bluuebunny/crossref_metadata_2025 huggingface dataset:
Human and porcine insulins are equally effective in the regulation of glucose kinetics of diabetic patients during exercise
Authors: Koivisto Veikko A. , Pelkonen Risto , Nikkilä Esko A. , Heding Lise G.
Published: December 2008

Abstract. The rate of hepatic glucose production (Ra) and peripheral utilization (Rd) was determined in 8 insulin-dependent diabetic subjects in basal state and during 40 min cycle ergometric exercise. The patients were treated with continuous sc infusion of either semisynthetic human or porcine (Actrapid®) insulin. Basal rate of glucose production was comparable during human (2.29 ± 0.19 mg/kg/min) and porcine (2.18 ± 0.12 mg/kg/min) insulin therapy. In response to exercise, Ra rose 30 to 40% (P < 0.05), to 2.85 ± 0.35 vs 3.18 ± 0.42 mg/kg/min, similarly during both studies. The peak rise in Rd (to 3.20 ± 0.32 during human vs 3.78 ± 0.44 mg/kg/min during porcine insulin) was comparable in both groups and not significantly different from the rise in Ra. Consequently, blood glucose levels remained unchanged. During the exercise tests, the metabolic conditions were stable and comparable in both studies, as indicated by similar levels of blood glucose, plasma free insulin HbA1, serum lipids and insulin binding to erythrocytes.

In conclusion, semisynthetic human insulin is equally effective as porcine insulin in regulating glucose kinetics in the basal state and during exercise.
A neonatal mass-screening for congenital adrenal hyperplasia in Japan
Authors: Shimozawa Kazuhiko , Saisho Sumitaka , Saito Nobuchika , Yata Jun-ichi , Igarashi Yoshio , Hikita Yoshinori , Irie Minoru , Okada Kazuchika
Published: December 2008

Abstract. A pilot neonatal mass-screening for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) was performed in the western region of Shizuoka Prefecture, Japan, using a simplified radioimmunoassay method for 'Disc-17-hydroxyprogesterone (17-OHP)' determination. The results obtained during a 30-month period indicated that 3 infants out of the 34314 neonates examined were proved to have 21-OHD, and the incidence of homozygotes and heterozygotes were estimated to be 1:11438 and 1:54, respectively. At the time of recall, the concentrations of plasma 17-OHP and 21-deoxycortisol and their urine metabolites as well as plasma sodium levels were quite applicable to diagnosis, while the clinical signs that may be manifest in 21-OHD were of little value in this connection. Prematurity and perinatal complications of neonates tended to give false-positive results, being secondary to the function of the residual foetal adrenal cortex and non-specific stimulatory effects of various stresses.

Despite several technical and practical problems to be solved, the present study demonstrated the importance and validity of a neonatal mass-screening program for CAH.
5α-reductase deficiency: diagnosis via abnormal plasma levels of reduced testosterone derivatives
Authors: Corrall R. J. M. , Wakelin K. , O'Hare J. P. , O'Brien I. A. D. , Ishmail A. A. A. , Honour J.
Published: December 2008

Abstract. A case of 5α-reductase deficiency is described who presented clinically as primary amenorrhoea. Plasma levels of the two isomers resulting from the 5α-reduction of testosterone provide a simple method for diagnosing this condition. An intermediate abnormality was found in other family members consistent with the heterozygous state.
Pituitary and gonadal function in pubertal and adult male rabbits with pseudohermaphroditism secondary to immunization of mothers against testosterone
Authors: Veyssière G. , Berger M. , Jean-Faucher Ch. , de Turckheim M. , Jean Cl.
Published: December 2008

Abstract. Pituitary and testicular function was studied in pubertal and adult rabbits with pseudohermaphroditism secondary to immunization of mothers against testosterone. Circulating testosterone, LH and FSH levels showed a developmental pattern during sexual maturation, similar to that observed in controls. Plasma FSH levels were elevated in male pseudohermaphrodites despite normal plasma testosterone concentrations. Fighting, male sexual behaviour and coitus occurred normally as in controls.

The testicular response to endogenous elevated LH levels and the pituitary LH and FSH responses to LRH injection and to castration were similar in affected males and in controls. These observations suggest that inhibition of the central effects of androgens during the embryonic and perinatal period has little or no effect on the differentiation and maturation of the hypothalamo-pituitary-testicular axis in rabbit.
Steroid biosynthesis and Leydig cell morphology in adult unilaterally cryptorchid rats
Authors: Bergh A. , Åson Berg A. , Damber J.-E. , Hammar M. , Selstam G.
Published: December 2008

Abstract. Unilateral cryptorchidism was induced in newborn rats and when the rats reached adult age Leydig cell morphology and steroid biosynthesis were compared in scrotal and abdominal testes. The cell profile area of abdominal Leydig cells was reduced, the cytoplasm contained an increased number of lipid droplets and the endoplasmatic reticulum was more sparse than in scrotal Leydig cells. The intratesticular concentrations of progesterone, 20α-dihydroprogesterone, 17α-hydroxyprogesterone and testosterone were measured both basally and after LH stimulation. The synthesis of testosterone was subnormal in the abdominal testes. The data on basal steroid concentrations suggest a block at the 17α-hydroxylase level, but observations after LH stimulation suggest that earlier steps are also involved. When studied in vitro the steroid biosynthesis in abdominal testes was also disturbed. The conversion mediated by 17α-hydroxylase and 17β-kestosteroid reductase was lower and the conversion mediated by 20α-dehydrogenase was higher in the abdominal testis. The reason for the disturbed steroid biosynthesis in abdominal testes is unknown. It may be related to the increased concentration of oestradiol in abdominal testes. Other possibilities are altered paracrine influence from the damaged tubules or changes in the microcirculation of the testis.
Cross-reaction of serum somatomedin-binding protein in a radioimmunoassay developed for somatomedin-binding protein isolated from human amniotic fluid
Authors: Póvoa Guilherme , Roovete Arved , Hall Kerstin
Published: December 2008

