Search PubMed⌕ Search

Biomedical subjects

C P Fawcett

Publications and source records attributed to C P Fawcett.

At least 19 recordsLinked to original sources
PubMed1989

Oxytocin stimulates glucagon and insulin secretion in fetal and neonatal sheep.

In adults of several species arginine vasopressin (AVP) and oxytocin (OT) stimulate pancreatic secretion of immunoreactive plasma glucagon (IRG). In fetal sheep AVP is an important stress hormone and may be simultaneously secreted with OT; however, their effects on IRG secretion are not known. We sought to determine if AVP and/or OT affected pancreatic IRG secretion in fetal and neonatal sheep. Either AVP or OT was infused for 30 min in chronically catheterized fetal and neonatal sheep, obtaining peripheral arterial and/or portal venous blood samples before; 10, 15, and 30 min during; and 15, 30, and 60 min after infusion for measurements of blood gases, hematocrit, IRG, immunoreactive plasma insulin (IRI) and plasma glucose. AVP did not affect IRG or IRI in fetal sheep (mean +/- SE, 133 +/- 1 days gestation), but small increases occurred in portal venous blood of lambs (2-49 days old). In contrast, OT (4.6 +/- 0.3 mU/min.kg; n = 12) increased fetal plasma IRG from 72 +/- 5 to 86 +/- 6 and 97 +/- 7 pg/ml (P less than 0.001) and IRI from 16 +/- 2 to 20 +/- 3 and 20 +/- 2 microU/ml (P less than 0.02) at 15 and 30 min, respectively; 157 +/- 11 microU OT/min.kg had no effect. In lambs (2-49 days old), 3.0 mU OT/min.kg increased arterial (n = 15) IRG from 139 +/- 19 to 367 +/- 43 and 483 +/- 76 pg/ml (P less than 0.01) and portal IRG (n = 8) from 167 +/- 39 to 341 +/- 72 and 502 +/- 148 pg/ml (P less than 0.01), respectively. Arterial and portal IRI also rose (P less than 0.01) from 36 +/- 4 to 82 +/- 12 and 105 +/- 32 microU/ml and from 29 +/- 5 to 65 +/- 13 and 51 +/- 7 microU/ml, respectively. Glucose was unchanged in all experiments. In fetal and neonatal sheep, AVP has minimal effects on IRG and IRI release. In contrast, OT increases both substantially; furthermore, there is a difference in fetal and neonatal responsiveness. OT may be important in modulating glucagon and insulin secretion during and after parturition.

Animals↗
PubMed1985

Corticotropin-releasing factor inhibits insulin release from perfused rat pancreas.

The ability of synthetic corticotropin-releasing factor (CRF) (rat) to influence hormone release from the endocrine pancreas of rats has been evaluated by means of perfusion in situ. Release of insulin and glucagon into the perfusate was measured in the presence and absence of CRF (0.1, 1, and 10 ng/ml) under conditions of normal and high glucose concentration (5.5 and 11 mM). Under both conditions, CRF (0.1, 1, and 10 ng/ml) induced a rapid, dose-dependent inhibition of insulin release followed by a remarkable postinhibitory rebound when exposure to CRF was discontinued. CRF had no significant effect on glucagon release when tested under these conditions. These results are reminiscent of noradrenergic inhibition of insulin release and together with evidence for the presence of CRF in the pancreas suggest that this peptide could function as a neuromodulatory transducer in addition to its role as a hypophysiotropic hormone perhaps contributing to the coordination of the overall endocrine response to stress.

Animals↗
PubMed1985

Evidence for participation of the neurohypophysial hormones in the hyperglucagonemic response to hemorrhage in the rat.

Conscious adult male rats bearing jugular cannulae were injected with either normal rabbit serum (NRS) or with serum containing antibodies to both oxytocin (OT) and arginine vasopressin (AVP). In the NRS-treated group, plasma levels of OT, AVP and immunoreactive glucagon (IRG) were significantly elevated 10 min after hemorrhage (2.3 ml/100 g body weight over 5 min) whereas hyperglucagonemia was not detected in the antiserum-treated group until 30 min posthemorrhage. In animals which were deprived of water during the experiment, plasma IRG in the antiserum-treated group reached only 40% of the levels in the NRS-treated controls. These results suggest that hemorrhage-induced elevations in circulating AVP and/or OT contribute to increased release of glucagon by the endocrine pancreas consistent with previous demonstration of glucagonotropic activity of synthetic neurohypophysial peptides.

Animals↗
PubMed1985

Corticotropin-releasing factor: its action on the islets of Langerhans.

