bluuebunny/crossref_metadata_2025 huggingface dataset:
Endocrine profile of a long-acting somatostatin derivative SMS 201–995. Study in normal volunteers following subcutaneous administration
Authors: del Pozo E. , Neufeld M. , Schlüter K. , Tortosa F. , Clarenbach P. , Bieder E. , Wendel L. , Nüesch E. , Marbach P. , Cramer H. , Kerp L.
Published: December 2008

Abstract. The pharmacokinetics and the endocrine profile of a new low molecular somatostatin derivative, SMS 201–995, were investigated in a group of 35 normal subjects. Clearance studies (n = 6) for this peptide showed a prolonged half-life in plasma, 113 min, following single sc injections of 50 or 100 μg. Arginine stimulation tests (n = 6) were conducted immediately and 180 min after sc injection of 50 μg of SMS 201–995. The stimulatory effect of arginine on GH and insulin was counteracted by the peptide at the P < 0.001 and P < 0.02 significance level, respectively. Delayed arginine stimulation revealed a persistent blockade of the GH release (P < 0.02), whereas a recovery of the insulin response was observed. Plasma glucagon increments following a standard protein meal (n = 10) were significantly (P < 0.001) inhibited by previous sc injection of 50 μg of SMS 202–995. Pretreatment with 50 and 100 μ of SMS 202–995 sc (n = 9) inhibited (P < 0.001) the stimulatory effect of TRH (200 μg iv) on TSH without modifying basal levels. The injection of 100 μg/h during sleep completely abolished the nocturnal GH peak in 4 volunteers. No rebound rise after decline of the suppressive action on GH was recorded in any of the trials.

Safety chemistries and blood coagulation studies remained normal and no side-effects or untoward reactions were recorded throughout the investigation.

With its high potency, slow plasma clearance, and long action SMS 201–995 may represent a valuable tool in the long-term management of states of inappropriate GH secretion.
Characterization of the α-MSH-like immunoreactivity in blood and cerebrospinal fluid of the rat
Authors: De Rotte A. A. , Verhoef J. , Andringa-Bakker E. A. D. , Van Wimersma Greidanus Tj. B.
Published: December 2008

Abstract. We have investigated the nature of the α-melanocyte stimulating hormone-like immunoreactivity (α-MSH-LI) in blood and cerebrospinal fluid (CSF) of the rat. Blood and CSF from intact animals were subjected to high pressure liquid chromatography (HPLC) followed by a radioimmunoassay (RIA) specific for the C-terminal part of the α-MSH molecule. It appeared that in both body fluids the predomiant α-MSH-LI co-migrated with synthetic α-MSH and not with its des-acetyl or di-acetyl analogues. We conclude that α-MSH is the predominant form of α-MSH-LI circulating in plasma and CSF of rats from our Wistar strain.
Acromegaly and insulin resistance: a case study
Authors: López J. M. Garía , De La Fuente A. , Tomé Ma A. , Mato J. A. Mato , Gaudiero G. Juan , Odriozola A. , Cabezas-Cerrato J.
Published: December 2008

Abstract. Elevated levels of growth hormone (GH) alter both the glucose tolerance and the sensitivity of peripheral tissue to insulin. We have studied the relationship between impaired glucose metabolism and its variations with different plasma levels of endogenous GH in one patient with acromegaly. To do so, we studied the decline in blood glucose concentration, as induced by iv insulin infusion, from a given hyperglycaemic level. With high levels of GH (GH = 120 μg/l), the slope of the straight line representing the decrease in blood glucose after insulin infusion was —0.71, the time required to achieve normoglycaemic levels, 270 min, and the corrected area under the curve representing blood glucose 26070 units2. After 10 months' bromocriptine treatment, GH plasma concentration fell to 8 μg/l, at which point the slope of the straight line was —1.40, the time required to achieve normoglycaemic levels 115 min, and the area under the curve 8956 units2. There was a greater total clearance of glucose when GH levels were lower (1.90 vs 1.00 ml/min/kg), as well as greater elimination of glucose from the extracellular glucose pool (4.02 vs 1.67 mg/min/kg). In conclusion, in this patient the elevated plasma levels of endogenous GH induced insulin resistance. Once GH levels were reduced by the administration of bromocriptine, glucose metabolism improved.
Paired determination of thyroid-stimulating and TSH-binding inhibitory activities in patients with Graves' disease during antithyroid drug treatment
Authors: Kasagi Kanji , Iida Yasuhiro , Konishi Junji , Misaki Takashi , Arai Keisuke , Endo Keigo , Torizuka Kanji , Kuma Kanji
Published: December 2008

Abstract. Sequential changes in thyroid-stimulating antibodies (TSAb) and TSH-binding inhibitor immunoglobulins (TBII) during antithyroid drug treatment were studied in 17 patients with Graves' disease. Before treatment, TSAb and TBII were detected in 17 (100%) and 13 (76.5%) patients, respectively, with a significant correlation between the two activities (r = 0.600, n = 17, P < 0.02). In 9 patients who became euthyroid as early as after 1–4 months of treatment, the TSAb and TBII activities both gradually decreased, and there was a good correlation between the changes of these activities during treatment. Among the 7 patients in whom small changes in TSAb and TBII activities were observed, 4 showed poor control of the thyrotoxicosis during the whole observation period (7 months–2 years).

