrank in size and increased in density after normalization of the plasma prolactin (Prl) level following bromocriptine. At the same time, various degrees of empty sella were demonstrated in these patients and in 2 out of the 3 without noticeable changes before treatment. It was concluded that enhanced CT scans, especially sagittal reconstruction images, were very informative for the diagnosis of microprolactinoma and that bromocriptine reduced the size of the microprolactinoma and often led to empty sella.
Alterations of adrenergic systems in thyroid slices from patients with Graves' disease
Authors: Yamashita Kamejiro , Aiyoshi Yuji , Kuzuya Nobuaki , Koide Yoshinobu
Published: December 2008

Abstract. The responses to TSH of tissue cAMP levels in thyroid slices from patients with Graves' disease were significantly lower than those in normal thyroid slices. Conversely, tissue cAMP levels in thyroid slices from these patients were greatly increased by β-adrenergic agonists, either isoproterenol or norepinephrine compared with those in normal thyroid slices.

The elevation of cAMP levels induced by TSH in normal thyroid slices was significantly reduced by norepinephrine via α-adrenergic action as reported previously in canine thyroid slices, while such an elevation by TSH of cAMP levels in slices of Graves' disease thyroids was not inhibited, or rather increased by norepinephrine.

These results indicate that, in addition to low responses to TSH, α- and β-adrenergic systems were functionally altered in thyroid tissues of patients with Graves' disease.
Inhibitory action of somatostatin on meiotic maturation of cultured porcine follicular ova
Authors: Mori Takahide , Irahara Minoru , Saito Haruhiko , Ohno Yoshio , Hosoi Eiji
Published: December 2008

Abstract. To investigate the physiological importance of somatotrophin release-inhibiting factor (SRIF), effects in vitro of synthetic SRIF 14 on germinal vesicle breakdown (GVB) of cultured porcine follicular ova were studied. The proportion of ova with GVB decreased gradually and significantly with increasing concentrations of SRIF 14 in the range from 6 × 10−12 to 6 × 10−7 m during a 22 h period of culture. The inhibitory effect was apparent for the period between 14 and 22 h in the course of culture but was reversed by a concomitant addition of anti-SRIF to the medium. Neither synthetic oxytocin, vasoactive intestinal polypeptide nor substance P exerted any inhibitory or stimulatory action on GVB. These results suggest a limited but definite inhibitory action of SRIF on GVB of porcine ova.
Gel chromatography of immunoextracted plasma calcitonin in response to the calcium clamp in healthy males
Authors: Bucht Elisabet , Tørring Ove , Sjöberg Hans Erik
Published: December 2008

Abstract. A radioimmunoassay (RIA) was developed for immunoreactive calcitonin (iCT) in human plasma. Antibodies against synthetic human calcitonin (hCT) coupled to bovine serum albumin (BSA) were raised in rabbits and were directed against the carboxy terminal part of CT. The detection limit of the assay was 8 pg/ml. In 7 males the iCT response to a calcium-clamp was studied. Blood was collected at 0, 30 and 60 min after the start of the calcium infusion. iCT was measured directly in plasma and in extracts obtained after purification of plasma iCT by means of immobilized CT antibodies. There was a good correlation between iCT in plasma samples and extracts, r = 0.993, n = 14 (P < 0.001). Dilution curves of extracts and plasma were parallel with the hCT standard curves. Gel chromatography of the extracts on Sephadex G-50 and G-75 disclosed heterogeneity of iCT in normal plasma during basal conditions as well as during calcium stimulation. Thirty min after the start of the calcium clamp all molecular forms, most likely constituting monomeric and dimeric CT and larger forms, were increased, while after 60 min iCT seemed to constitute predominantly forms larger than monomeric CT. Basal levels of unextracted iCT in healthy males (n = 44, 37 ± 10 years) were 15 ± 9 pg-equivalents/ml (mean ± sd) which was higher than in females (n = 40, 32 ± 9 years) 11 ± 4 pg-equivalents/ml (P < 0.05).
Effect of angiotensin II on plasma ACTH in patients with Addison's disease
Authors: Haller Hermann , Bähr Volker , Exner Petra , Oelkers Wolfgang
Published: December 2008