Synthetic rat and ovine CRF were tested in an in vitro isolated pancreatic islet system for their ability to influence insulin and glucagon release. Acute exposure of islets to both rat and ovine CRF resulted in a significant increase in glucagon release but only over a narrow range of concentration (50-200 pg/ml). Neither peptide had a significant effect on insulin release. Our results raise the possibility that release of glucagon may be stimulated by CRF as part of the overall response to stress.

Animals↗
PubMed1984

Hypothalamic lesions in the weanling rat alter pancreatic response to glucose.

Circulating levels of insulin and glucagon were monitored daily in weanling rats bearing bilateral radiofrequency lesions of the hypothalamic region comprising the ventral pole of the dorsomedial nucleus and at least one third of the dorsal pole of the ventromedial nucleus (V-DMH). Plasma insulin levels in the animals with lesions were significantly elevated by the eighth post-lesion day while plasma glucagon levels were significantly reduced by the 13th day. An intravenous glucose bolus administered to conscious unrestrained animals with lesions had no significant effect on circulating insulin levels but resulted in a dramatic increase in circulating glucagon levels. The IV glucose injections had no significant effect on circulating glucagon levels in the sham-lesioned and unoperated controls while the plasma insulin levels in both control groups were significantly elevated. After a glucose challenge in vitro (300 mg%), insulin release by islets from the lesioned animals showed only a slight increase whereas glucagon release was paradoxically increased. These results provide evidence for an abnormal glucose-sensing function of the pancreatic islet after hypothalamic lesions.

Animals↗
PubMed1984

Actions of neurohypophysial peptides on pancreatic hormone release.

The intermittent reports concerning metabolic actions of neurohypophysial extracts or hormones encouraged us to study the effect of these substances on the function of the endocrine pancreas. A surprisingly small amount of neural lobe (NL) extract (0.025 NL eq/ml) stimulated a 425% increase in the release of glucagon from islets isolated from the pancreas of the rat. Gel filtration of the extract produced an elution profile of glucagon-releasing activity that was superimposable on the profiles of oxytocin (OT) and arginine vasopressin (AVP). Synthetic OT and AVP each elicited a concentration-dependent stimulation of glucagon release but failed to influence insulin release in medium 199 containing 5.6 mM glucose. They were effective at 0.2 ng/ml (+55%, +50%) and produced a striking increase (five- to sevenfold) at 20 ng/ml. The response to each peptide was greatly diminished in the presence of a higher concentration of glucose (11 mM). The lysine, desamino-, and 1,6-aminosuberyl analogues of vasopressin, vasotocin, and AVP are equipotent peptides, whereas the desglycinamide analogue, pressinoic acid, and angiotensin II were inactive. Injection of AVP (1 microgram iv) produced a rapid increase in peripheral glucagon (+185% in 5 min). The response to injection of OT was less rapid (+105% in 15 min), but in each case elevation of insulin was also observed. Our results provide evidence that OT and AVP can act directly on the endocrine pancreas and may help explain previous reports of metabolic actions of these peptides.

Animals↗
PubMed1983

Purification of a glucagon releasing factor from the rat hypothalamus.

The purification of a peptide from the rat hypothalamus which is capable of stimulating the release of glucagon from the endocrine pancreas and therefore named glucagon releasing factor (GlRF), is described. Compositional analysis of the product obtained using well established techniques for peptide isolation revealed that GlRF appeared to consist of 30-31 amino acids. The significance of GlRF in the physiological regulation of glucagon secretion is yet to be determined but the existence of this very potent factor supports the concept of a hypothalamic-pancreatic neurohormonal link.

Animals↗
PubMed1983

Purification of a bioactive FSH-releasing factor (FSHRF).

Before the advent of radioimmunoassay (RIA), FSH-releasing factor (FSHRF) appeared to be separable from LH-releasing hormone (LHRH) by chromatography followed by bioassay for FSH. In this study, we re-examined hypothalamic extracts for the existence of an FSHRF distinct from LHRH, utilizing the Steelman-Pohley bioassay as well as RIA for identification of FSH. Acid extracts of rat hypothalamic fragments were chromatographed on Sephadex G-25. LH- and FSH-releasing activities of each fraction were assessed by bio- and immunoassay of FSH and immunoassay of LH released after incubation with hemipituitaries from adult male rats. The immunoreactive LHRH(IR-LHRH) concentration of each fraction was also measured by RIA. In order to evaluate the FSH-releasing activity of LHRH, three doses of synthetic LHRH were tested and FSH-releasing activity determined by bio- and immunoassay. By RIA, the FSH-releasing activity of each column fraction could be accounted for by IR-LHRH contamination. However, greater FSH-releasing activity than could be predicted by IR-LRH contamination was detected by Steelman-Pohley assay in fractions eluted prior to the LHRH peak in 2 separate fractionations. These fractions from the second fractionation were pooled and eluted from a CMC column with ammonium acetate buffers. Again greater FSH-releasing activity than could be accounted for by IR-LHRH was detected prior to the IR-LHRH peak by Steelman-Pohley assay. These results agree with early work from our laboratory and suggest the presence of a bioactive FSHRF in hypothalamic extracts.

