bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of thyroidal iodothyronine 5'-monodeiodinase by long-acting thyroid stimulator (LATS)
Authors: Wu Sing-Yung , Reggio R. , Florsheim W. , Chopra I. J. , Solomon D. H.
Published: December 2008

Abstract. To evaluate the effect of long-acting thyroid stimulator (LATS) on thyroid iodothyronine monodeiodinating activity, we have studied the in vitro conversion of T4 to T3 by mouse thyroid homogenate comparing tissue from LATS treated (0.1 ml LATS(+) serum, ip, for 3 days) with tissues from LATS(–) Graves' disease patients' serum or normal serum treated controls. Five out of seven LATS(+) sera were shown to stimulate the T4 5'-deiodinase significantly in mouse thyroid. There was no significant correlation between LATS titre and deiodinase activities in the different sera tested. To compare the effect of LATS and TSH (0.2 IU, ip daily), studies were carried out from 12 to 72 h. LATS had a similar latency of 12 h on the stimulation of thyroid deiodinase compared to TSH as reported earlier. However, the conversion activities reached a plateau by 12 h after LATS treatment, while it continued to rise upon daily TSH injection from 24 to 72 h. In addition, TSH caused a marked reduction of thyroid protein and an early peaking in serum T3 and T4 at 12 h, whereas LATS caused no detectable change in thyroid protein and a gradual rise in circulating T3 and T4. The kinetic analysis indicated that LATS-mediated stimulation of T4 5'-deiodinase was, similar to TSH, associated with an increase in maximum velocity (Vmax were 139, 208 and 505 pmol/mg protein/30 min respectively in control, LATS and TSH-treated animals) without a demonstrable change in the apparent Km (approximately 2.0 μm for T4). The present study demonstrated that some LATS-rich sera stimulate thyroid T4 to T3 conversion in mouse. It provides an insight into the mechanism of increased T3 secretion from Graves' thyroid glands.
Phenobarbital enhances pituitary LH release induced by LRH pulses in the ovariectomized rat
Authors: Lambalk C. B. , van Dieten J. A. M. J. , de Koning J. , Schoemaker J. , van Rees G. P.
Published: December 2008

Abstract. In the ovariectomized (OVX) rat, the plasma LH response was measured to a pulse of LRH (1.25 or 5 ng/100 g body weight, ia) given before and 1 h after ip administration of phenobarbital (80 mg/kg body weight). The LH response to the LRH pulses was increased 1 h after phenobarbital.

In a second experiment, the pituitary LH content of OVX rats was measured 1 h after administration of phenobarbital or saline. No difference in pituitary LH content was found.

It is concluded that in the OVX rat, phenobarbital increases the response to a pulse of LRH, presumably by suppressing endogenous pulsatile LRH. This, together with results of earlier experiments, further supports the hypothesis that under conditions where endogenous pulsatile LRH is present, there is always a certain degree of pituitary desensitization or refractoriness and that the removal of this endogenous LRH leads to recovery of pituitary sensitivity to LRH.
Pre-operative treatment of 5 acromegalics with a somatostatin analogue: endocrine and clinical observations
Authors: Spinas G. A. , Zapf J. , Landolt A. M. , Stuckmann G. , Froesch E. R.
Published: December 2008

Abstract. Five acromegalic patients were treated pre-operatively over a period of 1–4 weeks with the somatostatin analogue SMS 201-995. The patients received daily 3 × 100 μg of SMS 201-995 subcutaneously. This schedule resulted in a rapid improvement of the clinical symptoms in 4 out of 5 patients. In these same patients plasma growth hormone concentrations decreased markedly. However, only in one patient were growth hormone concentrations normalized. Plasma IGF I, which was elevated in all patients, was normalized only in this same patient. Tumour volume as determined by thin section CT-scans decreased only in one case by 17%. All tumours appeared extraordinarily soft upon operation. Conventional light microscopy showed no difference between tumours of SMS-pre-treated and untreated patients. Ultrastructural investigation showed the usual heterogeneity.
The role of gonadal steroids in feedback regulation of gonadotropin secretion at different stages of primate development
Authors: Winter J. S. D. , Ellsworth L. , Fuller G. , Hobson W. C. , Reyes F. I. , Faiman C.
Published: December 2008

Abstract. The serum gonadotropin response to castration was assessed in 8 foetal, 2 neonatal, 30 juvenile, and 2 adult rhesus monkeys (M. mulatta). In the 30 castrated juvenile monkeys and 8 sham-operated controls, concentrations of oestrone, oestradiol, androstenedione, dihydrotestosterone, testosterone and 17OH-progesterone were measured in 10 ml serum pools before, one month after, and one year after the surgical procedure. Castration during foetal life (83–137 days gestation) was followed within 48–72 h by a significant rise in serum FSH levels in males, but had no effect on the already high levels in females. Similarly, castration of males during the first post-natal month raised serum FSH and LH into the adult castrate range; however, after 3 months of age serum gonadotropin levels again declined to the normal juvenile range in spite of the open feedback loop. Orchiectomy of pre-pubertal juvenile monkeys (age 3 months–28/12 years) had no immediate effect on serum gonadotropins, but was followed by a delayed rise in FSH (at age 23/12–43/12 years) and LH (at age 27/12–44/12 years) to adult castrate levels. Orchiectomy of older prepubertal (by serum testosterone) or adult males resulted within a few days in a progressive and sustained rise in serum FSH and a more gradual rise in LH. Prepubertal gonadotropin regulation appeared to be sexually dimorphic, since ovariectomy in juvenile females (age 3 months–15/12 years) was followed by generally elevated, if somewhat erratic, serum FSH values, with a secondary rise in both FSH and LH levels at 2–21/12 years. In both sexes, prepubertal castration caused a significant and sustained decline in serum concentrations of oestradiol; castrated males also showed a decline in serum testosterone levels. Although prepubertal castration also caused in both sexes a slight decline in serum oestrone, and ovariectomy a decline in serum androstenedione and dihydrotestosterone, these effects were not sustained one year later, and values were not significantly different from sham-operated controls. Taken together, these data lend support to a model of primate sexual maturation in which the primary regulator of gonadotropin secretion in both sexes during the prolonged juvenile phase is central inhibition of the hypothalamic GnRH regulator. However, during foetal and neonatal life, and again following the onset of puberty, the major modulator of gonadotropin secretion becomes sex steroid-mediated feedback inhibition.
Biological activities of human growth hormone and its derivatives estimated by measuring DNA synthesis in Nb2 node rat lymphoma cells
Authors: Emoto Naoya , Tsushima Toshio , Shizume Kazuo , Tanaka Toshiaki , Saji Motoyasu , Ohba Yoshito , Wakai Kae , Arai Mariko , Ohmura Eiji
Published: December 2008

