bluuebunny/crossref_metadata_2025_split huggingface dataset:
Action of opioid peptides on the rat adrenal cortex: stimulation of steroid secretion through a specific μ opioid receptor
Authors: Kapas S , Purbrick A , Hinson J P 
Published: December 2008

Abstract
While there have been several studies on the actions of opioid peptides on adrenocortical steroidogenesis, the results of these studies have failed to resolve the question as to whether these peptides exert a direct action on the adrenal cortex. The present studies were designed to address this question directly, using collagenase-dispersed rat zona glomerulosa and zonae fasciculata/reticularis cells incubated in vitro. The results obtained clearly show that the opioid peptides tested (β-endorphin, Leu-enkephalin, Met-enkephalin, and its long-acting analogue, DALA) all exerted a significant stimulatory effect on aldosterone secretion by zona glomerulosa cells and all, except Leuenkephalin, stimulated corticosterone secretion by inner zone cells. The response was shown to be inhibited by naloxone. There did not appear to be a significant interaction between the effects of ACTH and the opioid peptides on adrenocortical cells.
Studies using specific agonists for opioid receptor subtypes (DAMGO, DPDPE and U-50488H, specific for μ, δ and κ receptors respectively) showed that the effect of opioid peptides on the zona glomerulosa appeared to be mediated exclusively by μ receptors while the response of inner zone cells was mediated by both μ and, to a lesser extent, κ receptors. Finally, studies on the second messenger systems activated by the opioid peptides and the receptor agonists showed that these peptides act to increase labelling of inositol trisphosphate, and strongly suggest that, in the rat adrenal cortex, both μ and κ opioid receptors are linked to the activation of phospholipase C.
Journal of Endocrinology (1995) 144, 503–510
IGF binding proteins-4, -5 and -6 may play specialized roles during L6 myoblast proliferation and differentiation
Authors: Ewton D Z , Florini J R 
Published: December 2008

Abstract
It is well known that IGFs-I and -II stimulate both the proliferation and differentiation of myoblasts, but the role of the IGF binding proteins (IGFBPs) during these processes has not been established. In this study we show that IGF-I analogs with greatly reduced affinity for IGFBPs exhibited about a 10-fold increase in potency in stimulating proliferation (as in other cell types), but up to a 100-fold greater potency than native IGF-I in stimulating L6A1c differentiation. Analysis of conditioned media revealed that L6 cells secrete significant levels of IGFBPs that react with antisera to IGFBP-4, -5 and -6. Steady-state levels of IGFBP-4 mRNA were highest in proliferating myoblasts, while IGFBP-5 mRNA could not be detected in myoblasts although its levels were dramatically increased during IGF- or insulin-stimulated differentiation of myoblasts into myotubes. Elevated IGFBP-6 mRNA levels were found in quiescent cells in serum-free medium. IGF-I and IGF-II treatment elevated IGFBP-5 in conditioned media, but longR3IGF-I and insulin, which do not bind to IGFBPs, had smaller effects. This complex regulation of expression of different IGFBPs not only during different stages of muscle growth and differentiation, but also upon stimulation by IGFs or insulin, suggests that the IGFBPs play a specific and significant role in modulating the actions of the IGFs during myogenesis.
Journal of Endocrinology (1995) 144, 539–553
The effect of diabetes mellitus on urinary calcium excretion in pregnant rats and their offspring
Authors: Birdsey T J , Husain S M , Garland H O , Sibley C P 
Published: December 2008