Animals↗
PubMed1981

Action of thyrotropin-releasing hormone on mammotrophs and thyrotrophs.

Anterior pituitary cells from 15-day female rats were separated by unit gravity sedimentation into four populations (designated regions I-IV) based on the profile of cell distribution and the resulting content of radioimmunoassayable (RIA) hormones. The cells in regions II and IV released thyrotropin (TSH) in response to thyrotropin-releasing hormone (TRH, 5 ng/ml); however, those in region IV released only approximately 5% of their RIA content, whereas those in region II released approximately 26% in response to the same stimulus. Concomitant elevation of cAMP and of cGMP occurred in region II cells but only cGMP was elevated in region IV cells. Mammotrophs were localized in region III. They responded to TRH by releasing prolactin (PRL) and exhibiting increased cAMP content. These data provide support for the existence of two functionally distinct populations of thyrotrophs in 15-day-old female rats. The data also imply that cAMP is involved in TRH induced PRL release, whereas cGMP is involved in TRH-induced TSH release.

Animals↗
PubMed1980

Chromatographic and biologic analysis of ME and OVLT LHRH.

The luteinizing hormone (LH)-releasing activities a pooled rat organum vasculosum lamina terminalis (OVLT) and median eminence (ME) tissues were evaluated for chromatographic and biologic similarity and compared to those of synthetic decapeptide LH-releasing hormone (LHRH). The LHRH detected in these extracts appeared similar chromatographically (Sephadex G-25) to synthetic LHRH. These extracts, as well as synthetic LHRH, were also capable of stimulating dose dependent gonadotropin release form cultures rat gonadotrophs. These findings suggest a physiological role of the LHRH present in the rat OVLT in the control of gonadotropin secretion.

Animals↗
PubMed1980

Gonadotropin release and cyclic nucleotides: evidence for luteinizing hormone-releasing hormone-induced elevation of guanosine 3',5'-monophosphate levels in gonadotrophs.

To investigate the participation of cyclic nucleotides in LHRH-mediated gonadotropin release, cells from the anterior pituitaries of 15-day-old female rats were fractionated on an albumin gradient by sedimentation at unit gravity. gonadotrophs and somatotrophs were detected in the fractions by histology and RIA of hormone content, then the cells were pooled into three subpopulations and cultured overnight. The effect of LHRH on hormone release and cyclic nucleotide content was examined by incubation in the presence or absence of the releasing hormone. After 60 min, LHRH (5 nM) had induced a 5- to 6-fold increase in LH release only from the cells in the subpopulation which was enriched in gonadotrophs. At no time did LHRH influence cAMP levels in any of the cells; however, the cGMP content of the cells in the gonadotroph-containing pool rose to twice that in the controls after only 15 min in the presence of LHRH. The increase in cGMP concentration in the cells was at or near maximum by the time of the initial sampling; however, LH continued to accumulate in the medium over the entire test period. These observations support the view that cGMP is involved in the action of LHRH.

Animals↗
PubMed1979

Differential effects of castration and testosterone replacement on basal and LHRH-stimulated cAMP and cGMP accumulation and on gonadotropin release from the pituitary of the male rat.

Castration of male rats decreased cAMP levels, and increased cGMP levels and gonadotropin release from anterior pituitaries incubated in vitro. Testosterone (T) replacement via silastic tubes filled with the steroid increased cAMP and decreased cGMP levels and gonadotropin release. Incubation of hemipituitaries from intact males with luteinizing hormone releasing hormone (LHRH, 5 nM for 2 h) resulted in increased cAMP and cGMP accumulation and gonadotropin release. Castration abolished LHRH-induced cAMP accumulation, but increased the effect of LHRH on cGMP accumulation and gonadotropin release. Testosterone replacement restored cAMP stimulation by LHRH but decreased LHRH-induced elevation of cGMP levels and gonadotropin release. These data illustrate parallel increases by castration of LHRH-induced cGMP accumulation and of gonadotropin release. Furthermore, these two parameters are influenced in the opposite direction by replacement therapy. These results support the concept of a role for cGMP in LHRH action as well as providing evidence of a link between the feedback action of T and cGMP in the pituitary gland.