Abstract. Nb2 cell is a rat lymphoma cell line that responds to lactogens such as prolactin and human growth hormone (hGH) with an increased rate of proliferation. We explored the relationship between the biochemical events induced by hGH and its derivatives and their receptor binding activities. hGH stimulated RNA, DNA and protein synthesis of Nb2 cells as a function of time. Stimulation of RNA and protein was maximal at 2–3 h and 12 h, respectively, after the addition of hGH. DNA synthesis, measured by the rate of [3H]thymidine incorporation, reached a maximum after 18-h incubation with hGH. Stimulation of DNA synthesis was elicited by hGH in a dose-dependent manner between 0.45 and 45 pmol/l. The activity of the 20 K hGH variant in stimulating DNA synthesis was approx 30% of that of hGH. In contrast, S1-hGH, which lacks a sequence of ten amino acids (140–149) of hGH, showed a 3.2-fold greater activity than hGH. F1 (aminoterminal sequence 1–134 of hGH) was only 0.06% as active as hGH, and the activity of F2 (C-terminal 42 amino acid residue of hGH) was less than 0.01%. Both fragment 1–15 and 32–46 were without effect. The relative potencies of these hGH derivatives in stimulating DNA synthesis were similar to their relative abilities to inhibit [125I]hGH binding to lactogenic receptors on Nb2 cell. Nb2 cells provide a suitable model to study the relationship between receptor binding and the biochemical events induced by lactogens.
The relationship of HLA-DR3 and outcome after antithyroid drugs to the IgG subclass distribution of thyroid autoantibodies in Graves' disease
Authors: Weetman A. P. , Cohen Shara B.
Published: December 2008

Abstract. We have examined the IgG subclass distribution of thyroglobulin (Tg) and microsomal (M) auto-antibodies in 31 patients with Graves' disease before and after treatment with carbimazole. IgG1 and IgG2 subclass antibodies were detected before treatment in nearly all patients, and in over a third there was an excess of activity in the IgG3 and IgG4 subclasses. There were significant differences between the IgG subclasses composing Tg antibodies (less IgG 1 and IgG3 but more IgG2 in the latter). Patients who were HLA-DR3-positive had significantly lower levels of IgG4 in M antibodies than in those who were DR3-negative. A variety of changes were found after treatment, and these depended on whether the patient entered remission or relapse. In particular, IgG1 levels of M antibodies were consistently higher in the relapse group, whereas after 1 year in remission IgG4 levels fell, and IgG2 levels rose. These results show preferential production of certain IgG subclasses composing thyroid autoantibodies in Graves' disease which appears to be associated with HLA-DR3 status and the response to antithyroid drugs.
Retrospective revaluation of the significance of thyroid microsomal antibody in the treatment of Graves' disease
Authors: Hamada Noboru , Ito Kunihiko , Mimura Takashi , Ishikawa Naofumi , Momotani Naoko , Noh Jaeduck , Hosoda Yasuhiro , Morii Hirotoshi
Published: December 2008

Abstract. The results of treatment were analyzed in relation to serum microsomal antibody (MCAb) titre before treatment in 1185 patients with Graves' disease. The percentage of patients who had ablative therapy because of poor response to antithyroid drug treatment was significantly greater in those with MCAb haemagglutination test (MCHA) titres greater than 1:25 000. With 131I treatment, the patients with MCHA titres greater than 1:6400 responded significantly less to therapy, although the analysis was done in 146 selected patients with certain defined radiation doses and small goitres. With surgical treatment, the percentage of the patients entering into remission was significantly smaller for patients with MCHA titres greater than 1:25 000, because of an increase in both hypothyroidism and relapses. The incidence of hypothyroidism was significantly higher in patients with marked lymphocyte infiltration and/or lymphoid follicles. The degree of these histological findings in Graves' disease was not marked in spite of high MCAb titre and it was significantly different from that in Hashimoto's disease when analyzed in relation to the MCHA titre.