Abstract. Short-term angiotensin II (All) infusions (3 ng/kg/min) were performed in 5 patients with Addison's disease in order to assess the effect of AII on ACTH secretion. Base line ACTH levels were elevated due to a 9-h time lag between hydrocortisone administration and onset of the study. In 2 separate infusion periods of 30-min duration, All had no unidirectional effect on plasma ACTH. Mean ACTH increased slightly but insignificantly. Mean blood pressure rose by about 10 mmHg. The degree of angiotensinaemia induced is probably similar to the state of moderate to severe sodium deficiency. Short-term changes of All in this order of magnitude have obviously no major effect on ACTH secretion.
Hyperlipidaemia in patients with hypopituitarism
Authors: Ishibashi Shun , Murase Toshio , Yamada Nobuhiro , Tanaka Kunimi , Takaku Fumimaro , Sato Kanji
Published: December 2008

Abstract. Five patients with hypopituitarism due to Sheehan's syndrome showed hyperlipidaemia of various lipoprotein phenotypes. Postheparin plasma lipoprotein lipase activity was subnormal in 4 of the 5 patients and hepatic triglyceride lipase was markedly decreased in all patients studied. After supplementation of both corticosteroid and thyroid hormones, lipoprotein lipase activity was restored to normal within 2 months, while it took longer for hepatic triglyceride lipase to return to normal. Together with the normalization of the two lipase activities, hyperlipidaemia subsided. The findings suggest that reduced activities of the two lipases may, at least in part, account for the development of hyperlipidaemia in hypopituitarism. The study identifies a new group of patients with hyperlipidaemia secondary to a disorder in endocrine function.
The effect of 6-hydroxydopamine infused into the third cerebral ventricle on the plasma cortisol concentration in sheep subjected to repeated and prolonged stress stimuli
Authors: Domański E. , Stupnicka E. , Przekop F. , Wolińska-Witort E.
Published: December 2008

Abstract. It has previously been observed that sheep subjected to repeated and prolonged stress stimuli showed biphasic cortisol responses. On the first and second day of stimulation an elevation was observed, while on the subsequent days and on the day after the stimulation a marked suppression of plasma cortisol level and a disappearance of its circadian rhythm was noted. It was hypothesized that these changes in the secretion of the hormone were caused by the alteration of catecholaminergic systems in the CNS. To verify this suggestion chemical lesions of the catecholergic systems of the diencephalon were carried out by the infusion of 6-hydroxydopamine (6-OHDA) into the third cerebral ventricle and animals treated in this fashion were subjected to repeated and prolonged electrical mild footshocking (applied during 3 days). The pretreated animals lost the circadian rhythm in cortisol secretion on the days before as well as during and after the electrical stimulation. The animals pretreated with 6-OHDA showed a significant rise of the plasma cortisol level during stimulation. This rise, as the highest daily concentration, occurring within about 1 h after the beginning of footshocking, was significantly accelerated in time with respect to the physiological acrophase, occurring in the early morning hours at the end of prestimulatory days.

On the other hand, the pretreated animals did not show the decrease of plasma cortisol levels on the day after the stimulation, observed in normal non-pretreated ones. It is suggested that the absence of the suppression of plasma cortisol concentration in the animals pretreated with 6-OHDA on the day after the stimulation may be due to the blockade of the ventral noradrenergic bundle innervating the medial basal hypothalamus, while disappearance of the circadian rhythm of cortisol secretion was due to the disturbance in the function of retinohypothalamic projection.
Prolactin effects on basal and gonadotrophin-stimulated progesterone accumulation by PMSG-primed mouse ovaries in vitro
Authors: Jonassen Julie A. , McNeilly Alan S.
Published: December 2008

Abstract. To examine the effects of prolactin (Prl) and human chorionic gonadotrophin (hCG) on progesterone production by murine ovarian explants, immature female mice were injected with 4 IU pregnant mare's serum gonadotrophin (PMSG) to induce follicular maturation. After 24 or 40 h mice were killed, ovaries removed, cut into fragments and maintained as explants for 24 h in the presence or absence of ovine or human Prl (25–2500 ng/ml). None of these doses of Prl affected basal progesterone accumulation into media over 24 h. To determine if Prl could modify the capacity of ovarian explants to respond to gonadotrophin, ovaries were incubated with 25 IU/ml hCG for 3 h after an initial 24 h incubation period with or without Prl. Prl had no effect on basal progesterone accumulation but significantly enhanced hCG-stimulated progesterone accumulation during the 3 h incubation period.