One patient who showed a marked dissociation between the changes in TSAb and TBII activities developed hypothyroidism, when his TBII became remarkably high. These potent TBII inhibited cAMP production induced by bTSH. These findings indicate that 1) changes in TSAb and TBII activities reflect the clinical course of hyperthyroidism in most patients with Graves' disease, and 2) development of a blocking-type of TBII may induce hypothyroidism in some patients after the treatment.
T3 releasing activity by Graves' sera from Graves' thyroid in vitro
Authors: Hoermann Rudolf , Mueller Reinhard , Saller Bernhard , Mann Klaus
Published: December 2008

Abstract. The insensitivity of Graves' thyroid to stimulation of cAMP formation by TSH as well as Graves' immunoglobulins in vitro is well known. The present study was performed to find out Graves' sera which may induce a final activation i.e. stimulation of T3 release in Graves' thyroid slices despite this insensitivity of tissue and to characterize determinants responsible for the efficiency of those sera.

Out of 20 sera from patients with active untreated Graves' disease 6 were found to stimulate T3 release from Graves' thyroid in vitro. These 6 sera were effective in stimulating different Graves' glands, irrespective of pretreatment with propranolol, thiamazole (methimazole) or thiamazole plus iodine. In contrast, a significant response to bTSH was not observed in any Graves' gland. For comparison, 17/20 of the same sera were able to stimulate T3 release when tested on human goitrous thyroid. Sera which stimulated Graves' slices revealed no higher stimulating activities in goitrous tissue than serum samples which did not. All sera were additionally assessed for TSH binding inhibiting immunoglobulins in a radioreceptor assay. Remarkably, Graves' thyroid stimulating sera had a low or absent TSH binding inhibiting activity.

Thus, hormone release from Graves' thyroid in vitro – in contrast to that from goitrous tissue – could only be activated by a minority of Graves' sera. These Graves' thyroid stimulating sera could be characterized to contain a selected spectrum of biologically active antibodies with a high TSH agonistic potency stimulating in the presence of a negligible TSH binding inhibiting activity. We conclude the qualitative composition of the antibody spectrum in the individual sera, such as the occurrence of so-called 'TSH superagonists', rather than the height of antibody titre as determined by various methods seems to be relevant for their Graves' thyroid stimulating potency.
Stimulatory guanine nucleotide binding protein activity in the erythrocyte membrane of patients with pseudohypoparathyroidism type I and related disorders
Authors: Saito Toshikazu , Akita Yoshiko , Fujita Hiroko , Furukawa Yohtaro , Tsuchiya Yutaka , Yasuda Toshiyuki , Yamamoto Michiko , Kitagawa Teruo , Nakagawa Yuichi , Takehiro Akira , Fujita Takuo , Kodama Soichi , Kuzuya Takeshi
Published: December 2008

Abstract. The activity of stimulatory guanine nucleotide regulatory protein (Ns) in the erythrocyte membrane was assayed by the reconstitution method using plasma membrane of cyc− S49 mouse lymphoma cells in 18 patients with type I pseudohypoparathyroidism (PHP-I), 2 with pseudopseudohypoparathyroidism (PPHP) and 30 normal subjects, in parallel with other clinical parameters. The Ns activity as expressed by per cent of pooled standard (mean ± se) was 78.9 ±6.1 in PHP-I patients, which was significantly lower (P < 0.01) than the value in normal subjects, 99.5 ± 2.4. In PHP-I patients, the Ns activities (Y) were in significant correlation with three clinical parameters examined (X), i.e., with body height in standard deviation score from the mean of the normal population at the corresponding age, Y = 89.4 + 10.4X (r = 0.616, P < 0.01); with urinary cAMP excretion in relation to creatinine [cAMP(nmol)/Cr(mg)], Y = 56.3 + 7.2X (r = 0.501, P < 0.05); and with TSH levels in plasma (μU/ml), Y = 129–3X (r = 0.639, P < 0.01). The Ns activities of PPHP were as low as 53.8 and 60.0. The decrease of Ns activity in the cell membrane may be implicated in the development of the clinical symptoms such as short stature, decrease in urinary excretion of cAMP and latent or manifest primary hypothyroidism in PHP-I and possibly in skeletal abnormality in PPHP.
Cyclic AMP phosphodiesterase activity in mouse pancreatic islets Effects of calmodulin and phospholipids
Authors: Capito Kirsten , Hedeskov Carl Jørgen , Thams Peter
Published: December 2008

Abstract. The activity of cyclic AMP phosphodiesterase in mouse pancreatic islets was investigated. 85% of the total activity was found in a 27 000 g supernatant fraction. The phosphodiesterase activity in the supernatant fraction, but not in the particulate fraction, was stimulated approximately 20% by Ca2+ (10−5m) and calmodulin (1 μm). The Km (cyclic AMP) of the unstimulated enzyme in the supernatant fraction was 20 μm, and the Vmax was 2 nmol/min × mg protein−1. The possible influence of a range of phospholipids was investigated. PI* and PS (150 μg/ml) inhibited the enzyme 20–30% both in the absence and presence of Ca2+/calmodulin, whereas PE, PC and PA did not affect the enzyme activity. ATP (1 mm) did not affect the particulate or supernatant fraction phosphodiesterase either in the absence or presence of Ca2+/calmodulin or Ca2+/phospholipid. It is concluded that, contrary to islet adenylate cyclase, islet cyclic AMP phosphodiesterase may be regulated by Ca2+/calmodulin.
In vitro study of antral gastrin biosynthesis in response to weaning and corticosterone acetate in rats
Authors: Okahata Hiroyasu , Nishi Yoshikazu , Muraki Kotaro , Sumii Koji , Tanaka Ko , Miyachi Yukitaka , Usui Tomofusa
Published: December 2008