These data indicate that in Graves' patients with high MCAb titre, remission is difficult to obtain by treatment, and suggest that the significance of MCAb is different in Graves' disease and Hashimoto's disease. The titre in Graves' disease may be one expression of the activity of this disease.
Induction of prolactin receptors in the liver is more closely related to the growth-promoting than to the lactogenic potency of peptides
Authors: Norstedt G. , Husman B. , Mode A. , Eneroth P. , Lewis U.J. , Gustafsson J.-Å.
Published: December 2008

Abstract. The sex differentiated binding 125I-human prolactin (PRL) to rat liver membranes was studied and the present results extend our previous studies on induction of hepatic PRL receptors by growth hormone (GH). In prepubertal female rats, PRL receptor levels are low compared with those in mature female rat livers. Infusion of hGH during one week to 17-day-old female rats resulted in a receptor level typical of adult female rats. The time course of receptor disappearance in male rats treated with hGH was also studied. When the receptor-inducing hormone was removed, receptor levels in hGH-treated male rats returned to the normal level characteristic of male rats after approximately 96 h.

The specificity of various GH-like and PRL-like hormones in PRL receptor induction was studied in hypophysectomized rats. The PRL-like hormones were identified by measuring their potency to displace 125I-hPRL from a receptor preparation obtained from female rat livers, and the GH-like hormones were identified by their potency to increase body weight in hypophysectomized rats. Using similar doses of hormones it was found that in vivo administration of growth-promoting peptides (rGH, hGH, bGH) induced PRL receptors, whereas lactogenic hormones (rPRL, hPL) had a very small or no effect on PRL receptor induction. This suggests that binding to a type of GH receptor is the first step in PRL receptor induction.
Effect of sera from male type I (insulin-dependent) diabetics on human aortic smooth muscle cells in culture
Authors: Järveläinen H. , Rönnemaa T. , Lehtonen A.
Published: December 2008

Abstract. The effects of sera from male type I (insulin-dependent) diabetics in variable metabolic control were studied on the proliferation and the synthesis of hyaluronic acid, collagen and non-collagenous proteins in cultured human aortic smooth muscle cells (HSMCs). Sera from diabetics in poor metabolic control had a decreased growth-promoting effect on HSMCs as compared with that of sera from non-diabetic healthy male controls. The synthesis of hyaluronic acid in HSMCs was increased in the presence of type I diabetic sera, irrespective of the metabolic control of serum donors. The synthesis of collagen by HSMCs was stimulated only by the diabetic sera which were derived from diabetics in poor metabolic control. The synthesis of non-collagenous proteins in HSMCs was not affected by type I diabetic sera. The stimulatory effect of diabetic sera on hyaluronic acid synthesis by HSMCs correlated inversely with plasma HDL cholesterol of serum donors, whereas the effect of diabetic sera on DNA and collagen syntheses in HSMCs showed an inverse correlation with plasma triglycerides of serum donors. Plasma insulin-like growth factor-I did not correlate with the above functions of HSMCs. Addition of insulin and growth hormone directly into HSMC cultures had no effect on the proliferation or synthesis of connective tissue macromolecules of HSMCs. The results suggest that type I diabetic sera contain factors other than insulin, growth hormone or insulin-like growth factor-I that affect the proliferation and synthesis of hyaluronic acid and collagen of HSMCs in culture. The activity of the factors on cell proliferation and synthesis of collagen is related to some extent to the degree of the metabolic control of the diabetics.
Selenium deficiency as a possible factor in the pathogenesis of myxoedematous endemic cretinism
Authors: Goyens P. , Golstein J. , Nsombola B. , Vis H. , Dumont J. E.
Published: December 2008

Abstract. Myxoedematous endemic cretinism is prevalent in African goitre endemies. It has been related to a thyroid 'exhaustion' atrophy occurring near birth. It is proposed that this might result from the low resistance of a fragile tissue to enhanced H2O2 generation under intense thyroid stimulation by thyrotropin. In support of this hypothesis, low selenium and glutathione peroxidase serum levels have been found in the African endemic area of the Idjwi Island (Kivu, Zaire). Serum selenium and plasma glutathione peroxidase were lower in the area of high endemicity of goitre and cretinism (Northern part of the Island). However, only the former difference is statistically significant. These data thus suggest a role of oligoelements and oxygen toxicity in the pathogenesis of endemic cretinism.
Effect of oral morphine and naloxone on pituitary-adrenal response in man induced by human corticotropin-releasing hormone
Authors: Allolio B. , Schulte H. M. , Deuβ U. , Kallabis D. , Hamel E. , Winkelmann W.
Published: December 2008

Abstract. To further investigate the role of opioids in the regulation of the pituitary-adrenal axis we studied the effect of morphine and naloxone on human corticotropin-releasing hormone (hCRH)-induced ACTH, immunoreactive (ir) β-endorphine, and cortisol release in normal subjects. Protocols: 1. 30 mg of a slow-release preparation of morphine or placebo was given orally 3 h prior to administration of hCRH (0.1 mg iv) (N = 7). 2. Naloxone (4 mg as bolus iv) or placebo was given 5 min prior to hCRH (N = 7). 3. Naloxone (4 mg iv as bolus followed by a continuous infusion of 6 mg over 75 min) or placebo was started 15 min prior to hCRH (N = 6). hCRH was injected at 11.00 h (protocol 1, 2) or at 17.00 h (protocol 3). Oral morphine not only suppressed basal hormone levels (P <0.02), but also the peak response to hCRH compared with placebo (cortisol: 270 ± 50 vs 559 ± 80 nmol/l; ACTH: 5.1 ± 1.5 vs 13.1 ± 2.7 pmol/l; ir β-endorphin: 48.5 ± 8.7 vs 88 ± 14 pmol/l; mean ± sem, P <0.02). Similarly, the maximum incremental changes and the area under the curve were significantly reduced for all three hormones compared with placebo (P < 0.05). After 4 mg of naloxone in the morning, no significant hormonal changes in response to hCRH were observed. However, 10 mg of naloxone in the afternoon led to higher maximum hormone concentrations in response to hCRH compared with placebo (cortisol: 636 ± 30 vs 437 ± 63 nmol/l; ACTH: 19.6 ± 4.4 vs 8.7 ± 1.1 pmol/l; ir β-endorphin: 180 ± 44 vs 94 ± 18 pmol/l, P <0.05). The effect of high-dose naloxone on the hCRH-induced hormone release alone supports the concept of a physiologically significant inhibition of the ACTH release by endogenous opioids via receptors of relative naloxone resistance (δ- or κ-receptors) located at the pituitary level. The μ-agonist morphine may act at suprahypophyseal sites by inhibition of CRH potentiating factors.
Repeatability of C-peptide response in glucagon stimulation test
Authors: Sarlund H. , Siitonen O. , Laakso M. , Pyörälä K.
Published: December 2008