Abstract. A radioimmunoassay was developed for somatomedin-binding protein isolated from human amniotic fluid. The mean level in amniotic samples from 20–22 week of gestation was high, 51 μg/ml. Human serum and serum fraction gave dose-response curves superimposable on that for the pure amniotic binding protein. Gel chromatography of serum at neutral pH disclosed immunoreactive binding protein only in fractions with a molecular size of 35000 corresponding to elution volume for the low molecular form somatomedin-binding protein. The mean levels (mean and range) of immunoreactive somatomedin-binding protein in cord blood (191 ng/ml, 55–1698 ng/ml) and in diabetic patients with uraemia (97 and 51–174 ng/ml) were 5- to 10-fold elevated above those of healthy adults (23 and 18–36 ng/ml). In acromegaly the levels decreased with increasing GH production (r = −0.77; P < 0.005). In adult patients with GH deficiency the levels were 2-fold elevated in comparison with healthy subjects. Apart from patients with uraemia a negative correlation was found in adults between the levels of immunoreactive binding protein and immunoreactive IGF-I which reflect the GH production (r = −0.81, P < 0.001).
Plasma growth hormone (GH) responses to single and repetitive subcutaneous administration of GH releasing factor (hpGRF-44) in normal and GH deficient children
Authors: Takano K. , Hizuka N. , Shizume K. , Honda N. , Ling N. C.
Published: December 2008

Abstract. Synthetic human pancreatic GRF (hpGRF-44) was administered sc to 8 normal children with short stature and 11 patients with GH deficiency. After a dose of 100–200 μg hpGRF-44, mean plasma GH levels reached a peak at 15 min of 27.2 ± 6.4 (± se) ng/ml in normal children. However the responses were variable and peak plasma GH varied from 10.1 to 56.5 ng/ml.

Eight of 11 patients with idiopathic GH deficiency did not respond to sc administration of 100–300 μg hpGRF-44. However, a plasma GH increase of more than 5 ng/ml occurred in 2 patients and to twice the basal level in 1 patient. Their GH values were 14.3, 5.2 and 3.4 ng/ml, respectively. After repetitive administration of hpGRF-44 (200 μg, twice a day) sc for 5 consecutive days, 2 of 8 patients restored their responsiveness, but the remaining patients did not show GH rise in response to both sc and iv bolus administration of hpGRF-44. Repetitive hpGRF-44 administrations for 5 days had no effect on somatomedin-C production.
Activation of the cholinergic system and growth hormone release in the dog: functional interactions with other neurotransmitters
Authors: Betti R. , Casanueva F. F. , Cella S. G. , Müller E. E.
Published: December 2008

Abstract. In unanaesthetized dogs iv administration of the cholinesterase inhibitor eserine (0.5 mg) induced a clear-cut rise in plasma canine growth hormone (cGH) levels. Diphenhydramine and meclastine, two antagonists of histamine (H) H1 receptors completely suppressed the GH-releasing effect of eserine, while cimetidine, an H2 receptor antagonist, only blunted and delayed it. Two long-lasting serotonin (5-HT) receptor antagonists, metergoline and pizotifen, partially or completely suppressed, respectively, GH release evoked by eserine, whereas fenfluramine, a releaser of neuronal stores of 5-HT and hence a functional activator of 5-HT neurotransmission, was ineffective in this context. Pimozide, a long-acting dopamine receptor antagonist, abolished the effect of eserine, whereas domperidone, which has the same pharmacological properties but does not cross the blood brain barrier, failed to do so. Finally, phentolamine, an antagonist of α-adrenoceptors, and propranolol, a β-adrenergic antagonist, were completely ineffective in preventing the rise in plasma cGH levels induced by eserine, as was naloxone, an antagonist of opiate receptors. All these data demonstrate that, although cholinergic mechanisms are involved in the mechanism(s) underlying cGH release, the final common pathway for GH secretion is not cholinergic. Preservation of dopaminergic and H1 neurotransmission, probably within the blood barrier, is needed to allow the neuroendocrine transduction of cholinergic inputs, whereas the role of 5-HT neurotransmission remains uncertain.
A comparison of the effects of propylthiouracil and methimazol on circulating thyroid hormones and various measures of peripheral thyroid hormone effects in thyrotoxic patients
Authors: Laurberg P. , Tørring J. , Weeke J.
Published: December 2008

Abstract. Two groups of patients with newly diagnosed thyrotoxicosis were treated with propylthiouracil (PTU) 400 mg every 6 h for 4 days followed by methimazol (MMI) 40 mg every 6 h for 4 days or by MMI for 4 days followed by PTU for 4 days. The shift from MMI to PTU induced a considerable decrease in serum T3 while shift from PTU to MMI led to an increase in serum T3. Serum T4 decreased gradually during the whole treatment period. The opposite variations in serum T3 were accompanied by similar opposite variations in basal metabolic rate (BMR) (P < 0.001). Hence the rapid variations in serum T3 which can be induced by PTU in thyrotoxic patients, are followed by rapid alterations in the thyrotoxic state as evaluated by BMR.
Development of thyroid autoimmunity
Authors: Aho K. , Gordin A. , Palosuo T. , Takala J.
Published: December 2008