Abstract
The effect of maternal diabetes mellitus on renal calcium excretion in pregnant rats and their offspring has been examined in order to ascertain the role of the kidney in the disturbed calcium homeostasis of infants born to diabetic mothers. Diabetic pregnant (DP) rats exhibited severe hypercalciuria which greatly exceeded the urinary calcium losses (UCaV) in non-diabetic pregnant (CP) or non-pregnant diabetic (D) rats. Means ± s.e.m. for UCaV at day 21 (mmol/24 h) were: DP=1·12± 0·09 (n=7); CP=0·06±0·01 (n=7); D=0·63±0·06 (n=7) (P<0·001 DP vs CP and DP vs D). The profile for urinary calcium excretion in the three groups was different from that of other measured ions. The degree of natriuresis, for example, was comparable in DP and D rats at all stages studied. Although magnesium output was significantly greater in DP than D rats on days 14 and 21, this appeared to result from an additive effect of the magnesiuresis seen when pregnancy and diabetes were studied separately.
The marked renal calcium wasting of diabetic pregnancy will have implications for overall calcium balance in the mother. For example, an enhanced intestinal calcium absorption was seen in DP rats in the second half of gestation. Means ± s.e.m. for day 21 (mmol/24 h) were: DP=3·8±0·8 (n=7); CP=1·4±0·3 (n=7); D=1·6±0·3 (n=7) (P<0·05 DP vs CP and DP vs D). The hypercalciuria may also contribute to the disturbed calcium homeostasis of the neonate if it reduces the amount of calcium available for transfer to the fetus.
In contrast to their mothers, the offspring of DP rats did not show a raised UCaV compared with CP pups. Means ± s.e.m. at day 1 postpartum (nmol/2 h per pup) were: DP=47·2±15·7 (n=4 litters); CP=72·2±14·1 (n=7 litters) (not significant). Changes in neonatal renal function are therefore unlikely to contribute to their disturbed calcium balance. In fact, their slightly reduced urinary calcium output may be an attempt to compensate for their lowered total body calcium as reported elsewhere.
Journal of Endocrinology (1995) 145, 11–18
Divergent regulation of rat adipocyte GLUT1 and GLUT4 glucose transporters by GH
Authors: Kilgour E , Baldwin S A , Flint D J 
Published: December 2008

Abstract
The effect of GH, in vivo, on the glucose transport systems of rat adipocytes has been investigated. Lowering of serum GH levels, by treatment of rats with an antiserum specific for rat GH (anti-rGH), significantly decreased serum levels of both IGF-I and insulin. Treatment with anti-rGH also increased glucose oxidation and the conversion of glucose to lipid by isolated adipocytes. Adipocyte glucose oxidation and lipid synthesis were measured in the presence of a limiting concentration of glucose and therefore reflect changes in glucose transport. Immunoblot analysis of adipocyte subcellular fractions revealed that anti-rGH induced an increase in the amount of the glucose transporters GLUT1 (1·6-fold) and GLUT4 (2·5-fold) present in plasma membranes and a decrease (39%) in the amount of GLUT4 present in low-density microsomal fractions. Lowering of serum GH also increased, by 36%, the amount of GLUT1 present in a total membrane fraction but had no such effect on GLUT4 levels. Replenishment of serum GH, by concurrent administration of ovine GH to rats, prevented all of these effects of anti-rGH. It was concluded that GH in vivo down-regulates the amount of both GLUT1 and GLUT4 present in rat adipocyte plasma membranes. This reflects a decrease in the total cellular levels of GLUT1 and modification of the subcellular distribution of GLUT4 and results in restriction of adipocyte glucose uptake.
Journal of Endocrinology (1995) 145, 27–33
Regulation of the TRH-like peptide pyroglutamyl-glutamyl-prolineamide in the rat anterior pituitary gland
Authors: Rondeel J M M , Klootwijk W , Linkels E , van Haasteren G A C , de Greef W J , Visser T J 
Published: December 2008

Abstract
TRH-like peptides share the N- and C-terminal amino acids with TRH (pGlu-His-Pro-NH2) but differ in the middle amino acid residue. One of them, pGlu-Glu-Pro-NH2 (<EEP-NH2; EEP) is present in the rat pituitary gland, but its biological significance is unknown. We investigated the localization and regulation of this tripeptide in the rat pituitary gland. To distinguish between TRH and EEP two antisera were used for RIA: specificity of antiserum 4319 for the TRH-like peptides pGlu-Phe-Pro-NH2 and EEP was equal to or greater than that for TRH, whereas antiserum 8880 is TRH-specific. Our RIA data showed the presence of a TRH-like peptide in the anterior pituitary gland (AP) and of TRH in the posterior pituitary gland (PP). The TRH-like peptide in the AP was identified on anion-exchange chromatography and subsequent HPLC as EEP. Pathophysiological conditions such as altered thyroid and adrenal status and suckling did not affect pituitary gland levels of EEP. In general, however, there is a clear sex difference: levels of EEP are higher in male than in female rats. In both sexes gonadectomy leads to a substantial two- to threefold rise in EEP levels, abolishing the sex difference. Testosterone administration to gonadectomized male rats normalizes levels of EEP again. Disulfiram, an inhibitor of the enzyme peptidylglycine α-amidating monooxygenase, reduced levels of EEP in the AP by approximately 50%. In conclusion: 1) the TRH-like peptide EEP is present in the AP, whereas TRH is confined to the PP, 2) levels of EEP in the AP are regulated by sex steroids, 3) EEP is actively amidated in the AP and thus seems to be produced from a glycine-extended progenitor sequence.
Journal of Endocrinology (1995) 145, 43–49
Ovine placental lactogen lacks direct somatogenic and anticatabolic actions in the postnatal lamb
Authors: Ogawa E , Breier B H , Bauer M K , Gluckman P D 
Published: December 2008