Abstract. Measurement of the plasma C-peptide level before and after iv administration of 1 mg of glucagon was repeated four times in 10 elderly non-diabetic subjects and in 20 elderly non-insulin-dependent diabetics treated with diet or oral drugs to assess the repeatability of the C-peptide responses. Plasma C-peptide levels before and after glucagon administration and C-peptide glucose ratios in the four measurements did not differ significantly from test to test either in diabetic or non-diabetic subjects. The results of the present study indicate that the repeatability of C-peptide response to glucagon is very good both in non-insulin-dependent diabetics and in non-diabetic subjects.
Thyrotropin-releasing hormone immunoreactivity in human blood, urine, spinal fluid, amniotic fluid, saliva, and gastric juice
Authors: Suhonen-Malm Anna-Stina
Published: December 2008

Abstract. TRH immunoreactivity levels were measured in human blood, urine, saliva, spinal fluid, amniotic fluid and gastric juice. Urinary TRH excretion during a 48-h period was measured in 11 healthy persons. Blood and urinary TRH immunoreactivity were measured at 2 and 5 h, respectively, after administration of 40 mg of TRH. All the samples were prepurified by SP-Sephadex-C-25 cation-exchange chromatography and subjected to reverse-phase high-pressure liquid chromatography (HPLC). TRH immunoreactivity levels were then measured by our TRH radio-immunoassay. The TRH immunoreactivity (TRH-ir) levels found in urine were 14.6 ± 2.5 pmol/l; in blood 7.5 ± 2.0 pmol/l; in spinal fluid 2.8 ± 1.4 pmol/l, and in gastric juice 23.2 ± 7.1 pmol/l. In all of the amniotic fluid and saliva samples, in almost one half of the blood and spinal fluid samples, and in almost one third of the gastric juice samples, TRH-ir was below the detectable limit. In blood and urine samples taken after oral administration of TRH, TRH-ir was eluted at the same time as synthetic TRH. The recovery of synthetic TRH added to the samples ranged from 36 to 99%. In all of the biological fluid samples, endogenous TRH-ir was eluted at the same time in HPLC, at 15–18 min, as was synthetic TRH which had been added to the samples. Urine was found to contain two TRH immunoreactive peaks, the second of which was eluted at the same time as synthetic TRH. No diurnal variation in urinary TRH excretion or TRH-ir levels was found. The levels of TRH-ir measured in blood, urine, spinal fluid and amniotic fluid are lower than most of those reported earlier. This study suggests that our method can be used to measure TRH immunoreactivity more accurately in a variety of biological fluids.
Effect of serotonin on basal and TRH-induced release of prolactin from rat pituitary glands in vitro
Authors: Apfelbaum Marta E.
Published: December 2008

Abstract. The effect of serotonin on the release of prolactin (PRL) was studied in vitro. Anterior hemipituitary glands from ovariectomized rats were incubated for 1 h in the presence of different doses of serotonin. Serotonin added into the culture medium caused a significant increase in basal PRL release. The effect was dose-related between 10 and 30 nmol/l serotonin, but responsiveness declined towards basal levels with higher concentrations. When studied as a function of incubation time, basal release of PRL was significantly increased up to 1 h but decreased thereafter. Serotonin also enhanced the release of prolactin induced by 30 nmol/l thyrotropin-releasing hormone (TRH), at all doses tested. A serotonin concentration of as little as 30 nmol/l was already effective. A significant response was seen at 15 min and further increases occurred during the following incubation periods. Serotonin (approximately EC50 4.6 × 10−8 mol/l) was less potent than TRH (EC50 about 1.2 × 10−8 mol/l) to increase basal PRL release. On the other hand, the indole amine appeared to act with similar potency in stimulating PRL release both basal and TRH-induced. In addition, the combined effect of the releasing agents was found to be additive. These results suggest that serotonin and TRH could act through separate mechanisms. Methysergide, a serotoninergic blocking agent, had no effect on the in vitro PRL release either basal or TRH-induced, but it completely blocked that evoked by serotonin suggesting that serotonin may interact with specific receptors on the lactotropes. These findings clearly demonstrate that serotonin may stimulate the release of PRL by acting directly at the pituitary gland level.
Heterogeneity of human luteinizing hormone. Effect of neuraminidase treatment on biologically active hormone and α- and β-subunits
Authors: van Ginkel L. A. , Loeber J. G.
Published: December 2008