Abstract. Two blood samples were taken at an interval of 5 years in a continuing epidemiological study of a rural population in south-western Finland with an age range of 40–64 years at commencement. Paired sera of 680 subjects were tested for antibodies against thyroglobulin and thyroid microsomal antigen. In the seroconversion cases the titres in the second specimens were either low or medium but never high. In the cases selected on the basis of the highest titres in the follow-up specimens, the titres in the baseline specimens were either high or medium but never low. These findings suggest that the emergence and the development of thyroid autoimmune seroreactions are slow processes.
Biosynthesis and regulation of iodolipids in calf thyroid
Authors: Chazenbalk G. D. , Pisarev M. A. , Juvenal G.J. , de Pisarev D. L. Kleiman , Mercuri H. , De Tomás M.
Published: December 2008

Abstract. The incorporation of 125I into iodolipids was investigated in calf thyroid slices. Time course studies showed that the iodination of lipid reaches a plateau after 30 min of incubation. A highly significant correlation was found between iodination of lipid and of protein (r = 0.906), suggesting that both reactions may be related. Addition of PTU or MMI caused a significant inhibition of lipid iodination, indicating that a peroxidase could be involved in this reaction. The iodinated lipids are not attached to protein, since they migrated in BEA chromatography and pancreatin digestion of the samples did not modify the percentage radioactivity. The iodolipid fraction observed in BEA chromatography was eluted and analysed by TLC. Iodinated free fatty acids and neutral lipids comprised most of the radioactivity. Although iodolipids are present in every subcellular fraction, the 20000 × g pellet had the greatest proportion of iodinated fatty acids and neutral lipids.

The iodination of lipids is under the control of both TSH and T3. These hormones caused a significant increase at 30–45 min of pulse labelling with 125I. Inhibition of prostaglandin synthesis with indomethacin caused a significant increase in lipid iodination. On the other hand, when phospholipase A2 was blocked by mepacrine, labelling of iodolipid was strongly decreased.
Bombesin inhibits thyrotrophin secretion in rats
Authors: Mitsuma Terunori , Nogimori Tsuyoshi , Chaya Masahiro
Published: December 2008

Abstract. The effects of peripheral administration of bombesin on thyrotrophin-releasing hormone (TRH) and thvrotrophin (TSH) secretion in rats were studied. Bombesin (200 μg/kg) was injected iv, and the rats were serially decapitated. TRH, TSH and thyroid hormone were measured by radioimmunoassay.

The hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after bombesin injection, whereas plasma concentrations tended to decrease, but not significantly. Plasma TSH levels decreased significantly in a dose-related manner with a nadir at 40 min after the injection. Plasma thyroid hormone levels did not change significantly. Plasma ir-TRH and TSH responses to cold were inhibited by bombesin, but the plasma TSH response to TRH was not affected. In the pimozide- or para-chlorophenylalanine pre-treated group, the inhibitory effect of bombesin on TSH levels was prevented, but not in the l-Dopa- or 5-hydroxytryptophan pre-treated group. These drugs alone had no effect on plasma TSH levels in terms of the dose used. The inactivation of TRH immunoreactivity in plasma or hypothalamus in vitro after bombesin injection did not differ from that of the controls.

These findings suggest that bombesin acts on the hypothalamus to inhibit TRH release, and that its effects are at least partially modified by amines of the central nervous system.
Reversal of insulin resistance in adipose tissue of non-insulin-dependent diabetics by treatment with diet and sulphonylurea
Authors: Bolinder Jan , Östman Jan , Arner Peter
Published: December 2008

Abstract. The effect of conventional treatment on insulin action in subcutaneous adipose tissue was studied in 6 patients with non-insulin-dependent diabetes mellitus (NIDDM). Insulin receptor binding and the effect of the hormone on glucose oxidation were determined before and after 6–14 months of treatment with diet plus sulphonylurea. Glycaemic control and in vivo insulin sensitivity were significantly improved by the treatment. Before treatment, the adipocyte insulin receptor binding and the sensitivity to insulin stimulation of adipose tissue glucose oxidation were normal and did not change after treatment. In contrast, the maximum insulin-induced glucose oxidation was markedly decreased before treatment, whereas it was totally normalized after treatment. The conclusion is that insulin resistance in adipose tissue of NIDDM subjects is solely due to post-receptor defects in insulin action. This resistance is completely off-set by conventional treatment with diet plus sulphonylurea.
Presence of salivary Protein C and salivary peptide P-C-like immunoreactivity in the laryngo-tracheo-bronchial glands
Authors: Ito Seiki , Suzuki Toshimitsu , Momotsu Takeshi , Isemura Satoko , Saitoh Eiichi , Sanada Kazuo , Shibata Akira
Published: December 2008

Abstract. An indirect immunofluorescence technique using antisera aganist salivary peptide P-C and against salivary Protein C was carried out on the laryngeal, tracheal and bronchial glands to examine whether salivary peptide P-C-like immunoreactivity, recently demonstrated in the serous cells of the human salivary glands, was also present in those of laryngeal, tracheal and bronchial glands and to ascertain whether salivary peptide P-C is a fragment of salivary Protein C or not. Salivary peptide P-C-like immunoreactivity was present in the serous cells of the human laryngeal, tracheal and bronchial glands. Observation of serial sections immunostained with two kinds of antisera revealed that cells reacting with antisera against salivary peptide P-C were identical to those reacting with antisera against salivary Protein C pre-incubated with salivary peptide P-C. The finding implied that salivary peptide P-C and salivary Protein C, originally isolated from human saliva, were also present in the serous cells of tissues other than the salivary glands. Furthermore, analysis of the primary structure of salivary peptide P-C and salivary Protein C together with the present morphological finding suggests that salivary peptide P-C is a COOH-terminal fragment of salivary Protein C. Thus, salivary Protein C and salivary peptide P-C may play some role in the function of the serous cells of the salivary and laryngo-tracheobronchial glands.
Suppressive effect of prolactin on oestrogen-induced secretion of LH by sequentially perifused rat hypothalamus-pituitary
Authors: Lee Jin-Woo , Miyake Akira , Tasaka Keiichi , Otsuka Shirou , Aono Toshihiro , Kurachi Keiichi
Published: December 2008