Abstract
The metabolic effects of ovine placental lactogen (oPL) alone and in combination with bovine GH (bGH) were investigated in comparison with the identical dose of bGH alone in the well-fed postnatal lamb. The animals were treated by twice daily intramuscular injection for 5 days with oPL (n=7), bGH (n=7) or bGH+oPL (n=7) at a dose of 0·3 mg/kg per day or saline (n=9). bGH and bGH+oPL treatments, but not oPL treatment, resulted in significantly (P<0·01) higher plasma IGF-I levels than saline treatment. The rate of net protein catabolism (NPC) was significantly (P<0·05) reduced to the same extent by bGH and bGH+oPL treatment compared with saline treatment. In contrast, oPL did not affect the rate of NPC. Blood glucose and insulin:glucose ratio were significantly (P<0·05) elevated in the bGH+oPL group, whereas they were not significantly altered by either bGH or oPL treatment. These results suggest that oPL alone is not somatogenic or anticatabolic in the postnatal lamb despite the earlier evidence that oPL can bind to the oGH receptor (oGHR). However, oPL appeared to augment some of the effects of bGH when administered together, particularly with respect to carbohydrate metabolism. Potentiation of the diabetogenic effect of bGH by oPL may lead to insulin resistance during pregnancy. The lack of any obvious actions by oPL treatment alone may support the hypothesis that oGHR homo-dimerization is required for the full activation of GHR-mediated effects, since oPL binding does not initiate homo-dimerization of the oGHR.
Journal of Endocrinology (1995) 145, 87–95
Starvation-induced changes in the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA and the hypothalamic release of proTRH-derived peptides: role of the adrenal gland
Authors: van Haasteren G A C , Linkels E , Klootwijk W , van Toor H , Rondeel J M M , Themmen A P N , de Jong F H , Valentijn K , Vaudry H , Bauer K , Visser T J , de Greef W J 
Published: December 2008

Abstract
The purpose of this study was to investigate the mechanisms involved in the reduced thyroid function in starved, young female rats. Food deprivation for 3 days reduced the hypothalamic content of prothyrotrophin-releasing hormone (proTRH) mRNA, the amount of proTRH-derived peptides (TRH and proTRH160–169) in the paraventricular nucleus, the release of proTRH-derived peptides into hypophysial portal blood and the pituitary levels of TSHβ mRNA. Plasma TSH was either not affected or slightly reduced by starvation, but food deprivation induced marked increases in plasma corticosterone and decreases in plasma thyroid hormones. Refeeding after starvation normalized these parameters. Since the molar ratio of TRH and proTRH160–169 in hypophysial portal blood was not affected by food deprivation, it seems unlikely that proTRH processing is altered by starvation. The median eminence content of pGlu-His-Pro-Gly (TRH-Gly, a presumed immediate precursor of TRH), proTRH160–169 or TRH were not affected by food deprivation. Since median eminence TRH-Gly levels were very low compared with other proTRH-derived peptides it is unlikely that α-amidation is a rate-limiting step in hypothalamic TRH synthesis.
Possible negative effects of the increased corticosterone levels during starvation on proTRH and TSH synthesis were studied in adrenalectomized rats which were treated with corticosterone in their drinking water (0·2 mg/ml). In this way, the starvation-induced increase in plasma corticosterone could be prevented. Although plasma levels of thyroid hormones remained reduced, food deprivation no longer had negative effects on hypothalamic proTRH mRNA, pituitary TSHβ mRNA and plasma TSH in starved adrenalectomized rats. Thus, high levels of corticosteroids seem to exert negative effects on the synthesis and release of proTRH and TSH. This conclusion is corroborated by the observation that TRH release into hypophysial portal blood became reduced after administration of the synthetic glucocorticosteroid dexamethasone.
On the basis of these results, it is suggested that the reduced thyroid function during starvation is due to a reduced synthesis and release of TRH and TSH. Furthermore, the reduced TRH and TSH synthesis during food deprivation are probably caused by the starvation-induced enhanced adrenal secretion of corticosterone.
Journal of Endocrinology (1995) 145, 143–153
Effect of glycoprotein and protein hormones on human meningioma cell proliferation in vitro
Authors: Boyle-Walsh E , Shenkin A , White M C , Fraser W D 
Published: December 2008