Abstract. By preparative isoelectric focussing of a highly purified LH preparation in a sucrose density gradient, four biologically active LH components were isolated. The effect of neuraminidase treatment of each component on the charge heterogeneity was studied by isoelectric focussing followed by in vitro biological and immunochemical techniques. The number of biologically active components with pI-values > 7 containing varying amounts of sialic acid is at least six. The pI-value of the most basic (= asialo) LH component was 9.26. The two most basic components were not present in our preparation (NM 14) before neuraminidase treatment. It is concluded that the difference between the pI-values of LH components is caused by a difference in sialic acid content. When an intact LH component was incubated with neuraminidase there was detectable dissociation owing to the elevated temperature (37°C) and necessary acidic conditions of the incubation. Under these conditions we found the same subunits as we have described before. The most basic α-subunit had a pI-value of 9.29, whereas two β-subunits with pI > 9 were observed at pI 9.26 and pI 9.9. On the other hand, when an LH component was forced to dissociate by incubation at 56°C prior to neuraminidase digestion, two additional α-subunits were found. From this it is concluded that in the intact LH molecule, some sialic acid residues are poorer substrates for neuraminidase action than in the free subunits.
Cholinergic mediation of growth hormone secretion induced by thyrotropin-releasing hormone in cirrhotic patients
Authors: Volpi R. , Chiodera P. , Cerri L. , Roberti G. , Salati G. , Ferrari P. , Delsignore R. , Pedretti G. , d'Amato L. , Coiro V.
Published: December 2008

Abstract. In order to evaluate the possible involvement of muscarinic cholinergic receptors in the GH response to TRH in patients with liver cirrhosis, 8 males with post-hepatitic cirrhosis and 11 males with postalcoholic cirrhosis were primed with the anticholinergic agent pirenzepine and tested with TRH. In addition, 10 male patients affected by piecemeal necrosis were tested in a similar manner. High basal concentrations of GH were found in all groups. None of the patients with piecemeal necrosis responded to TRH, whereas in patients with post-hepatitic and in post-alcoholic cirrhosis, TRH induced a significant rise in GH levels. The priming with pirenzepine (40 mg given iv 10 min before TRH) completely blocked the TRH-induced GH increase, but did not affect the TRH-induced TSH release. These data suggest that a muscarinic cholinergic pathway is involved in the anomalous response of GH to TRH in patients with liver cirrhosis. The lack of effect of pirenzepine on the TRH-stimulated TSH release suggests that the muscarinic cholinergic mediation is peculiar for the effect of TRH on GH secretion.
Effect of naloxone on the development of the positive feed-back action of oestrogen-progesterone on LH secretion in rats
Authors: Faigón María R. , Szwarcfarb Berta , Scacchi Pablo , Moguilevsky Jaime A.
Published: December 2008

Abstract. The purpose of this study was to examine the role of opiate peptides in the development of the positive feedback effect of ovarian hormones (Oe-P) on the LH secretion that matures in female rats at about the age of 20–22 days. Oe-P administration at the age of 14 days induced a significant decrease of LH levels. A single injection of naloxone (5 mg/kg) induced a significant release of LH. This release was completely blocked by Oe-P administration. At the age of 20 days, Oe-P did not induce any significant change of LH levels, whereas naloxone increased the serum LH concentration. On the other hand, injection of Oe-P into naloxone-treated rats induced a significant rise in LH that was significantly higher than that observed with naloxone alone (P <0.025). Oe-P administration induced a positive feedback effect on LH at the age of 25 days. At this age, naloxone also increased LH levels and a significant potentiation of the LH release in response to Oe-P was observed in a group treated with naloxone. These results indicate that naloxone advances the development of the positive feedback mechanism of ovarian hormones on LH secretion and potentiates this mechanism after its maturation. On this basis it is proposed that the probable inhibitory effect of opiates on the onset of the positive feedback mechanism is related to the well-known participation of the opiate system in the onset of puberty. The LH release in response to naloxone significantly decreased from day 14 to day 25 and this could represent a decrease in the inhibitory effect of opiate peptides on LH secretion, probably connected with the onset of the postive feedback mechanism.
Reduced ovarian follicular development as a consequence of low body condition in ewes
Authors: McNeilly A. S. , Jonassen J. A. , Rhind S. M.
Published: December 2008

Abstract. The effect of body condition on ovarian follicular development was investigated in Scottish Blackface ewes in high and low body condition. Follicles were dissected from ovaries on days 11 and 12 of the luteal phase and 24 h after prostaglandin-induced luteal regression. Ewes in low body condition had a lower ovulation rate (low: 0.9; high: 1.8 P < 0.05) and lower mean plasma levels of FSH during both the luteal (low: 54; high: 72 μg/l) and follicular (low: 34; high: 43 μg/l) phases of the cycle. Low body condition was associated with a reduced number of large (⩾ 4 mm) follicles in both the luteal and follicular phases, and in low condition a lower proportion of these follicles was oestrogenic and potentially ovulatory as assessed by follicular fluid levels of oestradiol. However, within the different oestrogenic classifications of these large follicles there were no significant differences in the steroidogenic capacity as assessed by the concentrations of either oestradiol or testosterone in follicular fluid, basal and hCG-stimulated testosterone production, thecal 125I hCG binding or basal and testosterone-stimulated oestradiol production by granulosa cells in relation to body condition. These results suggest that body condition influences ovulation rate by altering the concentration of FSH in blood, which in turn affects the number of potentially ovulatory follicles growing beyond 4 mm.
Pharmacokinetics of methimazole in children and adolescents with Graves' disease
Authors: Okuno Akimasa , Yano Koichi , Inyaku Fumie , Suzuki Yutaka , Sanae Nobutaka , Kumai Megumi , Naitoh Yoshihiro
Published: December 2008