Abstract. The effect of prolactin (Prl) on oestrogeninduced gonadotrophin secretion was examined in vitro in a sequential double chamber perifusion system. As control groups, mediobasal hypothalamus (MBH)-pituitary pairs or pituitaries without the MBHs were perifused with Medium 199. As an experimental group, MBH-pituitary pairs were perifused with Medium 199 containing 1 μg/ml of rat Prl. These groups were stimulated with 10−7m oestradiol-17β (E2) for 30 min, and luteinizing hormone (LH) in the serial fractions of effluent was measured.

In the control group of MBH-pituitary pairs perifused with medium without Prl, secretion of LH began to rise within 30 min after the beginning of stimulation, reached a peak 30 min after the end of stimulation and then remained at a plateau for the rest of the experimental period, whereas in the control group of pituitaries alone no significant response was observed. In the experimental group perifused with medium containing Prl, LH-secretion showed peaks 20 and 80 min after the end of E2-stimulation, respectively, and the first peak was significantly (P < 0.01) less than the level in the control group.

These data demonstrate that Prl at this concentration suppressed the rapid LH release induced by E2. Its site of action is suggested to be at the hypothalamic level, and its possible mechanism of action is discussed.
Insulin-like growth factor I and growth hormone in canine starvation
Authors: Eigenmann J. Eugen , de Bruijne Jan. J. , Froesch E. Rudolf
Published: December 2008

Abstract. The roles of plasma insulin-like growth factor I (IGF I) and growth hormone (GH) were studied in 7 beagle dogs before and during starvation and during refeeding. IGF I levels significantly decreased from 75.2 ± 5.9 ng/ml at 7 days prior to the start of starvation to 9 ± 1.7 ng/ml at 19 days after the commencement of starvation (mean ± sem; P < 0.0001). During refeeding IGF I significantly rose from 9 ± 1.7 ng/ml to 55.5 ± 7.5 ng/ml within 9 days (mean ± sem; P < 0.002).

During starvation plasma GH levels significantly increased (P < 0.05) and these elevated levels returned to normal during refeeding. The dogs' GH secretory capacity significantly increased during starvation (P = 0.012) and became normal again during refeeding. The following conclusions can be drawn from this study: 1) starvation in the dog leads to a significant and drastic reduction of the circulating levels of IGF I, and 2) starvation in the dog, as in man, leads to increased circulating GH levels and to an increased GH-secretory capacity possibly brought about by a lack of a negative feedback normally exerted by IGF I.
Comparison of in vivo effects of insulin-like growth factors I and II and of growth hormone in hypophysectomized rats
Authors: Schoenle Eugen , Zapf Jürgen , Hauri Christina , Steiner Therese , Froesch E. R.
Published: December 2008

Abstract. Pure human IGFI (43 and 103 μg/day) and IGFII (131 μg/day) were infused into hypophysectomized rats during 6 days by means of sc implanted minipumps. Their effects on several growth indices were compared with those of various doses of sc infused human growth hormone. Growth hormone infusion produced a dose-dependent rise of endogenous rat IGF from 39 (without growth hormone) to 86 μU equivalents/ml (with 400 mU hGH/day) as determined by a competitive protein binding assay with a human IGF standard. In rats receiving the two doses of IGFI, total serum IGF levels rose to 83 and 99 μU equivalents/ml, respectively, in those receiving the IGFII dose the total serum IGF level rose to 146 μU equivalents/ml. These increases corresponded to steady state levels of 168 and 286 ng/ml of immunoreactive insulin-like growth factor (IR-IGF) I and 320 ng/ml of IR-IGFII. IGFI, but not IGFII led to an increase in body weight similar to that induced by the low doses of hGH (12.5 and 25 mU, respectively). The rise of endogenous rat IGF as well as the infused human IGFI and II caused a widening of the tibial epiphysis and an increase of the [3H]thymidine incorporation into costal cartilage. With respect to these two indices IGF II was clearly less potent that IGF I. When expressed in μU equivalents of the protein binding assay, endogenous rat IGF induced by hGH appeared to be relatively more effective than infused human IGF I or II.