Abstract. The effects of weaning (abrupt dietary changes from breast milk to solid food) and corticosterone injection on antral gastrin-like immunoreactivity (G-LI) concentrations and antral G-LI biosynthesis were studied in rats. A single dose of corticosterone acetate was injected in one group of 7 day old rats, and a single dose of physiological saline was injected in another. Each group of rats was divided into two subgroups, one fed only rat breast milk until 25 days old and the other weaned at day 21. In non-corticosterone treated unweaned rats, antral G-LI did not increase. In non-corticosterone treated weaned rats, antral G-LI was constant before weaning, then increased 4-fold to the adult level. In corticosterone treated unweaned rats, the antral G-LI on day 11 was twice than on day 7, and thereafter remained constant. In corticosterone treated weaned rats, antral G-LI increased after corticosterone treatment and increased again after weaning to reach the adult level at day 25. Gel filtration of pulse-chase incubated antral samples with l-[methyl-3H]methionine from unweaned rats without corticosterone administration showed Vo, fraction 19 (Fr. 19) and gastrin-34 (G34) peaks, but no gastrin-17 (G17) peak after 60 min of chase incubation, but at 120 min of chase incubation a G17 peak was present; corticosterone-treated and/or weaned (solid food alone) rat samples showed Vo, Fr. 19, G34 and G17 peaks at 30 min of pulse incubation.
Pulsatile secretion of progesterone from the human corpus luteum: poor correlation with bioactive LH pulses
Authors: Beitins Inese Z. , Dufau Maria L.
Published: December 2008

Abstract. Having previously established that biologically active luteinizing hormone (LH) is secreted in episodic pulsations that vary in relation to the menstrual cycle, we investigated the possibility that a temporal relationship could exist between the bioactive LH pulses and progesterone secretion from the late corpus luteum. In 4 young women blood was withdrawn every 15 min for 8 h. Serum progesterone concentrations fluctuated at a mean frequency of 0.9 h with a wide range of amplitudes (13.8 to 1.7 ng/ml). Serum bioactive LH pulse frequency in contrast was 0.25 pulses/h in all subjects. The pulse amplitude was 18.2 to 12.4 mIU/ml (2nd IRP-hMG). These data reveal that within the 8 h-period studied, progesterone secretory pulses occurred four times more frequently as those for bioactive LH. Therefore it is unlikely that a temporal relationship exists between individual bioactive LH and pulses of progesterone secreted by the late corpus luteum.
Effect of insulin-like growth factors on human foetal, adult normal and tumour pituitary function in tissue culture
Authors: Goodyer Cynthia G. , Marcovitz Sorana , Hardy Jules , Lefebvre Yves , Guyda Harvey J. , Posner Barry I.
Published: December 2008

Abstract. To determine the direct effects of insulin-like growth factors (IGFs) on hormone release by the human pituitary gland, human foetal, adult normal and tumour pituitary tissues were maintained in culture for 2 to 4 weeks and tested with acute (3 h) exposures to different preparations of IGF peptides. Adult normal pituitaries and adenomas were tested with a semipurified preparation of IGFs, free of immunoreactive insulin, containing IGF-I and IGF-II in a ratio of approximately 1:4. Human foetal pituitaries were tested with the semipurified IGFs as well as more purified preparations of IGF-I and IGF-II. Culture media were assayed for hGH, hPrl, hACTH and hLH using specific radioimmunoassays.

Both foetal (n = 16 (No. of pituitaries), 33 (No. of observations)) and normal adult (n = 3, 16) human pituitaries cultures responded to the semipurified IGFs (2–25 ngEq/ml for foetal and 2–4 ngEq/ml for adult pituitaries) with a significant decrease in hGH release compared to basal (P < 0.01) whereas the GH-secreting pituitary tumours showed no effect when tested with from 2 to 25 ngEq/ml (n = 8, 129, ns). The effect of IGFs on human foetal somatotrope activity was dose-related for both the semipurified IGFs (2–25 ngEq/ml, n = 16, 33) and IGF-I or IGF-II (10–100 ng/ml; n = 3, 18).

hPrl release was inhibited in the normal adult (n = 2, 12; P < 0.01) but not in the foetal (n = 2, 9; ns) pituitary cultures by 2–4 ngEq/ml of the semipurified IGFs, while the Prl-secreting pituitary tumour cultures showed variable responses to 3–4 ngEq/ml of the same IGFs preparation (a) suppression: n = 1, 14, P < 0.001; b) no effect: n = 3, 28, ns). hGH release was inhibited in one of the two mixed (GH- and Prl-secreting) tumours examined (n = 1, 10, P < 0.02) and unaffected in the other (n = 1, 14, ns), while hPrl release remained unchanged in both. The IGFs did not alter release of hLH or hACTH by either foetal or normal adult pituitaries.

Conclusions: A semipurified preparation of IGFs directly inhibited hGH release by human foetal pituitaries and hGH and hPrl release by normal adult pituitaries but had no effect on hLH or hACTH secretion. Human foetal somatotropes responded to IGF-I and IGF-II in a similar dose-dependent manner suggesting that, like in the rat, both IGF peptides can have an inhibitory influence on GH secretion. GH- and/or Prl-secreting pituitary adenomas showed a predominant lack of responsiveness to the semipurified IGFs, suggesting that the sensitivity of somatotropes and lactotropes to an IGF inhibitory influence is often abnormal in the tumour state.
Dexamethasone inhibits the effects of oestrogen on the pituitary gland in rats
Authors: Terakawa Naoki , Shimizu Ikuya , Aono Toshihiro , Tanizawa Osamu , Matsumoto Keishi
Published: December 2008