Abstract. Methimazole concentrations in plasma and in the thyroid glands were measured by means of high-performance liquid chromatography. Pharmacokinetics of methimazole were studied after a single oral dose (175 μmol/m2) in nine children and adolescent who were in the thyrotoxic state. Plasma levels of methimazole showed peak concentrations of 4.4 to 12.6 (median 9.2) μmol/l at 0.5 to 4 h after drug administration. Plasma half-life, area under the curve, and distribution volume ranged from 2.73 to 6.04 h, 32.8 to 77.9 μmol · l−1 · h−1, and 0.516 to 0.913 l/kg, respectively. These pharmacokinetic parameters showed a wide variation among the patients, but were quite reproducible in the same subject. Intrathyroidal concentrations of methimazole were measured in another nine subjects including four adolescents and five adults who underwent thyroidectomy. The drug concentrations in the thyroid glands ranged between 3.5 and 23.8 μmol/kg tissue and were far higher than those in the plasma obtained at the time of surgery. In this series of experiments, the dose of the drug varied from 76 to 319 μmol/m2, time after the last dose to surgery from 5 to 24 h, and the mode of drug administration from a single to three divided doses. Among these variable factors, only the daily dose of methimazole corrected by body surface area showed significant correlation with the intrathyroidal concentration, whereas the time after the last dose of the drug and the mode of drug administration did not. Our results revealed that methimazole was concentrated in the thyroid gland and that the intrathyroidal concentrations were maintained for 16 to 24 h in spite of a short plasma half-life. It is suggested that a single daily dose of methimazole is adequate for the treatment of Graves' disease in children and adolescents.
Evidence for an androgen receptor in porcine Leydig cells
Authors: Isomaa Veli , Orava Mauri , Vihko Reijo
Published: December 2008

Abstract. Cytosol and nuclear androgen receptor concentrations were measured in freshly prepared and cultured Leydig cells of immature pig testis with exchange assays using [3H]methyltrienolone as labelled ligand. Androgen receptors in Leydig cells had high affinity for [3H]methyltrienolone and steroid binding specificity typical of an androgen receptor. The mean receptor concentrations were 76 fmol/mg protein and 210 fmol/mg DNA for cytosol and nuclei, respectively. In sucrose gradients, cytosol androgen receptors sedimented in the 4 S region. The cells maintained androgen receptors under culture conditions. Exposure of cultured cells to [3H]methyltrienolone (10 nmol/l) resulted in accumulation of androgen receptors in the nuclei with maximal uptake by 1 h. We conclude that methyltrienolone binding sites with characteristics of androgen receptors were identified in both cytosol and nuclei of porcine Leydig cells.
The influence of naloxone on exercise-induced increase in plasma pituitary hormones and the subjectively experienced level of exhaustion in healthy males
Authors: Bramnert Margareta , Hökfelt Bernt
Published: December 2008

Abstract. Opioid peptides seem to play a role as modulators of the pituitary function in man. In the present study, the effect of naloxone on exercise-induced pituitary hormone release and the subjectively experienced level of exhaustion were investigated in nine healthy males. A submaximal work test was performed on two occasions using a bicycle ergometer: 10 min on 50% of maximal working capacity (MWC), immediately followed by 10 min on 80% of MWC. Ten min before exercise, each subject received, in a single-blind randomized order, either a bolus dose of naloxone (100 μg/kg) followed by a slow infusion of naloxone (50 μg · kg−1 · h−1) or as a control a corresponding volume of the preservatives in the naloxone preparation as a bolus dose followed by an infusion of diluted preservatives. In the control studies, exercise induced a significant increase in GH, PRL, TSH and ACTH. The increase in ACTH was enhanced following naloxone. Naloxone was without effect on exercise-induced changes in GH, PRL and TSH. An increased level of exhaustion was experienced on 80% of MWC during naloxone. It is concluded that opioid receptors with a moderate sensitivity to naloxone are involved in the regulation of the ACTH response to exercise and also influence the subjectively experienced level of exhaustion.
Increased creatine kinase activity in pituitary tumours of rat and man
Authors: Silverlight J. J. , Prysor-Jones R. A. , Hoffman J. , Jenkins J. S.
Published: December 2008

Abstract. The demonstration that phosphocreatine is used as an energy source by rat PRL-secreting pituitary tumours prompted the study of the enzyme creatine kinase in both rat and human pituitary tumours. Rats treated with diethylstilbestrol developed greatly enlarged pituitaries and hyperprolactinaemia. Total creatine kinase was significantly increased and fractionation on diethylaminoethyl Sephadex showed that the 'brain' form was increased, whereas the 'muscle' and mitochondrial forms showed no change. Exposure to large concentrations of oestradiol caused similar changes in creatine kinase which increased over a period of 25 weeks. The total creatine kinase content of a series of human pituitary tumours was highly variable, but the mean value of 183 ± 46 (sem) units per gram protein was significantly higher than the mean for normal pituitary tissues (28.4 ± 2.9). The brain:muscle isozyme ratio was measured in six human PRL-secreting tumours with a mean of 3.47 ± 0.73, significantly higher than in 'non-functional' tumours (1.57 ± 0.29) or normal tissue (1.77 ± 0.28). Three of four GH-secreting tumours had a ratio below 0.6. The highest ratio found (8.66) was in an ACTH-secreting tumour. Previous reports have shown that oestradiol rapidly induces brain creatine kinase in oestrogen responsive tissues. This is not the case with the rat pituitary gland or oestrogen responsive human tumour cells in culture. Chronic oestrogen treatment, however, does increase creatine kinase in the proliferating gland and many human pituitary tumours have increased enzyme activity. These results suggest that the phosphocreatine/ATP system and in particular the brain isozyme of creatine kinase are of particular importance in lactotropes.
Insulin, ketones, glucose and glucagon:
Authors: Ledet Thomas , Heickendorff Lene
Published: December 2008