Abstract
Speculation that meningiomas are subject to female hormone influence is supported by their higher incidence in women and reports of exacerbation of symptoms during pregnancy and the luteal phase of the menstrual cycle. Previous reports have concentrated on the effects of the steroid hormones oestradiol and progesterone on meningioma proliferation. In this study we have investigated the roles of the glycoproteins LH, FSH and human chorionic gonadotrophin (hCG), and the protein hormones prolactin (PRL) and human placental lactogen (hPL) on the proliferation of human meningiomas in vitro. The three glycoproteins had an inhibitory effect on meningioma proliferation ranging from 5·0–50·0%, 10·0–63·0% and 2·4–34·0% at the highest concentrations of LH (25 mIU/ml), FSH (15 mIU/ml) and hCG (30 IU/ml) respectively. Cultures were also treated with PRL (100 and 200 ng/ml) and hPL (5 and 10 ng/ml) and the protein hormones had a stimulatory effect on cell proliferation of 12·0–55·5% and 11·4–73·6% when treated with 200 ng/ml PRL and 10 μg/ml hPL respectively. Our data suggest that increasing levels of the protein hormones PRL and hPL, falling levels of hCG and the absence of LH and FSH in the second and third trimesters of pregnancy may play a role in the acceleration of meningioma growth in these stages of pregnancy.
Journal of Endocrinology (1995) 145, 155–161
Vasopressin-stimulated insulin secretion and inositol phosphate production: interactions with glucose and phorbol esters
Authors: Richardson S B , Laya T , VanOoy M 
Published: December 2008

Abstract
Arginine vasopressin (VP) activates phospholipase C (PLC) and stimulates insulin secretion and inositol phosphate (insP) production in mouse islets and clonal hamster beta cells (HIT). The insulin response to VP is reportedly dependent on extracellular glucose and there is evidence that glucose also activates PLC. The interactions of VP and glucose have been further examined in HIT cells. Glucose stimulated insulin secretion but not insP production and VP stimulated both insulin secretion and insP production in the absence of extracellular glucose. However, in the presence of glucose the insulin and insP responses to VP were potentiated. The phorbol ester, tetradecanoylphorbol acetate (TPA), which activates protein kinase C (PKC), stimulated basal insulin secretion but inhibited insP production. In the presence of submaximal concentrations of VP, 100 nmol/l TPA inhibited VP-stimulated inositol monophosphate production and there was no additivity of stimulated insulin secretion. With a maximal (10 nmol/l) concentration of VP, TPA caused additive insulin secretion and insP levels were stimulated above baseline. Twenty-four hour preincubation with TPA to down-regulate PKC did not inhibit the insulin response to VP. We conclude that extracellular glucose does not activate PLC and is not required for VP-stimulated insulin secretion although it potentiates VP-stimulated insulin secretion and insP production.
Journal of Endocrinology (1995) 145, 221–226
Opioids modify the release of LH at the pituitary level: in vitro studies with entire rat pituitaries
Authors: Dragatsis I , Papazafiri P , Zioudrou C , Gerozissis K 
Published: December 2008

Abstract
It is currently accepted that opioids modify the secretion of LH by affecting the release of GnRH in the hypothalamus. A direct action of opioids at the pituitary level is not yet fully established. To this end, we tested the effects of opioids on the release of LH by the entire pituitary in adult male rats. Opioid agonists with mu (DAGO), delta (DSLET) and kappa (U-50488H) specificity were tested at 0·01 to 10 μm in static incubations. DAGO inhibited dose-dependently the spontaneous and GnRH-induced release of LH. DSLET inhibited only the GnRH-induced release of LH. On the other hand, U-50488H increased spontaneous LH release dose-dependently. The opioid antagonists naloxone, diallyl-G (delta antagonist) and MR 2266 (kappa antagonist) blocked the effects induced by DAGO, DSLET or U-50488H respectively, implying an opioid receptor-mediated effect. The above results showed that opioids with mu, delta and kappa specificity act on the entire pituitary and modify differentially the release of LH. In this study we also compared spontaneous and GnRH-induced LH release by anterior and entire pituitaries and found that the amount of LH released by the anterior lobe was twofold higher, suggesting that inhibitory factors present in the neurointermediate part may affect the release of LH.
Journal of Endocrinology (1995) 145, 263–270
3,5-Di-iodo-l-thyronine suppresses TSH in rats in vivo and in rat pituitary fragments in vitro
Authors: Horst C , Harneit A , Seitz H J , Rokos H 
Published: December 2008

