Inhibition in the rat of gastric acid secretion and cyclic AMP analogs accumulation in vitro by somatostatin.

Various somatostatin (S) analogs exhibited similar degree and similar, or shorter, duration of inhibition of basal gastric acid secretion as S in the unanesthetized rat and similar, or less, inhibition of the cyclic AMP accumulation induced by prostaglandin E2 in the rat anterior pituitary in vitro. With the analogs examined, the gastrointestinal and pituitary receptors appear to exhibit generally similar recognition specificity with the differences within the gastro-intestinal activities reflecting duration of availability rather than receptor affinity.     

Synthetic corticoliberin needs arginine vasopressin for full corticotropin releasing activity

Summary The corticotropin-releasing activity of synthetic corticoliberin increases 75–90% when it is incubated in the presence of arginine vasopressin with rat anterior pituitary cell suspensions; this suggests a synergistic control of ACTH secretion by vasopressin and corticoliberin.Acknowledgments. This study was supported by grant No. 3.581-0.79 of the Swiss National Science Foundation. We thank Ms C. Estoppey for technical assistance. Reprint requests should be addressed to A. B.     

Role of bombesin-related peptides in the mediation or integration of the stress response

In addition to the relatively well established role of corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) in the mediation of the stress response, there is reason to believe that bombesin-like peptides (BN-LPs) may also contribute to the mediation or integration of these responses and thus might be considered as putative 'stress peptides'. This review provides evidence supporting this contention by showing that (i) BN-LPs are present at brain sites known to be activated by stressors, (ii) stressor exposure alters utilization of BN-related peptides, (iii) exogenous BN administration mimics the endocrine, autonomic and/or behavioral effects elicited by stressors, and (iv) antagonism of BN action attenuates the behavioral and/or neurochemical effects of stressors or of exogenously administered peptide. The evidence presented also suggests that BN-LPs mediate their stress-relevant effects through activation of CRH and/or AVP neurons. Several hypothetical mechanisms for such peptidergic interactions are discussed as to the implications of considering BN-LPs as 'stress peptides'. Received 16 July 2001; received after revision 27 August 2001; accepted 28 August 2001     

Inhibition in the rat of gastric acid secretion and cyclic AMP analogs accumulation in vitro by somatostatin

Summary Various somatostatin (S) analogs exhibited similar degree and similar, or shorter, duration of inhibition of basal gastric acid secretion as S in the unanesthetized rat and similar, or less, inhibition of the cyclic AMP accumulation induced by prostaglandin E₂ in the rat anterior pituitary in vitro. With the analogs examined, the gastrointestinal and pituitary receptors appear to exhibit generally similar recognition specificity with the differences within the gastrointestinal activities reflecting duration of availability rather than receptor affinity.The author acknowledges the technical assistance of Mr L. Chamberland, Miss A. Colaviti and Miss C. Pilapil.     

Mitochondria as the conductor of metabolic signals for insulin exocytosis in pancreatic beta-cells

Mitochondrial metabolism is crucial for the coupling of glucose recognition to the exocytosis of the insulin granules. This is illustrated by in vitro and in vivo observations discussed in the present review. Mitochondria generate ATP, which is the main coupling messenger in insulin secretion. However, the subsequent Ca2+ signal in the cytosol is necessary but not sufficient for full development of sustained insulin secretion. Hence, mitochondria generate ATP and other coupling factors serving as fuel sensors for the control of the exocytotic process. Numerous studies have sought to identify the factors that mediate the amplifying pathway over the Ca2+ signal in glucose-stimulated insulin secretion. Predominantly, these factors are nucleotides (GTP, ATP, cAMP, NADPH), although metabolites have also been proposed, such as long-chain acyl-CoA derivatives and glutamate. Hence, the classical neurotransmitter glutamate receives a novel role, that of an intracellular messenger or co-factor in insulin secretion. This scenario further highlights the importance of glutamate dehydrogenase, a mitochondrial enzyme well recognized to play a key role in the control of insulin secretion. Therefore, additional putative messengers of mitochondrial origin are likely to participate in insulin secretion.     

Absence of endotoxin-fever but not hyperthermia in Brattleboro rats

I.c.v. administration of bacterial endotoxin produced a fever in the Long-Evans rat but not in the Brattleboro rat. Similar administration of arachidonic acid, prostaglandin E2, prostacyclin, dibutyryl cAMP, norepinephrine, morphine and beta-endorphin caused hyperthermia in both Long-Evans and Brattleboro rats. Variable doses of exogenous arginine vasopressin (AVP) when centrally administered with endotoxin caused fever in the Brattleboro rat. It is suggested that AVP may play an important role in the production and release of endogenous pyrogen.     

Desensitization of adrenal tumor cells Y1 by ACTH and dibutyryl cyclic AMP]

The steroidogenic responsiveness of mouse adrenal tumor cell line (Y-1) to ACTH and db cAMP declines after stimulations by these compounds. The desensitization induced by ACTH appears early and is more pronounced than that induced by db cAMP. After removal of the hormone or the nucleotide, the recovery of cell responsiveness to both stimuli isprogressively restored. Full responsiveness is recovered within 24 hrs.     