We conclude that Prl does not inhibit but may enhance progesterone secretion by pre-ovulatory follicles in the mouse.
Insulin-like growth factors (IGF) 1 and 2 in human foetal plasma and relationship to gestational age and foetal size during midpregnancy
Authors: Ashton I. K. , Zapf J. , Einschenk I. , MacKenzie I. Z.
Published: December 2008

Abstract. IGF-1 and IGF-2 were measured by specific radioimmunoassay after acid-ethanol extraction of plasma obtained by foetoscopy from 20 normal foetuses aged 15–23 weeks. IGF-1 and IGF-2 levels were 36 ± 11 and 162 ± 55 ng/ml, respectively. In comparison, levels in cord blood were 84 ± 58 and 264 ± 176 ng/ml, respectively, and in adult plasma were 410 ± 106 and 818 ± 272 ng/ml. Both IGF-1 and IGF-2 were in the normal foetal range in a further three foetuses with anencephaly and two foetuses with spina bifida. No sex difference was observed. IGF-1 was positively correlated with foetal body weight (P <0.001), placenta weight (P <0.02) and with body length measured crown-rump (P<0.01) or crown-heel (P < 0.02). No correlation between IGF-2 and body weight, length, placenta weight or gestational age was found.

Both IGF-1 and IGF-2 are present in the human foetal circulation earlier in gestation than has previously been demonstrated, the levels being low throughout this period of gestation in comparison with adult plasma.
Modifications of pars intermedia cells of ovariectomized rats by oestrogen and progesterone
Authors: Ferreira Adriana Beatriz , Celis Maria Ester
Published: December 2008

Abstract. The effects of the ovarian steroids, oestradiol benzoate (EB), and progesterone (P) on the cells of pars intermedia (PI) from chronically ovariectomized rats (CHR-OVX) were analyzed by qualitative and quantitative electron microscopy (EM) at different intervals after steroid injection. The PI cells of CHR-OVX are rich in secretory granules but poor in organelles related to hormonal synthesis. Twenty-four h after EB administration the cells exhibited cytological features indicative of an increased synthetic activity. These included hypertrophy of rough endoplasmic reticulum, cisternae, a moderately developed Golgi complex, and newly formed granules. These features were also observed in PI cells 48 h after EB administration. Thirty-two and 56 h after the treatment, the PI cells showed signs of both increased synthetic and secretory activity. Thus, it was possible to observe a well-developed rough endoplasmic reticulum, and Golgi apparatus, numerous electron-lucent vesicles, and secretory granules in contact with the cell membrane. However, no exocytotic figures were observed. Progesterone administration resulted in considerable modifications of the ultrastructural features of PI cells also indicative of increased synthetic and secretory activity. The greatest modifications were observed in the mornings with changes that were 12 h out of phase with respect to those observed with EB.

Quantitative estimations of the variation in the content of secretory granules of PI cells fully confirmed the qualitative observations described above.

The serum α-MSH concentrations in ovariectomized rats was found to be incresed 24 h after administration of a single dose of EB and thereafter serum MSH exhibited high levels in the afternoon, whereas the values in the morming were lower. In spayed rats, progesterone injection also resulted in an increase of the serum MSH concentration, but with high levels in the mornings and low levels in the afternoons. In conclusion, EB and P induce modifications in the levels of α-MSH as well as in the ultrastructural changes of the PI cells.
Regulation of 11β/18-steroid hydroxylation in newborn rat adrenal cells in primary culture
Authors: Ramirez Leyla C. , Maume Bernard F.
Published: December 2008