Growth hormone infusion produced a change in the radiochromatographic [125I]IGF binding pattern of hypox rat serum: the gammaglobulin-sized specific IGF binding peak that is characteristic of normal rat serum but lacking in serum of hypophysectomized rats reappeared. Neither infused IGF I nor IGF II had this effect. It may be concluded that the infusion of human IGF I or II in hypophysectomized rats produced qualitatively the same effects on growth indices as a growth hormoneinduced increase of endogenous rat IGF. This supports the idea that IGF I and to some extent also IGF II are able to mediate some of the actions of growth hormone. Other growth hormone effects appear to depend on growth hormone directly.
Plasma concentrations of 1-deamino-8-d-arginine vasopressin after intragastric administration in the rat
Authors: Lundin Stefan , Melin Per , Vilhardt Hans
Published: December 2008

Abstract. A sensitive and specific radioimmunoassay for 1-deamino-8-d-arginine vasopressin (DDAVP) was developed. Plasma concentrations of DDAVP after intragastric administration were determined in non-fasted rats and a dose-related increase in plasma levels was obtained. The immunoidentity of plasma DDAVP and standard was established by high performance liquid chromatography (HPLC). Correlation of biological and immunological responses of DDAVP was assessed using the antidiuretic effect in the Brattleboro (diabetes insipidus) rat.
Different alterations of nuclear triiodothyronine receptor capacity in liver and kidney induced by starvation and triiodothyronine administration
Authors: Nakamura Hirotoshi , Yokota Toshihiko , Imura Hiroo
Published: December 2008

Abstract. Many studies have shown alterations in the number of nuclear triiodothyronine receptor (NT3R) under pathophysiologic situations. Most of these studies were performed on the rat liver and it is not known whether NT3R in different tissues exhibits an alteration similar to that in the liver.

We compared the change of nuclear receptor capacity for T3 in the liver and kidney during starvation and after T3 injection. Fasting for 72 h decreased maximal binding capacity (Cmax) in the rat liver receptor to 67% of the control, while it did not significantly change Cmax in the kidney. These changes in Cmax were parallel to those of nuclear protein concentrations in both tissues. Daily sc injection of T3 (20 μg/100 g body weight) for 3 days also caused the different alteration of Cmax in the liver and kidney. After T3, hepatic NT3R increased to 182% of the control, but renal NT3R increased only to 136%. Association constants were the same in all groups. These results show that changes of NT3R capacity under some conditions vary in different tissues.
Effects of insulin-like growth factors on chick embryo hepatocytes
Authors: Widmer U. , Schmid Ch. , Zapf J. , Froesch E. R.
Published: December 2008

Abstract. Biological effects of insulin-like growth factors (IGF) I and II on primary cultures of chick embryo liver cells have been investigated and compared 1) with the biological effect of insulin and 2) with competitive binding of the three hormones to their respective binding sites.

IGF I and II stimulate the incorporation of d[U-14C]-glucose into liver cell glycogen in a time- and dose-dependent manner, but with a 5–10-fold lower potency than insulin: Both IGFs also lead to enhanced incorporation of 5-[3H]uridine and l[U-14C]valine into trichloroacetic acid (TCA) insoluble material and to activation of ornithine decarboxylase activity. Their potency in stimulating RNA synthesis and ornithine decarboxylase activity is comparable to that of insulin. Protein synthesis is maximally stimulated at 3 nm by all three hormones. In the competitive binding studies, IGF I and II are 10-fold less potent than insulin in competing for [125I]insulin binding, but 100-fold more potent than insulin in competing for [125I]IGF I or II binding.

These studies show that IGF I and II stimulate the same metabolic indices as insulin in the chick embryo liver. By comparing these biological effects with competitive binding data it appears that IGFs act on glucose metabolism in the chick embryo liver via the insulin receptor, whereas stimulation of growth indices by IGFs and insulin appears to be mediated by their own specific receptors.
Effects of oestradiol and prolactin on progesterone production by rhesus monkey luteal cells in vitro
Authors: Laherty Richard F. , Rotten Daniel , Yamamoto May , Jaffe Robert B.
Published: December 2008

Abstract. The effects of oestradiol and prolactin (Prl) on progesterone production by dispersed monkey luteal cells were examined. Corpora lutea were recovered from monkeys 5–7 days following ovulation induction during the puerperium. The tissue was dispersed by collagenase and mechanical disruption. The resulting cells were incubated in Dulbecco's modified Eagle's medium, containing the hormones to be tested, for 3 h at 37°C. The medium was removed and assayed for progesterone by RIA. Human luteinizing hormone (hLH) produced a significant, dose-related increase in progesterone secretion that was comparable to that produced by dibutyryl cyclic adenosine monophosphate. Human follicle stimulating hormone (hFSH) had no effect upon progesterone production by the luteal cells. Oestradiol (100–10 000 pg/ml) produced a significant, dose-related decrease in both basal and hLH-stimulated progesterone production. Ovine Prl (oPrl) had neither a stimulatory nor an inhibitory effect upon basal progesterone secretion at doses up to 1000 ng/ml. Further, oPrl did not affect hLH-stimulated progesterone production. We conclude that oestradiol is a potent inhibitor of luteal progesterone secretion in vitro and that Prl does not inhibit progesterone production in the primate corpus luteum under these experimental conditions.
Absence of circulating desialylated thyroxine-binding globulin in patients with hepatobiliary disease
Authors: Costante Giuseppe , Sand Georges , Reding Pierre , Glinoer Daniel
Published: December 2008

Abstract. Thyroxine-binding globulin (TBG) is the major thyroid hormone carrier protein. The molecule contains approximately 10 sialic acid residues which play a key role in the peripheral metabolism of TBG. Since the serum of patients with liver disease often contains large amounts of several desialylated glycoproteins, the aim of the present studies was to characterize circulating TBG and to examine the possible presence of desialylated TBG (dTBG) in 24 patients with a variety of hepatobiliary diseases and selected on the basis of elevated serum levels of desialylated glycoproteins. Using 4 immunochemical techniques applied for the measurement of TBG, for the detection of dTBG and for the characterization of TBG microheterogeneity, the results indicated: a) a wide scatter of serum TBG levels between 4 and 23 mg/l; b) the absence of detectable amounts of dTBG in any of the sera tested; and c) a close similarity between the microheterogeneity of TBG in patients with liver disease with that of control sera or of purified TBG. In conclusion, in patients with acute and chronic liver disease, TBG, although quantitatively modified, remains qualitatively unaltered, suggesting that diseased liver produces fully sialylated TBG and that its catabolism is not impaired.
Physiological dosing of exogenous ACTH
Authors: Graybeal Michael L. , Fang Victor S.
Published: December 2008