Abstract. The administration of glucocorticoids has been shown to be effective for the induction of ovulation in patients with anovulation. In the present study, we investigated the effects of a glucocorticoid on oestrogen-induced changes in the pituitary gland. A single ip injection of 10 μg oestradiol-17β (E2) in ovariectomized and adrenalectomized rats resulted in a significant increase in pituitary weight and progesterone receptor (PgR) concentration. In these animals, serum LH level was initially suppressed and restored to control level 24 h after E2 injection. However, 1 mg of dexamethasone (Dex) injected before E2, but not after E2 administration, completely inhibited both the increases in pituitary weight and PgR concentration. The restoration of serum LH level 24 h after E2 was also prevented. These antioestrogenic effects of Dex were blocked by ip administration of the synthetic antiglucocorticoid, RU486. Dex treatment alone did not have any effect on E2-induced changes in the dynamics of pituitary oestrogen receptor. Finally, E2-pellet implanted sc in ovariectomized and adrenalectomized rats for 7 days caused marked increases in pituitary weight and PgR concentration. A single ip injection of 250 μg clomiphene citrate (clomiphene) significantly reduced both the pituitary weight and PgR concentration in these animals, but 1 mg of Dex failed to have a similar effect. These results suggest that glucocorticoids antagonize E2 effects on the pituitary by a mechanism different from antioestrogens such as clomiphene. These antioestrogenic effects of glucocorticoid may be involved in induction of ovulation in anovulatory women.
T-suppresor cell defects in euthyroid nonendemic goitre
Authors: van der Gaag R. D. , von Blomberg-van der Flier Mary , van de Plassche-Boers Ella , Kokjé-Kleingeld Marjan , Drexhage H. A.
Published: December 2008

Abstract. Recently it has been suggested that a substantial number of nonendemic goitre cases can be considered as organ-specific autoimmune disorders of the thyroid. Circulating immunoglobulins, probably receptor autoantibodies, stimulating guinea pig thyroid growth in vitro (TGI) can be found in 2/3 of such patients. Defects in the regulatory balance between T-helper (Th) and T-suppressor (Ts) cells have been described in other thyroid autoimmune diseases, such as Graves' disease and Hashimoto goitre. Such defects are thought to play a role in the loss of control over thyroid autoantibody producing B cells. To investigate whether Ts cell defects can also be found in nonendemic euthyroid goitre, we studied their number and function in 15 of such patients. All patients were clinically euthyroid. Eleven were positive for TGI. Circulating T cells, Th cells and Ts/cytotoxic cells were enumerated using monoclonal antibody techniques (OKT3, Leu3a and OKT8, respectively). Suppressor cell function was assessed employing a proliferation assay in which a short-lived population of such cells was removed by a 24 h preculture. A significant difference was found between patients and controls regarding the Leu3a+/OKT8+ cell ratio: 2.74 (sd 0.94) in patients vs 1.75 (sd 0.38) in controls (P < 0.01); the disturbed ratio was mainly due to a decrease in the percentage of OKT8+ cells. The functional Ts cell assay also showed a defect of patient lymphocytes: patient removal index (SRI) was 1.5 (sd 1.0) vs an index of 2.6 (sd 1.2) for healthy controls (P <0.05). A fair correlation between the numerical and functional data on Ts cells was observed. The present data lend additional support to the concept that nonendemic euthyroid goitre can be viewed as yet another organ-specific autoimmune disorder of the thyroid.
Possible role of glucocorticoids in a complement-activated state induced by cobra venom factor in rats
Authors: Nakano Kiwao , Suzuki Seiji , Chanho Oh , Yamashita Kazuo
Published: December 2008

Abstract. Activation of the complement system of adrenalectomized rats with an injection of cobra venom factor (CVF) caused death of the rats within 2.5 h. Morphologically, this activation provoked distinct congestion of the gastric glandular mucosa and pulmonary leukostasis. Pretreatment of the animals with dexamethasone abolished the undesirable responses completely. Injection of CVF to intact rats produced only slight responses, but caused a marked increase in the serum levels of corticosterone. Dexamethasone was found to be replaced by promethazine (H1-antihistamine) or dimethylsulphoxide (scavenger of hydroxyl radicals) but not by indomethacine, ibuprofen (cyclooxygenase inhibitors), deferoxamine mesylate (iron chelator) or imidazole (thromboxane synthetase inhibitor). These results suggest that glucocorticoids protect the animals from the adverse effects of excessive complement activation and that they act as an inhibitor of the production or action of histamine and toxic oxygen products induced by complement activation.
Serum concentrations of 3,5,3',5'-tetraiodothyroacetate (T4A) in subjects with hypo-, hyper- and euthyroidism
Authors: Ramsden D. B. , Crossley D. N.
Published: December 2008

Abstract. Some factors influencing serum 3,5,3',5'-tetradiodothyroacetate (T4A) concentrations were examined in hypothyroid, euthyroid and hyperthyroid human subjects. Serum T4A concentration was shown to be correlated with parameters such as serum, total and free thyroxine (T4) concentrations and thyroxine: thyroxine binding globulin ratio, which are indicative of the availability of T4 for peripheral metabolism. The relationship between T4A and these parameters was not a simple linear one; serum levels of T4A tended to show less variation from the normal range than did serum total T4 in hyperthyroid subjects.
The 24-h cortisol secretory pattern in Cushing's syndrome
Authors: Tourniaire J. , Chalendar D. , Rebattu B. , Fevre-Montange M. , Bajard L. , Mazenod B. , Dechaud H. , Samra A. B. Abou , van Cauter E.
Published: December 2008