Abstract. In newborn rat adrenal cells in primary culture, the level of activity of the 11β/18-steroid hydroxylase system involved in the last step of the corticosteroid biosynthesis is increased by ACTH. A parallel study of 11β- and 18-hydroxylation showed the same apparent Km values (64 μm) for both hydroxylations. The Vmax values differed: 11.5 μg/106 cells/h for corticosterone and 6.9 μg/106 cells/h for 18-hydroxyDOC. A dose response study of the ACTH effect, measured by the bioconversion of deoxycorticosterone to corticosterone and 18-hydroxyDOC, showed maximum hydroxylation with a dose of 2.2 mU of ACTH/ml. Addition of ACTH after several weeks in culture produced a smaller increase in 1 1β/18-hydroxylation. Removal of ACTH after several weeks of treatment produced an immediate decrease in corticosteroid production; readdition of ACTH produced an increase to the previous level in the case of the 22 mU/ml dose, but not in the case of the 2.2 mU/ml dose. The use of actinomycin D demonstrated that ACTH affects mainly the biosynthesis of protein which must be renewed approximately every 24 h. Finally, the effect of pretreatment or co-treatment with various concentrations of the end products of the reaction showed no inhibition or destruction of the I 1β/18-hydroxylating enzyme system. Therefore, the regulation of the 11β/18-steroid hydroxylase system in these cell cultures seems to be accomplished through the induction by ACTH of the transcription involved in the biosynthesis of cytochrome P45011β and the amount of available precursor furnished by endogenous steroidogenesis.
Catecholamines and pituitary function. IV. Effects of low-dose dopamine infusion and long-term bromocriptine treatment on the abnormal thyrotroph (TSH) dynamics in patients with pathological hyperprolactinaemia
Authors: Nicoletti Ildo , Filipponi Paolo , Fedeli Leone , Ambrosi Franca , Giammartino Camillo , Spinozzi Fabrizio , Santeusanio Fausto
Published: December 2008

Abstract. In order to gain further insight into the role of dopamine (DA) in the control of TSH release and to investigate whether an increased or defective DA inhibition on pituitary thyrotrophs may be considered responsible for the abnormal TSH dynamics in pathological hyperprolactinaemia, we examined the effect of low-dose DA infusion on TRH stimulated TSH secretion in normally cycling women and in patients with pathological hyperprolactinaemia. The effect of long-term bromocriptine therapy on TSH dynamics was also evaluated in a selected group of hyperprolactinaemic women.

Fifty-two hyperprolactinaemic patients with no other signs of pituitary or thyroid dysfunction had significantly higher mean TSH serum concentrations and mean TSH peak values after TRH administration than 75 healthy controls. Furthermore, the TSH rises induced by the DA-synthesis inhibitor α-methyl-p-tyrosine (AMPT, 500 mg orally) were enhanced in both prolactinoma and 'idiopathic hyperprolactinaemia' patients as compared with controls. There was a positive correlation between the TRH- and AMPT-induced TSH rises in the hyperprolactinaemic group.

Low-dose DA infusion (0.1 μg/kg min) reduced TSH response to TRH in both regularly cycling women and patients with hyperprolactinaemic amenorrhoea. Long-term bromocriptine therapy (2.5 mg tid over 60– 150 days) not only normalized serum Prl levels, but also reduced the TSH response to TRH in 7 hyperprolactinaemic women who had presented exaggerated TSH responses to the basal TRH test.

These findings confirm that DA plays a physiological role in the inhibition of TSH release, probably at the level of the anterior pituitary. The fact that both low-dose DA infusion and long-term bromocriptine treatment effectively reduced TSH release in hyperprolactinaemic patients seems to indicate that endogenous DA inhibition of pituitary thyrotrophs is reduced rather than enhanced in pathological hyperprolactinaemia.
No effect of treatment with sodium valproate on plasma growth hormone in bromocriptine unresponsive acromegaly
Authors: Nortier J. W. R. , Croughs R.J. M. , Schwarz F. , Thijssen J. H. H.
Published: December 2008

Abstract. Administration of sodium valproate for 6 months at a dose of 300 mg three times daily to 7 bromocriptine unresponsive acromegalic patients who all but one had been treated with pituitary surgery and/or radiotherapy in the past did not result in a significant reduction of the plasma growth hormone (GH) level or in any clinical improvement. It is concluded that sodium valproate is not suitable for the treatment of acromegalic patients who do not show a favourable response to bromocriptine.
Effects of oestradiol and progesterone on pulsatile secretion of luteinizing hormone in ovariectomized ewes
Authors: Tamanini C. , Crowder M. E. , Nett T. M.
Published: December 2008