Abstract. We evaluated the ACTH and cortisol responses to several doses of exogenous ACTH, and compared these values to the physiologic responses obtained in normal subjects undergoing insulin-induced hypoglycaemia. We determined that a cosyntrophin dose of 0.2 μg/kg body weight produced both ACTH and cortisol levels indistinguishable from the 'physiologic' stress-induced values. Since this dose is approximately 4 per cent of the standard 250 μg dose employed in tests of adrenal function, our findings suggest a need for caution in the interpretation of such tests.
Effects of experimentally-induced diabetes on oestradiol-stimulated changes in the ultrastructure of the rat endometrium
Authors: Frederick G. T. , Kirkland J. L. , Stancel G. M. , Gardner R. M.
Published: December 2008

Abstract. Alterations in endometrial cell morphology following oestradiol treatment of ovariectomized animals were examined in euglycaemic and streptozotocin-induced diabetic rats. Endometrial morphology was examined 18, 24, 36 and 48 h after oestradiol administration. Nuclei of endometrial cells from saline injected euglycaemic and diabetic rats exhibited pleomorphic nuclei with areas of heterochromatin dispersed throughout the nucleus. Nucleoli were homogenous in appearance and endometrial cells showed no mitotic chromosome function or cell division. The cytoplasm of euglycaemic and diabetic cells contained few mitochondria. The mitochondria that were present contained a uniformly dense matrix and cristae that extended across the mitochondria.

The formation of round to oval shaped nuclei with diffuse euchromatin was observed at 18, 24 and 36 h following oestradiol administration in euglycaemic animals. Alterations in nuclear morphology and the formation of euchromatin were absent or reduced at the same time intervals examined in diabetic animals. Nucleoli in oestradiol-treated euglycaemic animals at 18, 24 and 36 h post-injections became very prominent and displayed easily visible granules and fibrillar material. Comparable changes in nucleolar morphology in oestradiol-treated diabetic rats were absent.

The development of oval to round mitochondria containing short cristae and an electron-lucent matrix became apparent at 18 h post-injection of oestradiol in euglycaemic control animals. Alterations in mitochondrial morphology did not appear in endometrial cells of oestradioltreated diabetic animals at any of the time points examined. At 24 and 36 h post-injection of oestradiol in euglycaemic animals, mitotic figures were observed in mitochondrial cells. Cell division and mitotic figures were not observed in oestradiol-treated diabetic animals. This study demonstrates that a diabetic state in experimental animals profoundly alters the ability of oestradiol to stimulate normal endometrial cell growth.
The distribution of corticotrophin-releasing factor immunoreactivity in various ovine tissues
Authors: Kawai Koichi , Hotate Koichi , Chiba Yukinobu , Munekata Eisuke , Ohashi Shinichi , Wakabayashi Ichiji , Yamashita Kamejiro
Published: December 2008

Abstract. The presence of CRF in various ovine tissues has been quantified by a radioimmunoassay using an antibody raised against ovine CRF synthesized in vitro. Acetic acid extracts of ovine hypothalamus, cerebral cortex, cerebellum, pituitary and a number of visceral organs assayed in serial dilutions gave inhibition curves parallel to those of synthetic CRF. The highest concentration of CRF immunoreactivity (CRF-I) was found in the pituitary (84.6 ± 8.77 ng/g wet weight) and the second highest in the hypothalamus (79.1 ± 2.77 ng/g wet weight). CRF-I in the cerebral cortex and visceral organs (stomach, duodenum, jejunum, ileum, pancreas and liver) was about 60 and 30% of that in the hypothalamus, respectively. Chromatography of extracted CRF-I from these tissues on Bio-Gel P-10, equilibrated and eluted with 0.1 m acetic acid, revealed a single immunoreactive peak corresponding to synthetic ovine CRF. These findings indicate that CRF is generally distributed throughout ovine tissues including visceral organs, although its function remains to be clarified.
Correlation between the number of thyroliberin binding sites, the tumour size and the plasma prolactin level in human prolactin-secreting adenomas
Authors: Le Dafniet M. , Pagesy P. , Brandi A. M. , Racadot J. , Peillon F.
Published: December 2008

Abstract. Basal plasma prolactin (Prl) level, tumour size and [3H]thyroliberin (TRH) binding to tumour membranes were studied in 18 patients bearing Prl-secreting adenomas. Big tumours (grade III) were associated with high plasma Prl levels (median value: 1929 (range: 207–3570) ng/ml) and possessed numerous membrane TRH receptors (median value: 508 (range: 0–1200) fmol/mg of protein). By contrast, smaller tumours (grade II and I) were associated with lower plasma Prl levels (median values: 1085 (range: 40–1890) and 295 (range: 98–788) ng/ml, respectively) and possessed fewer membrane TRH receptors (median values 122 (range: 11–328) and 13 (range: 0–52) fmol/mg of protein, respectively). A direct positive correlation was demonstrated between the plasma Prl level and the number of [3H]TRH binding sites (ϱ: 0.729 P < 0.001). That the higher number of TRH receptors is associated with the largest tumours may be of importance in hyperprolactinaemia and should be taken in account when speculating on the pathogenesis of human Prl-secreting adenomas.
Plasma prolactin in the rat during suckling without prior separation from pups
Authors: Mattheij John A. M. , Swarts Hans J. M. , van Mourik Simone
Published: December 2008