Abstract
3,5-Di-iodo-l-thyronine (T2) is a naturally occurring metabolite of thyroxine (T4). Contrary to earlier findings, T2 has recently been shown to have rapid effects in rat liver and in mononuclear blood cells. In the experiments described here, T2 was tested to determine whether it has a TSH suppressive effect in rats in vivo and in rat pituitary fragments in vitro.
In experiments over 2 weeks in rats in vivo, low doses of T2 (20–200 μg/100 g body weight per day) had no significant influence on body and organ weights, but significantly decreased TSH and T4 serum concentrations. At 200 μg/100 g per day, T2 suppressed TSH to 43% and T4 to 29% of control levels. At 1–15 μg/100 g per day, 3,5,3′-tri-iodo-l-thyronine (T3), used as a comparison to T2, had significant effects on TSH and T4 levels, and also on body weight. Fifteen μg T3/100 g per day decreased TSH to 44%, T4 to 25%, and body weight to 59% of control levels.
In experiments over 3 months in rats in vivo, a low dose (25 μg/100 g per day) of T2 suppressed TSH to 60% and T4 to 57% of control levels and had no significant influence on other parameters. Conversely, 0·1 μg/100 g per day T3 had significant effects on body and organ weights as well as pellet intake, but a less pronounced TSH suppressive effect: TSH concentrations were unchanged and T4 concentrations were down to 80% of control values.
In rat pituitary fragments in vitro, a clear suppression of TSH secretion after a TRH pulse was demonstrated.
To summarise, T2 is a specific agonist in the negative feedback mechanism on TSH secretion at the pituitary level without other apparent thyromimetic effects.
Journal of Endocrinology (1995) 145, 291–297
Ontogeny of the GH response to phorbol ester and phospholipase C in rat pituitary cells
Authors: Cuttler L , Collins B J , Szabo M 
Published: December 2008

Abstract
GH secretory patterns undergo marked change during early mammalian development. The factors that underlie these changes and the major components of signal transduction in the immature somatotrophs are not fully understood. Increasing evidence suggests that protein kinase C (PKC) plays a central role in perinatal organ differentiation and function. To evaluate the possible role of PKC as a mediator of GH secretion from immature pituitaries, we tested the effects of the PKC activating phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA), alone or together with GH-releasing factor (GRF), somatostatin (SRIF), and Ca2+ modifying agents; an inactive phorbol analogue (4α-12–13-didecanoate; 4α-PDD), and phospholipase C on GH release from pituitary cell cultures from perinatal and mature rats.
Pituitary primary cell cultures were prepared from fetal (day 20 of 21·5 days of gestation), 2-day-old, 12-day-old, and adult male (2- to 4-month-old) rats. Each experiment was performed on at least three separate occasions. The magnitude of TPA (0·15–150 nm)-induced GH release was markedly age-dependent, fractional GH release being greatest from pituitaries of fetal and newborn rats, and least from those of adults (P<0·001). Further, the minimum dose of TPA required to stimulate GH release over basal levels was tenfold higher for adult pituitaries (15 nm) than for perinatal pituitaries (1·5 nm). Phospholipase C (1 and 10 U/ml) also caused greater fractional GH release from neonatal pituitaries than from adult pituitaries (P<0·01). By contrast, the inactive phorbol ester 4αPDD did not stimulate GH release from pituitary cells of 2-day-old, 12-day-old or adult rats.
SRIF (0·1–10 nm) inhibited TPA (150 nm)-induced GH release in a dose-dependent manner, but the degree of inhibition was significantly less in perinatal than in mature pituitaries (P<0·001). Combined treatment with near maximal stimulatory doses of GRF (1 nm) and TPA (150 nm) resulted in a partially additive GH response. Inhibitors of Ca2+ mobilization reduced TPA-induced GH release in all age groups, although GH suppression was least in pituitaries of immature rats.
These findings indicate that PKC activators such as TPA and phospholipase C are potent secretagogues of GH in perinatal pituitaries. The action of phorbol ester was mediated by Ca2+-dependent pathways in both immature and mature pituitaries. Somatotroph responsiveness to TPA and phospholipase C was strikingly age-dependent, with greatest GH response in the perinatal period and declining response with advancing age after birth. These data suggest that immature somatotrophs possess functional PKC-dependent signal transduction pathways whose relative contribution declines during postnatal development.
Journal of Endocrinology (1995) 145, 307–314