Abstract. The effect of treatment with oestradiol, progesterone, a combination of the two steroids or no steroids on pulsatile release of luteinizing hormone (LH) was examined in ovariectomized ewes. Beginning 3 days after ovariectomy, 5 ewes were assigned to each of the following treatment groups: 0.7 mg oestradiol, 16 mg progesterone, 0.7 mg oestradiol plus 16 mg progesterone or no steroid. All treatments were administered twice daily for 3 weeks in a 0.5 ml injection of ethanol given sc. After 2 weeks of treatment and 1, 4, 8, 16 and 32 days after the treatment period ended, blood samples were obtained from all ewes at 10-min intervals for a 6-h period. At the end of the 6-h period, 100 μg gonadotrophin-releasing hormone (GnRH) was injected iv and blood samples were collected at 15 min intervals for an additional 5 h to estimate the relative pituitary content of LH. Ovariectomized ewes receiving no steroid presented regular pulses of LH at frequency of four to five pulses during a 6-h sampling period. Treatment with progesterone alone decreased the frequency of pulsatile release of LH to approximately 1 pulse/6 h, but did not affect the amplitudes of the pulses of LH. Recovery of pulsatile release of LH to a frequency of four or five pulses of LH in a 6-h period was complete between 16 and 32 days after treatment ended in progesterone-treated ewes. Oestradiol, administered alone or with progesterone, resulted in a decrease in both the frequency and the amplitude of pulses of LH compared to control ewes and a decrease in GnRH-induced release of LH. In these groups, the GnRH-induced release of LH had returned to normal by 32 days after cessation of treatment. Although frequency and amplitude of endogenous pulses had increased by 32 days post-treatment, neither parameter had returned to normal. These data suggest that oestradiol exerts an inhibitory effect on the pituitary by decreasing the content of LH to a level which precludes pulsatile release of LH. Progesterone, in contrast, may inhibit the frequency of release of pulses of LH by reducing the frequency of pulsatile release of GnRH from the hypothalamus.
Effects of bromocriptine on prolactin release, electrical membrane properties and transmembrane Ca2+ fluxes in cultured rat pituitary adenoma cells
Authors: Johansen P. W. , Sand O. , Iversen J. G. , Haug E. , Gautvik K. M.
Published: December 2008

Abstract. The effects of the dopamine (DA) agonist bromocriptine on prolactin (Prl) release, electrical membrane properties and transmembrane Ca2 + fluxes have been studied in a clonal strain of rat pituitary adenoma cells (GH3). These cells generate Ca2+ dependent action potentials, and produce and secrete spontaneously both Prl and growth hormone. Prl release stimulated by thyroliberin (TRH) and elevated extracellular K+ concentration was completely blocked by bromocriptine, whereas the basal release was only moderately affected. The TRH and K+ evoked Prl release were half maximally inhibited by bromocriptine at 5–10 and 10–50 μm, respectively.

The normal biphasic membrane response to TRH and the depolarizing effect of elevated K+ concentration were not altered by bromocriptine, whereas the Ca2+-spikes in Na+-free solution were suppressed by the drug. We therefore suggest that bromocriptine blocks the voltage sensitive Ca2+-channels of GH3 cells. In agreement with this notion, bromocriptine also suppressed the basal and TRH induced 45Ca2+ efflux from preloaded cells. We conclude that the inhibitory effect of bromocriptine on the voltage dependent Ca2+-channels is an important mechanism responsible for suppression of Prl release.
Thyroxine and triiodothyronine kinetics in cardiac patients taking amiodarone
Authors: Hershman Jerome M. , Nademanee Koonlawee , Sugawara Masahiro , Pekary A. Eugene , Ross Richard , Singh Bramah N. , DiStefano J. J.
Published: December 2008

Abstract. Cardiac patients taking amiodarone, a potent anti-arrhythmic drug, often have supranormal serum thyroxine (T4) levels and normal or mildly reduced serum triiodothyronine (T3) levels. We studied T4 and T3 kinetics and conversion of T4 to T3 in 5 men with recurrent paroxysmal tachycardia before and after 5–6 weeks of therapy with amiodarone (dose 200–800 mg/day). The patients were also receiving various medicines for cardiac disease. Each was injected with tracer doses of labelled T4 and T3; serum samples were processed by TCA precipitation and ethanol extraction. The data were analyzed with the aid of six-compartment model for T4 and T3 kinetics. Mean total body T3 production rate, total body T3 pool size, and conversion of T4 to T3 were all reduced in patients taking amiodarone.
Endemic goitre in the island of S. Miguel (the Azores)
Authors: de Oliveira A. Lopes , Goncalves M. J. , Sobrinho L. G.
Published: December 2008