Abstract. The influence of insulin in physiological concentrations on basement membrane (BM)-like material from arterial smooth muscle cells was studied in cell cultures. BM-like material was isolated from the cell layer by a sonication-differential centrifugation technique after a 24-h incubation period with insulin and [3H]leucine added to the culture medium. Insulin in concentrations of 50, 100, 200 and 500 mU/l was found to exert no influence on incorporation of amino acids into BM-like material. Neither glucose, 16 mmol/l, ketones, 1 mmol/l, nor glucagon 100 ng/l were able to induce altered accumulation of BM-like material. The effect of insulin on the carbohydrate units of BM-like material was studied by concanavalin A-Sepharose chromatography of glycopeptides and by analyses of neutral hexoses and amino sugars. The result showed that insulin, 200 mU/l, induced a shift in composition of neutral sugars by decreasing the amount of galactose relative to glucose and mannose. No changes in glycopeptide binding to the concanavalin A-sepharose column were observed. The results indicate that insulin induces only minor alterations in BM-like material of arterial smooth muscle cells and that the changes apparently are restricted to the carbohydrate units.
The effect of the somatostatin analog SMS 201-995 on normal growth hormone secretion in the rat.
Authors: Lamberts Steven W. J. , Verleun Theo , Zuiderwijk Joke M. , Oosterom Rob
Published: December 2008

Abstract. The somatostatin analog SMS 201-995 was recently shown to be effective in suppressing GH secretion and in causing tumour shrinkage in patients with GH-secreting pituitary tumours. In this respect, the action of SMS 201-995 seems similar to that of the dopamine-agonist bromocriptine in patients with PRL-secreting pituitary tumours. In the present study we compared the respective effects of SMS 201-995 and bromocriptine on normal rat GH and PRL release in vivo and in vitro. Both in vitro and in vivo, repeated administration of SMS for up till 6 days suppressed circulating GH concentrations, and the ability of the pituitary glands to release GH in vitro. A dose-dependent diminution occurred of the total pituitary GH content in rats treated in vivo with SMS 201-995 for 4–6 days. During short-term in vitro incubation for only 4 h, the total amount of GH measured in the medium + gland was also diminished. Chronic administration with SMS 201-995 (2 μg/kg twice daily for 15 days), however, resulted in a complete desensitization of its inhibitory effect on GH synthesis and release. In similar experiments it was shown that the dopamine agonist bromocriptine affects normal PRL secretion in a different manner. Both in vitro (10 nmol/l) and in vivo administration for 6 days (0.2 mg/kg twice daily) greatly inhibited circulating PRL levels and the ability of the pituitary glands to release PRL in vitro. This is, however, in all instances accompanied by an accumulation of PRL within the pituitary gland. Long-term bromocriptine administration (0.2 mg/kg twice daily for 15 days) inhibited PRL secretion, and finally also a decrease in the total pituitary PRL content was observed. It is shown in this study that SMS 201-995 and bromocriptine affect hormone release by normal pituitary glands in a different manner. SMS 201-995 acutely inhibits GH release and diminishes within a few hours of exposure also the GH content in normal cells by a powerful inhibition of GH synthesis and/or an increase in intracellular degradation of GH. Bromocriptine, however, exerts primarily an inhibitory effect on PRL release, whereas an inhibition of synthesis and/or degradation of intracellular PRL is evident only after long-term exposure to the drug.
Existence and immunological significance of circulating Ia+T cells in autoimmune thyroid diseases
Authors: Zeki Kazuya , Fujihira Takashi , Shirakawa Fumihiko , Watanabe Kenichi , Eto Sumiya
Published: December 2008

Abstract. We investigated the percentage of circulating HLA-DR antigen positive (Ia antigen positive: Ia+) T cells and the additive proliferation by non-specific mitogens and thyroid-specific antigens by means of a cytotoxicity test in autoimmune thyroid diseases. Furthermore, we studied the stimulative function of circulating Ia+T cells in autologous mixed lymphocyte reactions. %Ia+T cells were significantly increased in patients with autoimmune thyroid diseases compared with those in normal controls. They were additionally increased by the stimulation of TSH-receptor or thyroid-microsome in patients with Graves' disease, and by the stimulation of thyroglobulin and thyroid-microsome in patients with Hashimoto's thyroiditis. As to the cellular immune function, circulating Ia+T cells stimulated Ia− T cells in autologous MLR in patients with autoimmune thyroid diseases. These data suggest that some of the T cells are already activated in vivo, that the activation of T cells may be by thyroid-specific antigens, and that these activated (Ia+) T cells may be able sequentially to induce the activation of inactivated (Ia−) T cells in autoimmune thyroid diseases.
Detection of late-onset adrenal hyperplasia in girls with peripubertal virilization
Authors: Sólyom J. , Gács G. , Keszei K. , Láng K. , Örley J. , Petheö I. , Ságodi L.
Published: December 2008

Abstract. We investigated the value of serum levels of adrenal steroids (dehydroepiandrosterone sulphate, testosterone, 17-hydroxyprogesterone, cortisol) in the identification in peripubertal females with late-onset congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Among 68 females (age 3–18 years) with virilization in childhood, peripubertally or postpubertally, we selected 21 girls for an ACTH test by measurement of basal blood-spot or serum 17-hydroxyprogesterone (17-OHP) levels. Eight of 21 patients had supranormal post-ACTH serum 17-OHP concentration (57–153 nmol/l) with low normal cortisol concentration. All of them had supranormal basal and post-ACTH 17-OHP to cortisol ratios. These data show a relatively high incidence (about 12%) of mild 21-hydroxylase deficiency among prepubertal and adolescent girls with virilization. It is concluded that the first step in the investigation of peripubertally virilized girls should be the determination of serum 17-OHP and cortisol. Patients with basal morning 17-OHP concentration and 17-OHP to cortisol ratio above reference range should be given an ACTH test.
Gastrin in pituitary tumours
Authors: Bardram Linda , Lindholm Jörgen , Rehfeld Jens F.
Published: December 2008