Abstract. The relation between suckling and plasma prolactin (Prl) was studied in the rat, without prior separation of the dam from its pups. When the pups were replaced by a hungry foster litter, upon renewed suckling plasma Prl showed episodic increases and decreases in individual rats. When, subsequent to litter removal, similar rats were injected with perphenazine, a significant increase of plasma Prl was observed. This indicates that a decline of plasma Prl during suckling was not caused by exhaustion of Prl stores in the pituitary. In 22 individual rats blood was sampled every other minute while observations were made on nursing behaviour of the dams. During apparent suckling, increases as well as decreases of plasma Prl occurred. However, in most cases suckling did not affect plasma Prl, i.e. it remained stable at a high or a relatively low level. On the other hand, a considerable rise of plasma Prl was frequently observed when a dam was away from the nest. The data indicate that in the physiological situation Prl secretion from the pituitary is not directly related suckling activity, though episodes of suckling are essential to maintain a high Prl secretory capacity of the pituitary gland.
Age-related changes in prolactin and growth hormone release from pituitary glands in vitro
Authors: Hall T. R. , Harvey S. , Chadwick A.
Published: December 2008

Abstract. The basal release of prolactin from cockerel anterior pituitary glands in vitro declined between 1 and 7 weeks of age, to a level less than that released by pituitary glands from 18 week old (adult) cockerels and hens. Basal growth hormone (GH) release increased between 1 and 7 weeks of age but had declined in adults to a level similar to that released from 4 weeks old cockerels. The responsiveness of the pituitary gland to hypothalamic stimulation, using hypothalami from 8 week old broiler fowl, was also age-related. Prolactin release was considerably higher from pituitaries of 1 week old cockerels compared to the other age groups. Stimulation of GH release by the hypothalamus was higher from pituitaries of both 1 and 7 week old cockerels compared to the other groups of birds. The increase in release of prolactin following incubation with thyrotrophin releasing hormone (TRH) declined between 1 and 7 weeks, but increased slightly in adult birds, whereas the increase in release of GH following TRH was higher from pituitaries of both 1 and 7 week old cockerels. Hypothalamic prolactin (Prl) releasing activity, measured as the ability of the hypothalamus to stimulate hormone release from 8 week old broiler fowl anterior pituitary glands, declined with the age of the donor cockerels. The hypothalami from adult hens secreted significantly more Prl releasing activity than did adult cockerel hypothalami. The secretion of GH releasing activity decreased markedly with the age of the donor bird.

These results suggest that maturational patterns of hormone secretion in fowl are partly due to changes in autonomous hormone release, to changing patterns of hypothalamic activity and to differences in pituitary responsiveness to provocative stimuli.
Triiodothyronine binding immunoglobulin in a euthyroid man without apparent thyroid disease; its properties and effects on triiodothyronine metabolism
Authors: Isozaki Osamu , Tsushima Toshio , Sato Kanji , Saji Motoyasu , Ohba Yoshito , Emoto Naoya , Sato Yuji , Shizume Kauzo
Published: December 2008

Abstract. A 54 year old man with markedly elevated serum T3, but without an apparent thyroid disease, was found to have a specific antibody to T3. His serum thyroxine, TBG and TSH were in normal range, but T3-RSU was markedly low. Antibodies to thyroglobulin and microsome were negative. He was judged euthyroid because of a normal basal metabolic rate and a normal thyroidal 123I uptake which was suppressed by T3 adminnistration. When serum was extracted with ethanol prior to assay, serum T3 was found to be in the upper border of normal range. Several experiments revealed the presence of an antibody to T3 in his serum with an affinity constant of 3.3 × 109m−1. The binding capacity of the antibody was 7.6 ng/mg of IgG. The binding of [125I]T3 was almost specific to T3, and potencies of T4 and fT3 in displacing [125I]T3 binding were only 1.0 and 0.3%, respectively, of that of T3. The antibody contained both kappa and lambda chains and was therefore polyclonal.

The T3 metabolic clearance rate, which was determined by disappearance of injected [125I]T3 from serum, was lower in this patient (7.44 I/day) than in normal. The T3-production rate was decreased to 14.9 μg/day, and serum free T3 concentration as well as urinary T3 excretion rate were also reduced. Since both serum total and free T4 concentrations were normal, the supply of T4 to peripheral tissues would be sufficient to keep this patient in a euthyroid state in spite of the anti-T3 antibody.
Immunoreactive neurotensin in spontaneous syndromes of obesity and diabetes in mice
Authors: Sheppard Michael C. , Bailey Clifford J. , Flatt Peter R. , Swanston-Flatt Sara K. , Shennan Kathleen I.J.
Published: December 2008

Abstract. Immunoreactive neurotensin was measured in plasma and acid-ethanol extracts of brain, intestine and pancreas of obese hyperglycaemic (ob/ob) mice of the Aston strain, C57BL/KsJ diabetes-obese (db/db) mice, and their respective lean controls. In lean mice, the intestine was the major source of neurotensin (156–194 ng/g wet weight and 169–361 ng/intestine), with smaller amounts in the brain (33–43 ng/g and 13–17 ng/brain), pancreas (0.8–1.1 ng/g and 0.28–0.32 ng/pancreas) and plasma (50–100 pg/ml). Compared with lean controls, ob/ob and db/db mice exhibited 13 and 23% decreases in brain weight, and 37 and 82% increases in intestinal weight. Concentrations of neurotensin in plasma and brain were similar in lean and obese-diabetic mutant mice, but the total content of brain neurotensin was 25% lower in ob/ob mice. Neurotensin was unchanged in the pancreas of db/db mice. However, raised concentrations and total contents of neurotensin were observed in the pancreas of ob/ob mice (72 and 57%, respectively) and the intestine of both ob/ob (56 and 118%) and db/db (35 and 144%) mice. These observations raise the possibility that increased neurotensin concentrations might exert local effects in the intestine and pancreas which contribute to the pathogenesis of obesity-diabetes syndromes in mice.
Renin and angiotensins in cultured mouse adrenocortical tumour cells
Authors: Naruse Mitsuhide , Shizume Kazuo , Inagami Tadashi
Published: December 2008