Abstract. A survey of endemic goitre in the island of S. Miguel (the Azores) was performed. The prevalence of goitre in school-children varied between 11 and 41%. In the most affected region, 16% of the adult males and 48% of the women had goitre, in some cases grade 3. The median urinary excretion of iodine was very low in school-children, varying between 10 and 49 μg I/g creatinine. The reasons for such a low iodine intake in the population of this oceanic island are the scarcity of fish in the diet and, possibly, the leaching of the soil of its iodine content due to high pluviosity.
Mild hyperthyroidism with inappropriate secretion of TSH in postmenopausal women
Authors: Custro N. , Scafidi V.
Published: December 2008

Abstract. In a previous study on the function of the hypothalamus - pituitary - thyroid axis, about 10% of postmenopausal women with the climacteric syndrome were found to have borderline high values of T3 and T4 and signs of pituitary decreased sensitivity to the suppressive effect of increased thyroid hormones.

The present report concerns 5 women in the first phase of their menopause who showed a mild hyperthyroidism under basal conditions and after suppression test with liothyronine. Each patient had borderline increased levels of serum total and free T4 and T3 and a marked TSH responsiveness to exogenous TRH. After liothyronine, the serum levels of T4, FT4, TSH and the responsiveness to TRH-test clearly decreased.

These data suggest an inappropriate TSH secretion with a decreased pituitary sentitivity to thyroid hormones.

These cases could represent a modification of the hypothalamus-pituitary-thyroid axis associated with that of the gonadal axis, secondary to the absence of rapid adaptation of neurotransmitters.
Triiodothyronine increases responsiveness of cultured rat bone cells to parathyroid hormone
Authors: Schmid Ch. , Steiner Th. , Froesch E. R.
Published: December 2008

Abstract. Osteoblast-like cells prepared from calvaria of newborn rats and grown in culture for 1 week show markedly increased ornithine decarboxylase (ODC) activity upon exposure to parathyroid hormone (PTH) for 4 h. Triiodothyronine (T3) increases ODC activity of the cultures in long-term experiments but does not stimulate cell replication. Moreover, PTH responsiveness is enhanced by T3.

Thus, T3 acts directly on bone cells, and the clinical observation of bone sensitization to PTH by thyroid hormones is confirmed at the cellular level.
Effect of angiotensin II on aldosterone and its precursor steroid production in adrenal zona glomerulosa cells from heparin-treated rats
Authors: Uchida K. , Azukizawa S. , Imaizumi N. , Kigoshi T. , Yamamoto I. , Hosojima H. , Morimoto S.
Published: December 2008

Abstract. To assess the nature of the heparin-induced aldosterone deficiency, we investigated the stimulatory effect of angiotensin II (All) on aldosterone and its precursor steroids in adrenal zona glomerulosa cells from heparin-treated rats compared with those in the cells from vehicle-treated rats. Heparin-treated rats had low plasma aldosterone levels, high plasma renin activity and plasma All levels, and normal plasma corticosterone level 6 weeks after the treatment (1500 IU/kg, twice daily). Basal aldosterone production, when corrected to a uniform number of cells per group, was similar in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to All; an increase by 4 orders of magnitude in the threshold dose for All and a decrease in the maximum All-stimulated level. The maximum All-stimulated levels, but not the basal levels, of pregnenolone, corticosterone and 18-OHB production were low in the cells from heparin-treated rats. ACTH caused a similar stimulatory effect on aldosterone production in the cells from heparin- and vehicle-treated rats. The cells from heparin-treated rats had a less sensitive and lower response of aldosterone production to potassium; an increase by one order of magnitude in the threshold dose for potassium and a decrease in the maximum potassium-stimulated level, presumably because of the glomerulosa hyporesponsivness to AII.

These results suggest that our heparin-treated rats have selective impairment of adrenal zona glomerulosa cells,
Plasma calcitonin response to a calcium clamp in endogenous Cushing's syndrome
Authors: Tørring O. , Bucht E. , Thorén M. , Sjöberg H. E.
Published: December 2008

Abstract. Basal and calcium (Ca) stimulated plasma CT concentrations have been studied in 6 premenopausal females with Cushing's disease and 3 premenopausal females with Cushing's syndrome due to an adrenocortical adenoma. Thirteen healhty premenopausal females served as a reference group. A standardized Ca-stimulus was applied to all subjects by means of the 'calcium clamp' technique. Plasma immunoreactive CT (iCT) was determined by RIA using a carboxyl terminal antiserum with 8 pg-eq/ml as detection limit.