Abstract. The 24-h plasma cortisol profile was obtained at 20-min intervals in 18 patients with Cushing's syndrome (10 with Cushing's disease, 5 with adrenal adenoma, 2 with ectopic ACTH secretion and 1 of questionable aetiology). The mean cortisol level was maximum in the case of ectopic ACTH secretion. The coefficient of variation of cortisol levels was subnormal in all except 2 subjects. Periodogram calculations, providing a best-fit curve (B F C) for each profile, showed that the existence of a significant baseline variation is a frequent feature. In certain cases, it is compatible with the persistance of a true circadian rhythm (2 patients with Cushing's disease; 1 patient with adrenal adenoma). The alteration of plasma cortisol pulsatility is much more pronounced in patients with adrenal adenoma than in patients with Cushing's disease. This is consistent with the hypothesis of a predominantly tonic secretion blunting the episodic hormone release. In 9 patients with Cushing's disease, the plasma cortisol pattern was suggestive of a combination of episodic cortisol release under CRF control and of continuous cortisol secretion due to constant stimulation from an autonomous ACTH source. Two cases were possibly of hypothalamic origin, as suggested by the presence of enhanced cortisol pulsatility and of a normal circadian amplitude. The analysis of the 24-h profile of plasma cortisol in Cushing's syndrome contributes to our understanding of the physiopathological mechanisms underlying this disorder and may help the diagnosis of its aetiology.
Aldosterone in panhypopitutarism: dynamic studies and therapeutic effects in Sheehan's syndrome
Authors: Bakiri Fawzi , Riondel Anne M. , Benmiloud Moulai , Vallotton Michel B.
Published: December 2008

Abstract. To appreciate the aldosterone secretion status in panhypopituitarism, the steroid response to stimulation was studied in a homogeneous group of 20 female patients presenting with global hypopituitarism. Specific effects of glucocorticoid and thyroid hormone deficiencies were also assessed by studying the same patients before and after cortisol (F) and cortisol plus thyroid hormone (F + T) substitution. The patients were submitted to two stimulation tests before and after each treatment: the orthostasis test (O-T) and the furosemide test (Furo-T). The results obtained in the 3 situations were compared, each patient serving as her own control. Comparison was also established with the results obtained in healthy women serving as control group. Basal plasma aldosterone levels in the untreated patients were not significantly different from those of the control group (5.43 ± 0.51 vs 7.16 ±0.80 ng/100 ml, mean ± sem). They were significantly lower after F (3.91 ± 0.42) and F + T substitution (3.31 ± 0.23) than those of untreated patients and controls. Response to both stimulations was blunted in the untreated patients (O-T: 14.10 ± 2.81; Furo-T: 9.78 ± 1.35) as compared to the control group (O-T: 26.46 ± 4.67; Furo-T: 23.96 ± 3.30). F treatment did not improve the response to either tests, (O-T: 11.42 ± 2.55; Furo-T: 10.32 ± 1.23). F + T treatment normalized the orthostasis response (20.83 ± 3.59) and increased the response to furosemide which remained, however, lower (15.28 ± 1.83) than in the control group. These results are in favour of a minor role of the pituitary in the regulation of aldosterone secretion. They emphasize the role of thyroid hormones which may act partly directly, partly through their effect on renin secretion.
Growth hormone-releasing factor does not stimulate phosphoinositides breakdown in primary cultures of rat and human pituitary cells
Authors: Escobar Dolores Collado , Vicentini Lucia M. , Ghigo Ezio , Ciccarelli Enrica , Usellini Luciana , Capella Carlo , Cocchi Daniela
Published: December 2008

Abstract. It has been reported that rat growth hormone releasing factor (rat GRF-43), similarly to the two human GRFs (GRF-40 and 44) stimulates adenylate cyclase activity in pituitary cells. Controversial findings have been presented by two different groups on the action of GRF on phosphoinositides (PI) metabolism, a phenomenon linked to Ca++ – mediated intracellular mechanisms. In the work to be reported, we evaluated the accumulation of inositol phosphates induced by GRF exposure in primary cultures of rat and human pituitary cells. Addition of rat GRF-43 to rat pituitary cells at doses up to 1 μm had no effect on inositol phosphates accumulation, while already at a dose as low as 0.05 nm it increased growth hormone secretion in the incubation medium significantly. In the same cell system, TRH, a known activator of PI breakdown, significantly increased [3H]inositol phosphates. In primary cultures of human somatotrophs from acromegalic subjects as in rats, addition of hpGRF-40 and also of TRH did not elicit any modification in the accumulation of [3H]inositol phosphates. Consistent with in vivo findings, both peptides induced a significant release of GH in the medium. Our results show that the GH releasing effect of GRF does not involve the hydrolysis of phosphatidylinositol in normal rat as well as in tumoral human somatotrophs. In addition it appears that the anomalous response of TRH on adenomatous cells from acromegalic patients is differently mediated in respect to the action of the tripeptide on normal lactotrophs and thyrotrophs.
Thyroid glands in patients with Graves' disease are sources of thyrotropin-binding inhibitory (TBI) activity
Authors: del Carmen Arqueros Maria , Niepomniszcze Hugo , Moreno Juliàn
Published: December 2008

Abstract. In order to investigate the main sources of production of Graves' immunoglobulins, 4 women with Graves' hyperthyroidism, which relapsed after withdrawal of methimazole (MMI) therapy, were selected for this study. The patients underwent subtotal thyroidectomy after pre-operative treatment with MMI and Lugol's solution. Seven blood samples were obtained in each patient during surgery from: 1) a peripheral vein, immediately before neck incision; 2) the carotid artery; 3) and 4) the left and right inferior thyroid veins, respectively, before manipulation of the thyroid; 5) and 6) the left and right inferior thyroid veins, respectively, after surgical handling of the gland; 7) a peripheral vein at the end of operation.