Abstract. Twelve of 87 pituitary adenomas from patients with acromegaly, Cushing's syndrome, Nelson's syndrome, hyperprolactinaemia and without symptoms of hormone hypersecretion contained gastrin in concentrations from 0.5 to 166 pmol/g. Only ACTH-producing tumours contained gastrin, which occurred in forms smaller than those present in the normal adenohypophysis. The results indicate that corticotropic tumours may synthesize gastrin in moderate amounts.
Twenty-four-hour beta-endorphin secretory pattern in the elderly
Authors: Rolandi E. , Franceschini R. , Marabini A. , Messina V. , Cataldi A. , Salvemini M. , Barreca T.
Published: December 2008

Abstract. A chronobiological study was carried out in seven elderly male subjects (78–84 years) to evaluate the 24-h beta-endorphin secretory pattern. Seven young adult males (28–37 years) made up the control group. Blood samples were drawn every four hours from 08.00 to 20.00 h and every two hours from 24.00 to 06.00 h. ACTH and cortisol levels were also determined in the same plasma samples. Mean 24-h beta-endorphin values in the elderly (32.6 ± 1.1 ng/l) and in the young adult male subjects (29.5 ± 1.4 ng/l) did not differ statistically, but the circadian rhythm was absent in the elderly subjects. In the elderly, plasma ACTH and cortisol concentrations showed a circadian rhythm similar to that observed in the adult subjects. However, in the elderly patients, in contrast to that in the adult subjects, the multilinear regression analysis did not show any statistically significant correlation between the beta-endorphin, ACTH and cortisol 24-h plasma concentrations.
Pre-diabetes in the spontaneously diabetic BB/E rat: pancreatic infiltration and islet cell proliferation
Authors: Bone A. J. , Walker R. , Dean B. M. , Baird J. D. , Cooke A.
Published: December 2008

Abstract. A cohort of BB/E rats derived from litters with a high and low incidence of IDDM was studied prospectively to examine the relationship between circulating autoantibodies, islet insulin secretion, pancreatic infiltration, and islet cell replication during the pre-diabetic period. Although a higher incidence of islet cell surface (ICSA) and insulin autoantibodies (IAA) was detected in the diabetes-prone than in the low diabetic-incidence BB/E rats there was no correlation between the two antibodies in individual animals. Moreover, ICSA, but not IAA, were associated with loss of first phase islet insulin release. Between 75 and 105 days of age the number of diabetes-prone rats with ICSA and impaired islet insulin secretory function increased. Over the same period, there was a concomitant increase in the proportion of diabetes-prone animals with pancreatic infiltration, and increased islet endocrine cell proliferation. All these interrelated phenomena were observed in diabetes-prone BB/E rats at a time when the animals were normoglycaemic.
Thymopoietin and thymopentin enhance the levels of ACTH, β-endorphin and β-lipotropin from rat pituitary cells in vitro
Authors: Malaise M. G. , Hazee-Hagelstein M. T. , Reuter A. M. , Vrinds-Gevaert Y. , Goldstein G. , Franchimont P.
Published: December 2008

Abstract. Thymopoietin and thymopentin are well characterized polypeptides influencing immunoregulation by several mechanisms. Proposed as a therapy in diseases with major immune abnormalities such as rheumatoid arthritis, thymopentin improved within 2 weeks some clinical parameters as pain and joint swelling. The hypothesis that this spectacular effect could be mediated through interactions with anti-inflammatory (ACTH) and pain relieving (β-endorphin) hormones producing cells was tested on the rat isolated pituitary cell model. Thymopentin and thymopoietin can enhance in vitro the levels of ACTH, β-endorphin and β-lipotropin in a time- and dose-dependent fashion for physiological concentrations ranging from 10−12 to 10−8 mol/l. The action on pituitary cells was restricted to those molecules as no changes occurred in LH, FSH, GH, TSH and PRL levels, after otherwise identical experimental conditions.
Influence of the environmental temperature on the post-partum testosterone surge in the rat
Authors: Roffi J. , Chami F. , Corbier P. , Edwards D. A.
Published: December 2008

Abstract. In the neonatal male rat, a rapid and transient increase in serum testosterone occurs about 2 h after birth. This post-partum testosterone surge (PPTS) has been implicated in the masculinization and defeminization of the central nervous system. The present study shows that environmental temperature can have a profound influence on the PPTS. Male rats were delivered from their mothers by caesarean section on day 22 of gestation. Immediately thereafter, neonatal males were placed at an ambient temperature of either 18, 21, 24 or 30°C. With 2 h of exposure, the body temperature was in close correspondence with the ambient temperature. The PPTS was clearly abolished in the pups exposed for 2 h at either 18 or 21°C. The effect of temperature was reversible: by placing pups at either 18 or 21°C for 2 h after delivery, and then rewarming by placing them with a foster mother, the PPTS was delayed until 4 h after birth, i.e. 2 h after the beginning of rewarming. Thus, environmental cooling appears to retard the development of neural and/or endocrine systems mediating the PPTS. Aberrant maternal care which would produce substantial cooling of the male pups would be expected to affect the PPTS, which in turn might affect the sexuality of male progeny.