The patients with Cushing's disease had normal basal plasma iCT levels and their iCT response during the 2 h calcium clamp was within the reference range in 5 out of 6 patients, the remaining patient showed a slightly exaggerated response. The patients with adrenal adenoma had elevated plasma iCT levels in the basal state but a normal response during the calcium clamp. It is therefore less likely that the bone resorption often seen in Cushing's syndrome is due to CT deficiency.
Relationships between sleep stages and plasma cortisol: a single case study
Authors: Fehm H. L. , Bieber K. , Benkowitsch R. , Fehm-Wolfsdorf G. , Voigt K. H. , Born J.
Published: December 2008

Abstract. The relationship between the plasma cortisol level and sleep stages was investigated in a single male subject across 17 nights. Blood samples were taken every 30 min from 11.00 p.m. until 02.30 a.m. and every 15 min during the rest of the night. Data analyses performed for the whole nights did not give evidence for strong relations between plasma cortisol and sleep stages. Analyses on data of the second part of the night, beginning with the onset of the first cortisol peak, revealed that plasma cortisol was primarily decreasing when rapid eye movement sleep (REM) was present. Sleep stage I and periods of wakefulness were associated with increasing cortisol levels. There was no evidence for a particular EEG event triggering the first rise of plasma cortisol during the night.
Conversion of CSF monomeric growth hormone to large growth hormone with exposure to serum
Authors: Nixon D. Alan , Jordan Richard M. , Tresp Nancy M.
Published: December 2008

Abstract. We have found a dissociation between CSF and serum growth hormone heterogeneity in a patient with suprasellar extension of a growth hormone-secreting pituitary tumour. When CSF was studied using gel chromatography, virtually all the growth hormone eluted as monomeric growth hormone with only 2.4% eluting before albumin as large growth hormone ('big, big' growth hormone). In contrast, the large component comprised 15.4% of the total immunoreactivity in simultaneously obtained serum. When the CSF specimen was incubated with growth hormone-poor serum, the elution pattern changed remarkably with 16% of the total immunoreactivity eluting as large growth hormone causing it to resemble the serum elution pattern.

We also measured growth hormone heterogeneity in the inferior petrosal vein (a site very close to pituitary venous drainage) during inferior petrosal venography in 3 patients. As the growth hormone concentration increased, the percentage eluting as monomeric growth hormone increased, whereas that eluting as large growth hormone decreased. When the growth hormone concentration fell towards baseline, the percentage of growth hormone eluting as monomeric growth hormone fell while that eluting as large growth hormone increased.

Thus, our studies suggest that large growth hormone results from binding of monomeric growth hormone to serum proteins or aggregation of monomeric growth hormone in the presence of protein. Our studies also show that when blood is sampled at a site close to the pituitary, the growth hormone is released primarily as monomeric growth hormone.
Short-term effects of oestradiol and 4-hydroxyoestradiol on gonadotrophin-releasing hormone induced luteinizing hormone secretion by rat pituitary cells in culture
Authors: Emons G. , Ortmann O. , Fingscheidt U. , Ball P. , Knuppen R.
Published: December 2008

Abstract. Dispersed pituitary cells from adult female rats were preincubated for different time periods (0– 12 h) in the absence or presence of 10−9 moestradiol (E2) or 4-hydroxyoestradiol (4-OHE2). Then the media were changed and the cells incubated for 4 h with either vehicle, or E2, or 4-OHE2 and additionally with different concentrations (10−11– 10−7 m) of gonadotrophin-releasing hormone (GnRH). Treatment of pituitary cells with E2 for 4 h (i.e. no preincubation with E2) significantly decreased the LH-response to GnRH at concentrations ≥ 10−10 m of the decapeptide. During a transition time of approximately 10 h (i.e. in cultures preincubated with E2 or vehicle for 2, 4, 6 or 8 h and then coincubated with E2 or vehicle and GnRH for 4 h) no differences between E2-and vehicle-treated cultures were observed. After 14 and 16 h of E2-treatment (i.e. 10 or 12 h preincubation and 4 h coincubation with GnRH) the LH-responses to GnRH in these cultures were significantly higher than in the respective controls. A nearly identical reaction pattern was observed when 4-OHE2 was used instead of E2.