Thyrotropin-binding inhibitory (TBI) activity was measured in all samples by a radioligand method. Serum TSH was also measured in those samples.

There was a substantial increment of TBI in the thyroid veins compared with the activity in the carotid artery. The mean TBI was significantly higher after surgical handling of the thyroid lobes. The two lobes from each gland secreted differing levels of TBI, whereas the TSH concentrations were similar in all samples from each individual patients.

We conclude that at least part of the TBI activity in patients with Graves' disease comes from the lymphocytic infiltration of the glands, and that differences in antibody production between the thyroid lobes may explain the difference in TBI activity in their respective thyroid veins.
Development of gastric somatostatin-like immunoreactivity in response to corticosterone acetate and dietary changes in young rats
Authors: Okahata Hiroyasu , Nishi Yoshikazu , Muraki Kotaro , Sumii Koji , Miyachi Yukitaka , Ueda Kazuhiro
Published: December 2008

Abstract. The effects of dietary changes from breast milk to solid food and corticosterone acetate administration on somatostatin-like immunoreactivity (SLI) in the gastric antrum and corpus were studied in young and adult rats. At 7 days of age, a single dose of corticosterone acetate (250 mg/kg of body weight) was injected in one group of rats, and a single dose of physiological saline was injected in another group. Each group was divided into two subgroups; one was fed only rat breast milk until 25 days of age and the other weaned (solid food alone) at 21 days of age. Gastric antrums and corpora were removed at various ages for assay of SLI concentrations by radioimmunoassay. In non-corticosterone treated rats, antral and corpus SLI increased gradually until 20 days of age, and after changing from breast milk to solid food on day 21 antral SLI increased 2-fold to the adult level, whereas corpus SLI remained constant. In corticosterone-treated rats, antral and corpus SLI on day 11 was 5-fold that on day 7, and thereafter remained constant before changing from breast milk to solid food; after weaning (solid food alone) antral SLI increased again to reach the adult level at 25 days of age whereas corpus SLI remained constant after weaning. Prolonged breast milk feeding alone did not influence antral or corpus SLI levels in either corticosterone-treated or non-treated rats as compared to levels on day 20. Gel filtration of antral and corpus SLI from 15 day old corticosterone-treated and non-treated, and 25 day old weaned (solid food alone) and unweaned (breast milk alone) rats showed almost the same results: only one peak coeluted with synthetic somatostatin-14. The resuits suggest that weaning (solid food alone) and corticosterone administration affect the antral and corpus SLI.
Effects of progesterone induced postmaturity on CBG and pituitary-adrenal activities in the rat foetus
Authors: Dupouy Jean Paul , Chatelain Alain
Published: December 2008

Abstract. CBG and pituitary-adrenal activities were investigated in intact rat foetuses, in newborns spontaneously delivered by vaginal way and in postmature foetuses from mothers with delayed parturition caused by daily progesterone injection from day 20 of gestation. The postmature foetuses had lower body weights and higher adrenal weights on day 22, 23 and 24 of gestation than newborns of the same conceptional age. The corticosterone binding capacity of the plasma as well as the binding capacity of CBG for corticosterone decreased in intact foetuses for the last 3 days of gestation and stayed very low in pups from day 0 to day 8 postpartum. These parameters decreased more slowly in postmature foetuses; however, the differences between the latter and intact foetuses or newborns were not statistically significant. Similar evolution occurred in intact pregnant and suckling females as well as in females with prolonged gestation. The fall in CBG activity in normal rat pups and the subsequent rise in free steroids could explain a sharp decrease in plasma ACTH levels as well as the drop in adrenal and plasma corticosterone concentration. In foetuses with prolonged gestation, the same phenomenon did not occur. Stress conditions produced by maintaining growing foetuses in utero and the development of severe jaundice maintained high ACTH levels. In contrast, the fall in adrenal and plasma corticosterone concentrations in spite of the high level of circulating ACTH could be mainly due to the progesterone inhibition of the steroidogenic activity of the foetal adrenals.
The origin of a human chorionic gonadotropin β-subunit-core fragment excreted in the urine of patients with cancer
Authors: Papapetrou Peter D. , Nicopoulou Stamatina Ch.
Published: December 2008

Abstract. Immunoreactive human Chorionic Gonadotropin (hCG), its subunits and hCGβ-core fragment were analyzed, using Sephadex G-100 chromatography, in urine and tumour extracts from four patients with cancer. These patients were selected for investigation because they were excreting proportionally large amounts of the hCGβ-core fragment in their urine. Although 30–85% of the total immunoreactive urinary hCG was hCGβ fragment, traces of the fragment (2% of total hCG) were found in only two of the tumours and none in the other two. The predominant molecular form of hCG in the tumours was intact free β-subunit of hCG. The conclusion is that the hCGβ-core fragment found in the urine of some patients with cancer is not a secretion product of the tumours. This fragment is very likely a peripheral degradation product of the free β-subunit of hCG which is secreted by the tumours.
Serum and urinary oestrone sulphate in pregnancy and delivery measured by a direct radioimmunoassay
Authors: Honjo Hideo , Kitawaki Jo , Itoh Masafumi , Yasuda Jinsuke , Yamamoto Takara , Yamamoto Takao , Okada Hiroji , Ohkubo Tadashi , Nambara Toshio
Published: December 2008