Gonadotrophin-releasing activity of histones H2A and H2B

We report that histones H2A and H2B possess gonadotrophin-releasing activity in vitro and assess the signal transduction pathways involved in these effects. Perifused and incubated rat anterior pituitary (AP) cells were used, and luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by RIA. Perifusion of cells with histone H2A (30 μM) or histone H2B (30 μM), markedly stimulated LH release but failed to elicit any FSH response. Cells incubated with 6 or 30 μM histone H2A showed a dose- and time-dependent stimulatory effect on both LH and FSH release which was blocked by 1 μM peptide MB35, an 86–120 amino acid fragment of histone H2A. Incubation of pituitary cells with gonadotrophin-releasing hormone (GnRH) and histones H2A or H2B showed a stimulatory effect on LH and FSH release which was similar to the sum of the separate effects. Trifluoperazine, as well as ethylene glycol bis(b-aminoethyl ether) N,N,N′,N′-tetraacetic acid (EGTA), alone or in the presence of the calcium ionophore A23187, significantly reduced the response of AP cells to histones. Various cyclic adenosine monophosphate (cAMP) enhancers had no effect on histone-stimulated release of gonadotrophins in incubated AP cells. Our results confirm previous evidence that histones may act as hypophysiotrophic signals. Calcium- and diacylglycerol-associated pathways, but not cAMP, appear to participate in these effects. Received 11 August 1997; received after revision 20 January 1998; accepted 26 January 1998     

Changes in the level of ACTH in the fetal hypophysis. A study in the rat toward the end of gestation]

The isolated adrenal cell method for bioassay of ACTH was employed in order to determine the ACTH content of the hypophysis of the rat foetus, in late pregnancy. The ACTH concentration decreases between 17 days 8 h and 17 days 15 h, then it increases regularly until the term. This evolution is correlated with the change in the fluorescence intensity of the corticotrophs and with the modification of the adrenocortical activity.     

Absence of endotoxin-fever but not hyperthermia in Brattleboro rats

Summary I. c. v. administration of bacterial endotoxin produced a fever in the Long-Evans rat but not in the Brattleboro rat. Similar administration of arachidonic acid, prostaglandin E₂, prostacyclin, dibutyryl cAMP, norepinephrine, morphine and -endorphin caused hyperthermia in both Long-Evans and Brattleboro rats. Variable doses of exogenous arginine vasopressin (AVP) when centrally administered with endotoxin caused fever in the Brattleboro rat. It is suggested that AVP may play an important role in the production and release of endogenous pyrogen.     

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE

We investigated whether hypothalamic prostaglandin E2 (PGE2) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 alpha (IL-1 alpha). The present results show that ACTH responses induced by intravenous injection of IL-1 alpha were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE2 stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE2. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE2.     

Action potentials in non-tumor cells from the anterior pituitary gland

Non-tumor cells of rat anterior pituitary gland are able, upon electrical stimulation, to generate action potentials which are based on an increase of the membrane permeability to both Na+ and Ca2+.     

Differences in luteinizing hormone release stimulated in rat anterior pituitary cells by leukotriene C4 and by gonadotropin-releasing hormone in vitro

Continuous administration of leukotriene C4 (LTC4, 10(-10) M) to superfused rat anterior pituitary cells increased LH release for 40 min only, whereas in a parallel experiment gonadotropin-releasing hormone (GnRH, 10(-9) M) evoked a continuous increase in hormone secretion. In contrast to GnRH, LTC4 did not desensitize rat anterior pituitary cells. The secretory action resulting from the administration of LTC4 (10(-10) M) was abolished for 40 min after previous stimulation. The results documented the dual action of LTC4 on LH exocytosis.     

Opioids and cytosolic calcium in rat anterior pituitary: dynorphin preparation showed LHRH-like action due to contamination

The effect of dynorphin A-(1-13) (Dyn A-(1-13] and other opioids on the cytosolic free calcium concentration [(Ca2+]i) in rat anterior pituitary cells was examined using the fluorescent indicator fura-2. A commercial synthetic Dyn A-(1-13) preparation elevated [Ca2+]i. Results, which were obtained with receptor antagonists, and in LHRH receptor radioligand binding studies as well as by HPLC combined with LHRH radioimmunoassay, strongly suggest that this effect of the dynorphin preparation was due to contamination with a LHRH-like compound. Dyn A-(1-13), purified by HPLC, as well as Dyn A-(2-13), [Leu5]enkephalin, beta-endorphin, morphine, or U50,488H had no effect on [Ca2+]i. LHRH caused a rapid increase in [Ca2+]i by about 50 nM which was blocked by the LHRH antagonist, [D-pGlu1,D-Phe2,D-Trp3,6] LHRH.     

Plurihormonality in the secretory granules of the normal human pituitary. An immunoelectron microscopic study

Normal human autopsy anterior pituitary tissue from 5 cases was embedded in LR White resin and immunolabelled using silver-enhanced 5-nm protein A gold probes. Follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), adrenocorticotrophic hormone (ACTH), growth hormone (GH) and prolactin (PRL) were immunolocalised to the level of secretory granule. A two-sided double-labelling method was used to cross-react two hormones at a time with respect to their corresponding antibodies. All possible combinations of the six pituitary hormones were tested. Plurihormonal granules were found that contained LH + FSH, LH + TSH, and FSH + TSH. Each hormone was also found in monohormonal granules. Granule diameter was significantly larger in the pluri as opposed to monohormonal granules.     

Plurihormonality in the secretory granules of the normal human pituitary. An immunoelectron microscopic study

Summary Normal human autopsy anterior pituitary tissue from 5 cases was embedded in LR White resin and immunolabelled using silver-enhanced 5-nm protein A gold probes. Follicle stimulating hormone (FSH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), adrenocorticotrophic hormone (ACTH), growth hormone (GH) and prolactin (PRL) were immunolocalised to the level of secretory granule.A two-sided double-labelling method was used to cross-react two hormones at a time with respect to their corresponding antibodies. All possible combinations of the six pituitary hormones were tested. Plurihormonal granules were found that contained LH+FSH, LH+TSH, and FSH+TSH. Each hormone was also found in monohormonal granules. Granule diameter was significantly larger in the pluri as opposed to monohormonal granules.