Abstract. Mouse adrenal tissue has been reported to contain high renin activity. However, it is not clear whether the renin is produced inside the tissue or is derived from a blood-borne component. We have investigated a cloned cell line of mouse adrenocortical tumour (Y-1) which has a steroidogenic activity. Sizable quantities of renin were demonstrated, predominantly in the cell lysate. This renin activity was distinguished from cathepsin D in view of its specific affinity to anti-renin antibody, optimal pH was determined, and the substrate specificity was checked with haemoglobin. Immunoreactive angiotensins were also detectable, but were demonstrated both in the cell and in the culture medium. This study provides further evidence for the existence of renin intrinsic to the adrenal gland. This study also suggests an intracellular role for renin and possible secretion of generated angiotensins.
Steroidogenesis in isolated rat granulosa cells – changes during follicular maturation
Authors: Nordenström Knut , Johanson Carl
Published: December 2008

Abstract. Steroid release was investigated in granulosa cells isolated from rat ovarian follicles at different maturation stages. Immature rats were treated with 10 IU of pregnant mare's serum gonadotrophin (PMSG) to induce follicular growth and maturation. Granulosa cells were isolated and subsequently incubated for 4 h in the absence or presence of follicle stimulating hormone (FSH), luteinizing hormone (LH) or forskolin. The concentrations of progesterone (P), 20α-dihydroprogesterone (20αDHP), testosterone (T) and oestradiol (E2) in the media were determined by radioimmunoassay. During maturation, basal release of T increased markedly at late dioestrus. At pro-oestrus, concomitant with a sharp rise in E2 and P release, T release returned to previously low levels. Addition of FSH or LH stimulated P release at late dioestrus and pro-oestrus but had no effect on E2 or T levels. Basal 20αDHP levels remained low until a sharp rise at mid pro-oestrus. A stimulatory effect of gonadotrophins on 20αDHP was first seen at this stage. The adenylate cyclase stimulator forskolin resembled FSH in all its effects.

In summary, the present study demonstrates that maturing, but not preovulatory, granulosa cells have an increased capacity to release T during a relatively short period. It is suggested that this T peak could be of great importance for the further progress of follicular maturation.
Decreased responsiveness to chronic salmon calcitonin treatment in rat kidney and calvaria studied using quantitative enzyme cytochemistry
Authors: Salmon D. Michael , Azria M. , Zanelli Joan M.
Published: December 2008

Abstract. Growing rats were treated with daily im doses of salmon calcitonin (sCT) (2, 15 and 100 IU/kg) for various times (1, 4 and 24 weeks). The effects on intracellular enzyme activities in bone and kidney were monitored using quantitative cytochemical methods previously developed for the identification of specific target tissue responses to calcitonins. The basal alkaline phosphatase activities in both kidney and bone were decreased by long-term treatment at all time periods and doses tested. No change was noted in basal Ca ATPase activities in kidney after treatment. The capacity of target tissues in chronically treated and control rats to respond to an acute iv dose of sCT was also compared. Acute provocation tests in treated and control rats showed that the renal alkaline phosphatase response was decreased in the rats receiving long-term treatment. Moreover, the direction of response was reversed in chronically treated rats when bone alkaline phosphatase and renal Ca-dependent ATPase activity was measured after acute provocation with sCT, i.e. bone alkaline phosphatase was stimulated instead of being inhibited and renal Ca ATPase was inhibited instead of being stimulated. The application of quantitative cytochemial techiques has demonstrated intracellular changes in enzyme activites in both kidney and bone. The impaired sCT responsiveness can be detected at shorter times of treatment (1 week) and lower doses (2 IU/kg) than has previously been possible by measurement of indices of mineral metabolism in plasma or urine.
Effects of thyrotrophin-releasing hormone on plasma catecholamine levels in acromegalics
Authors: Rozenberg Isabelle , Manchon Philippe , Sabetier Catherine , Hazard Jean , Lhoste François
Published: December 2008

Abstract. Plasma catecholamines assayed by a double isotope radio enzymatic method were studied in the basal state and during a thyrotrophin-releasing hormone (TRH)-test in 7 acromegalics, divided into 2 groups: active and non-active acromegalics, according to clinical and biological criteria. Basal plasma norepinephrine levels were significantly increased in the active group 648 ± 22 pg/ml (P < 0.001) and were in the normal range in the non-active group 439 ± 26 pg/ml. Basal plasma epinephrine values were not significantly different in the 2 groups 59 ± 15 pg/ml vs 34 ± 7 pg/ml. During a TRH-test, norepinephrine levels remained elevated (P < 0.001) in the active group, and the difference between the 2 groups was enhanced during the test. On the other hand the 2 patients who responded to TRH demonstrated an increase of norepinephrine levels. Our results suggest that TRH may stimulate norepinephrine release in acromegalics with an active response to TRH.