Animals↗
PubMed1979

Histaminergic involvement in thyrotropin-releasing hormone stimulation of antral tissue in the rat.

The mechanism of action of thyrotropin-releasing hormone on antral motility was investigated in vitro. With the recent detection of thyrotropin-releasing hormone in gastrointestinal tissue, the possibility exists that the peptide may play a physiologic role in gastrointestinal motility. Results indicate that the hormone stimulates antral motility through a non-cholinergic excitatory pathway based on the inability of the muscarinic antagonist, atropine, to block the response. A histaminergic pathway is an attractive possibility to explain the excitatory response, because both pyrilamine and cimetidine inhibit the thyrotropin-releasing hormone induced response and the peptide has no further influence on antral motility after the tissue is exposed to a supramaximal concentration of histamine.

Animals↗
PubMed1978

Involvement of cGMP in LHRH-stimulated gonadotropin release.

Anterior pituitary content of cyclic AMP (cAMP) and cyclic GMP (cGMP) has been measured during stimulation of gonadotropin release by luteinizing-hormone-releasing hormone (LHRH) in vitro to gain more information concerning the relationship between the mechanism of action of LHRH and cyclic nucleotides. During the increased gonadotropin release obtained by incubation by hemipituitaries with LHRH (0.25--25 X 10(-9) M) for 180 min, the glands taken from both male and female rats exhibited increased cGMP content, whereas cAMP content rose only in those taken from male rats. The increase in cGMP content was observed after only 2 min in the presence of LHRH (5 X 10(-9) M) and prior to augmented gonadotropin release. The increase in cAMP content in the male glands was detectable only after 60 min of incubation. These results suggest that cGMP might be involved in the mechanism of action of LHRH.

Animals↗
PubMed1978

Evidence for the involvement of guanosine 3',5'-cyclic monophosphate in the regulation of gonadotropin release.

Addition of dibutyryl adenosine 3'-5'-cyclic monophosphate (DBcAMP) or dibutyryl guanosine 3',5'-cyclic monophosphate (DBcGMP; 1--6mM) to to enzymatically dispersed, overnight-cultured rat anterior pituitary cell preparations stimulated the release of gonadotropins (LH and FSH) from the cells into the incubation medium. Stimulation of gonadotropin release by DBcGMP was observed after only 10 min of incubation, whereas that caused by DBcAMP appeared at 180 min. Synthetic LHRH (2.5 X 10(-9) M) induced a small, transient increase in intracellular cAMP content (+16%, P less than 0.05, after 5 min coincubation), while levels of cGMP in the same cells were rapidly and markedly low for 2 h. The decrease in cGMP content was accompanied by a discharge of gonadotropins lasting for 2 h, which was detectable after 5 min in the case of LH and after 10 min in the case of FSH. These results strongly suggest that cGMP might be an intracellular mediator in the process of LHRH-stimulated release of gonadotropins.

Animals↗
PubMed1978

A possible role for cyclic GMP in mediating the effect of luteinizing hormone releasing hormone on gonadotropin release in dispersed pituitary cells of the female rat.

In continuing studies on cyclic nucleotide involvement in the regulation of gonadotropin release, we have measured the cyclic nucleotide content and rate of LH and FSH release during stimulation by LHRH of dispersed overnight cultured cells from the pituitaries of adult female rats. The minimal effective concentration of LHRH was 0.1 nM and half maximal stimulation of gonadotropin release was observed in the presence of 1.0 nM LHRH. Significant release of both LH and FSH was detectable after only 10 min in the presence of 5 nM LHRH. The presence of fetal calf serum (FCS) in the overnight culture medium increased basal cGMP levels significantly, whereas horse serum (HS) had no effect, therefore all experiments were conducted on cells cultured in the presence of HS. Treatment of the cultured cells with the phosphodiesterase inhibitors theophylline (TH) or isobutyl-methyl-xanthine (MIX) revealed a preferential stimulatory effect of TH on basal cAMP levels and of MIX on cGMP levels. Throughout these experiments, LHRH had no effect on cAMP levels. In the presence of MIX, concentrations of the releasing hormone as low as 1 nM induced a significant rise in the level of cGMP whereas in its absence, cGMP levels appeared to be unchanged by LHRH. The increase was detectable after 10 min of incubation. MIX alone slightly increased LH and FSH release and significantly potentiated the response of the cells to increasing doses of LHRH up to, but not beyond, 10 nM. The data support the possibility that cGMP may be involved in the mechanism of action of LHRH.

1-Methyl-3-isobutylxanthine↗