Abstract. Serum and urinary levels of oestrone sulphate in pregnancy and delivery were measured by a direct radioimmunoassay without hydrolysis. The serum and urinary oestrone sulphate increased as pregnancy progressed. The mean level of serum oestrone sulphate increased to the highest peak of 494 pmol/ml at the 35th gestational week and then decreased. The mean level of urinary oestrone sulphate increased to the highest peak of 1.28 μmol/l at the 34th gestational week and then decreased. At vaginal deliveries, the mean level of maternal peripheral serum oestrone sulphate increased hourly at as high a level as 979 pmol/ml. The mean serum level of oestrone sulphate was 204 pmol/ml in the umbilical artery and 145 pmol/ml in the umbilical vein. At Caesarean section, on the other hand, the maternal peripheral serum level of oestrone sulphate averaged 362 pmol/ml. The mean serum levels of oestrone sulphate were 90.7 pmol/ml and 171 pmol/ml in the umbilical artery and umbilical vein, respectively. These results suggest a maternal origin of oestrone sulphate in pregnancy, with fluctuations in the levels being of interest in relation to labour pain.
Testicular plasminogen activators during postnatal development in the rat
Authors: Vihko Kimmo K. , Toppari Jorma , Saksela Olli , Suominen Jyrki J. O. , Parvinen Martti
Published: December 2008

Abstract. In the seminiferous epithelium, Sertoli cells secrete plasminogen activator (PA) under regulation of follicle stimulating hormone, cyclic AMP and neighbouring spermatogenic cells. Recent observations suggest that preleptotene spermatocytes upon their release from the basement membrane of the seminiferous tubule are important regulators of PA secretion. To study further the role of PA's in the seminiferous tubules, we have analyzed the endogenous levels and secretion rates of PA at various ages during postnatal development, and performed biochemical analyses of the types of PA in the testis and spent media from seminiferous tubular cultures. Cyclic secretion of PA started at the age of 28 days, and from 40 days onwards, the high secretion rates were localized in stages VII and VIII of the cycle of the seminiferous epithelium. The secreted PA is most obviously of the urokinase type; both urokinase-type and tissue-type PA-like activities were found in seminiferous tubular homogenates. The increase in testicular PA levels concomitant to the onset of meiosis in the epithelium was due to the urokinasetype PA-like activity.
Goitre epidemiology: thyroid volume, iodine excretion, thyroglobulin and thyrotropin in Germany and Sweden
Authors: Gutekunst R. , Smolarek H. , Hasenpusch U. , Stubbe P. , Friedrich H.-J. , Wood W. G. , Scriba P. C.
Published: December 2008

Abstract. Thyroid volume of 1397 German and 303 Swedish adults were estimated by sonography. Thyroid size of 6–16 year old Germans (n = 619) was determined and compared with findings on palpation. Thyroid volume was more than twice as great in German (21.4 ± 15.6 ml, mean ± sd) than in Swedish adults (10.1 ± 4.9 ml). The echopattern was abnormal in 16% of the Germans and in 3.6% of the Swedes. German children have a thyroid volume ranging from 1.8 ± 0.4 ml at 6 years to 10.8 ± 6.0 ml at 16 years of age. Palpation is by comparison an unreliable method for determining thyroid size. In Germany, the iodine excretion was less in children (n = 619, 39.5 ± 30.5, 34.1 μg I/g creatinine, mean ± sd, median) than in adults (n = 1193, 83.7 ± 94.4, 62.6), (P <0.001) and much lower than that observed in Sweden (adults n = 98, 170.2 ± 93.3, 141.4; 13 year olds n = 113, 172.9 ± 224.1, 124), (P < 0.0001). Serum thyrotropin concentration was significantly higher (P <0.001) in Sweden (n = 62, 1.49 ± 0.82 mU/ml), than in Germany (n = 91, 0.97 ± 0.52 mU/ml), while serum thyroglobulin was increased in Germany (n = 91, 72.6 ± 50.6 μg/l) as compared to Sweden (n = 62, 23.5 ± 17.4), (P <0.0001). These results indicate the goitrogenic effect of iodine deficiency and the continuing need for an effective iodine prophylaxis in the FRG.
Thyroid growth modulating factors in the sera of patients with simple non-toxic goitre
Authors: Wadeleux P. A. , Winand R.J.
Published: December 2008

Abstract. Since 'Thyroid-Growth-Immunoglobulins' are implicated in the pathogenesis of some goitrous thyroid diseases, we have investigated the presence of thyroid growth modulators in the sera from patients with simple non-toxic goitre (diffuse non-toxic goitre and colloid nodular goitre). To detect growth effect, two procedures were employed, both using [3H]thymidine incorporation into DNA. In one procedure, porcine thyroid follicles in suspension were employed. Gamma-globulin (2 mg/ml) from 10/26 of patients with diffuse non-toxic goitre and 8/27 of patients with colloid nodular goitre were found to increase [3H]thymidine incorporation when compared to gamma-globulins from control group. The other procedure used sparsely plated thyroid cells isolated from normal or porcine thyroid gland and from human simple non-toxic goitre. No serum from patients with simple goitre showed greater growth stimulating activity than that of normal individuals. Moreover, using simple goitre cells as target, a lower serum activity was observed in 7/28 of patients with diffuse non-toxic goitre and in 9/30 of patients with colloid nodular goitre. Analogous results were obtained with normal porcine thyroid cells. The lower serum activity of these patients was observed in a wide range of serum concentrations (1 to 15%) and was associated with and inhibitory effect recovered in the gamma globulin fraction. By the two different procedures, we have therefore evidenced the presence of thyroid growth modulators in the sera of several patients with simple non-toxic goitre. The stimulatory effect observed with the thyroid follicles strengthens the implication of thyroid growth stimulating immunoglobulin in the pathogenesis of some simple sporadic non-toxic goitre. The negative effect detected with monolayers of sparsely plated thyroid cells needs further characterization but, at least, it points out the importance of the culture conditions in the interpretation of the results.
The development of thyrotoxicosis (Graves' disease) during immunosuppression for autoimmune haemolytic anaemia
Authors: Thomson J. A. , Wilson R. , Walker I. D.
Published: December 2008