In a second series of experiments dispersed rat pituitary cells were suspended in a carrier gel and continuously perifused with medium, using small chromatography columns. When these cells were exposed for 4 min to 10−9 m GnRH at 60 or 48 min intervals, they reacted with reproducible pulsatile LH-discharges during at least 6 subsequent stimuli with the decapeptide. When E2 (10−9 m) was added to the perifusion medium, the LH-responses to GnRH were significantly reduced, starting 36 min after the onset of E2-treatment. These data indicate: 1) In the rat, the negative oestrogen effect is at least in part directly mediated at the pituitary level. 2) The sensitizing effect of oestrogens on rat gonadotrophs to GnRH is significant already after 14 to 16 h. 3) E2 and the catecholoestrogen 4-OHE2 have the same effects in this system. 4) The negative E2-effect on GnRH-induced LH-release is significant after only 36 min, a finding bringing up the question of a non-genomic mechanism.
Thyroid growth-stimulating immunoglobulins in goitrous disease: relationship to thyroid-stimulating immunoglobulins
Authors: Smyth P. P. A. , McMullan N. M. , Grubeck-Loebenstein B. , O'Donovan D. K.
Published: December 2008

Abstract. Thyroid growth stimulating immunoglobulins (TGI) were assayed in IgG concentrates prepared from human plasma using a cytochemical bioassay (CBA) based on the measurement of changes in glucose-6-phosphate dehydrogenase (G6PD) activity in guinea pig thyroid follicular cells. TGI was present in all 8 patients studied who had goitrous Graves' disease, in 9 who had toxic diffuse goitres with asymmetric uptake on scintigram and/or symptomatic ophthalmopathy and in 4:8 who had toxic uninodular goitre with autonomously functioning nodules. TGI were also present in 34:54 (64%) of patients who had non-toxic goitres. In contrast, TGI were undetectable in 4 patients who had Graves' disease without palpable goitre and in all 18 euthyroid non-goitrous volunteers. Maximum increases in G6PD activity occurred at an IgG concentration of 50 μg/ml in all patients who had goitrous Graves' disease and in 5:7 who had diffuse non-toxic goitres. In contrast, IgG concentrates from 20:27 patients with nodular goitres caused maximum increases in G6PD activity at an IgG concentration of 500 μg/ml. A comparison of the prevalence of TGI with that of thyroid stimulating immunoglobulins (TSI), also measured by CBA, in 63 patients showed that although both stimulators were present in 8 patients who had goitrous Graves' disease they were only simultaneously present in 18:43 (42%) who had non-toxic goitres of various aetiologies. Thyrotrophin receptor antibodies (TRAb) were present in 11/44 (25%) of non-toxic goitrous patients but there was no significant correlation with IgG stimulators in such patients. It is concluded that the finding of IgG stimulators in a variety of thyroid disorders suggests common immunological features in their pathogenesis. The presence or absence of such stimulators and their relative potencies may play a part in determining functional or structural variations between common forms of goitre.
Serum melatonin is not affected by glucocorticoid replacement in congenital adrenal hyperplasia
Authors: Waldhauser Franz , Frisch Herwig , Krautgasser-Gasparotti Alexandra , Schober Edith , Bieglmayer Christian
Published: December 2008

Abstract. Recently a hypothesis has been proposed suggesting a negative feedback in the regulation of cortisol (F) and melatonin (Mel).

To study a possible influence of F on Mel regulation we examined 13 children with congenital adrenal hyperplasia (CAH) on two occasions: once 3 days after cessation of F substitution (group 1; n = 13) and once during treatment with dexamethasone (1 mg/m2/day) and fludrocortisone (0.1 mg/m2/day) (group 2; n = 11) 11 children matched by sex and age served as controls (group 3). While serum 17 OH-progesterone levels, an indicator for the activation of the hypothalamo-pituitary-adrenal axis in CAH, were significantly (P < 0.001) elevated in untreated patients (group 1), serum Mel levels were not different among the 3 groups nor was the diurnal secretion pattern of Mel affected. Nocturnal serum Mel concentrations, however, correlated with the age of the subjects (r = 0.55, P < 0.001 at 23.00 h), displaying high values in early childhood that declined with progressing age.

The presented data do not support the view of a classical feedback mechanism in the regulation of Mel and F in humans. However, it confirms the description of a tremendous fall of nocturnal Mel concentrations during childhood.