Abstract. A patient is described who developed thyrotoxicosis (Graves' disease) during immunosuppressive therapy for acquired autoimmune haemolytic anaemia. The fact that the two conditions may be associated should be recognised. Long-term immunosuppressive therapy does not prevent the development of immunoglobulins of IgG type postulated to be aetiologically involved in Graves' disease.
Renal tubular reabsorption of calcium in familial hypocalciuric hypercalcaemia
Authors: Kristiansen J. H. , Brøchner-Mortensen J. , Pedersen K. O.
Published: December 2008

Abstract. To investigate the nephron site of the enhanced tubular calcium reabsorption in familial hypocalciuric hypercalcaemia (FHH), the renal plasma clearance of lithium and calcium and the glomerular filtration rate were determined simultanously after an overnight fast in nine FHH patients and ten healthy controls. As the renal plasma clearance of lithium equals the rate of the proximal tubular fluid delivered into the thin descending loop of Henle's loop, the reabsorption of calcium in the proximal and distal tubule, respectively, could be calculated. We found that the FHH patients had a significantly higher fractional calcium reabsorption in the proximal tubule (77.6 ± 4.7 (%) vs 73.3 ± 3.1, P < 0.05). The same held true for the absolute proximal calcium reabsorption (1.49 ± 0.12 (mmol/l) vs 1.07 ± 0.05, P < 0.001). There was a significant linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption (r = 0.70, P < 0.05). The distal tubular calcium reabsorption did not differ in the two groups. Our results therefore suggest that the enhanced tubular calcium reabsorption in FHH takes place exclusively in the proximal renal tubule.
Circulating growth hormone forms in Type 1 diabetic subjects: comparison with normal subjects and acromegalics
Authors: MacFarlane L. A. , Stafford Susan , Wright A. D.
Published: December 2008

Abstract. The molecular forms of growth hormone (GH) in serum from 18 Type 1 diabetic patients with poor metabolic control were analysed using sephadex G-100 chromatography. The profiles obtained were compared with those from normal subjects whose GH secretion was stimulated by exercise and hypoglycaemia and eight acromegalic patients. In the three groups three distinct GH forms were found: little (monomeric), big and big-big-GH. Samples from normal subjects contained 45% little-GH which was less than samples from the diabetics and acromegalics (53% and 65%, respectively, P <0.01). Further samples from normal subjects after the onset of hypoglycaemia showed an increase in little-GH. In the three groups, the higher the proportion of little-GH, the lower the proportion of big-big-GH, while the proportion of big-GH remained similar. In the acromegalics the proportion of little-GH was strongly correlated with the log concentration of serum GH. As little-GH is cleared from the circulation quicker than the larger forms these data indicate that the main component of the frequent surges of GH secretion in poorly controlled Type 1 diabetic subjects is little-GH (monomeric forms). The sustained release of GH found in acromegaly is composed largely of monomeric forms.
Effects of forskolin, luteinizing hormone and prostaglandin F2α on isolated rat corpora lutea
Authors: Baum Monica G. Sender , Ahrén Kurt E. B.
Published: December 2008

Abstract. The diterpene forskolin increased in a dosedependent way cyclic AMP (cAMP) accumulation in isolated corpora lutea from immature rats injected with an ovulatory dose of pregnant mare's serum gonadotropin (PMSG). The cAMP increase was significant already after 1 min of incubation with forskolin, and cAMP continued to rise to a maximum at about 30–60 min, with a clear decrease after 240 min of incubation. The forskolin effect was more pronounced in very young corpora lutea (1-day-old) than in older corpora lutea. There was a clear discrepancy between the marked effect on cAMP accumulation by forskolin and the steroidogenic response when compared with the corresponding effects of LH. Forskolin also increased progesterone production, but this effect was marginal compared with that of LH. Prostaglandin F2α (PGF2α) did not influence the forskolin stimulated cAMP increase. PGF2α has previously been shown to inhibit the stimulatory effect of LH on cAMP formation in this type of corpora lutea. The fact that PGF2α did not inhibit the forskolin stimulated cAMP production indicates that PGF2α does not act directly on the adenylate cyclase.
Identification and measurement of sex hormone binding globulin1 (SHBG) and corticosteroid binding globulin2 (CBG) in human saliva
Authors: Hammond G. L. , Langley M. S.
Published: December 2008

Abstract. Sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) were detected by specific immunoassays in mixed-saliva taken from normal men and women. The immunochemical identity of both proteins was demonstrated by parallelism between dose response curves generated by serial dilutions of saliva and standards in the immunoassays. In addition, the specific removal of both proteins by incubation with steroid affinity-chromatography gels demonstrated the integrity of their steroid binding activity. The mean ± sd concentrations of SHBG (pmol/l) and CBG (μg/l) in mixed-saliva taken from normal volunteers were as follows: men (n = 6) 19 ± 10 and 38 ± 18; women (n = 6) 63 ± 60 and 72 ± 71 and women during late pregnancy (n = 6) 282 ± 168 and 92 ± 80, respectively. The data indicate that the concentrations of SHBG and CBG in saliva represent ∼ 0.1% of plasma concentrations. It is suggested that these proteins pass from the blood to saliva in a non-specific manner, and may influence the steroid content of saliva under certain physiological circumstances.