The effects of corticotrophin-releasing hormone, arginine vasopressin and their antagonists on ACTH release from perifused horse anterior pituitary cells

1994 ◽  
Vol 143 (1) ◽  
pp. 85-93 ◽  
Author(s):  
M J Ellis ◽  
R S Mulligan ◽  
M J Evans ◽  
R A Donald
Keyword(s):  
Arginine Vasopressin ◽  
Anterior Pituitary ◽  
Dose Range ◽  
Inhibitory Effect ◽  
Pituitary Cells ◽  
Releasing Hormone ◽  
Anterior Pituitary Cells ◽  
The Individual ◽  
Acth Release

Abstract Antagonists are useful for probing hormone action and receptor characteristics. In this study we have investigated the inhibitory effects of analogues of arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) on stimulated release of immunoreactive ACTH from perifused equine anterior pituitary cells in vitro. Our aims were to gain some insight into the characteristics of the CRH and AVP receptors of the horse pituitary and to establish whether the response induced by AVP and CRH together could be blocked by combining antagonists. Experimental design included 5-min pulses of AVP (12·5 nmol/l), CRH (0·3 nmol/l) or CRH plus AVP given every 40 min alternately with pulses of secretagogue(s) plus appropriate antagonist(s). The effect of combined antagonists on the response to lower secretagogue concentrations (CRH, 0·03 nmol/l plus AVP, 2·5 nmol/l) was also tested. Response in the presence of an antagonist was compared with the mean response to secretagogue in the immediately preceding and following pulse and was expressed as per cent expected ACTH. The ACTH response to AVP was inhibited over the dose range 0·4–50 μmol/l by Phaa-d-Tyr(Et)2Lys6Arg3VP (P<0·002; ANOVA) and by d(CH2)5[Tyr(Me)2]AVP (P<0·001). Suppression of the expected ACTH response to AVP by these two antagonists was most effectively achieved by antagonist concentrations of 10 μmol/l (to 28±2·1%) and 25 μmol/l (to 22±5·1%) respectively. Inhibition was not improved by preinfusion compared with a bolus pulse. Aaa-d-Tyr(Et)2Val4Abu6Arg8·9VP and the non-peptide antagonist OPC-21268 had no inhibitory effect. Two α-helical (α-h) analogues of CRH, (α-hCRH(12–41) and α-hCRH(9–41) tested over the dose range 0·5–5 μmol/l, suppressed CRH-induced ACTH secretion (P<0·001) but CRH(23–41) had no significant effect. The α-hCRH(12–41) achieved greater suppression of ACTH release than the (9–41) derivative (8·7±4·2% compared with 19·3±3·5% of the expected ACTH response). Combination of d(CH2)5[Tyr(Me)2]AVP (25 μmol/l) plus α-hCRH (12–41) (5·0 μmol/l) achieved suppression to −0·5±1·3% and 0·8±1·5% of the expected response to CRH+AVP at 0·3+12·5 nmol/l and 0·03+2·5 nmol/l respectively. These effects were greater than seen by the individual antagonists alone. The antagonist effects suggest that the CRH and AVP receptors of the equine pituitary have similar properties to those from other species and are consistent with the pituitary AVP receptor being unlike the V2 receptor and resembling but not being identical to the V1 type. We also conclude that α-hCRH(12–41) and d(CH2)5[Tyr(Me)2]AVP can together block the ACTH response to CRH plus AVP and suggest that these antagonists should provide a means of investigating additional secretagogues involved in ACTH release in the horse. Journal of Endocrinology (1994) 143, 85–93

scholarly journals Desensitization of the adrenocorticotrophin responses to arginine vasopressin and corticotrophin-releasing hormone in ovine anterior pituitary cells

2003 ◽  
Vol 178 (3) ◽  
pp. 491-501 ◽  
Author(s):  
A Hassan ◽  
S Chacko ◽  
D Mason
Keyword(s):  
Arginine Vasopressin ◽  
Anterior Pituitary ◽  
Prolonged Exposure ◽  
No Reduction ◽  
Pituitary Cells ◽  
Acth Secretion ◽  
Releasing Hormone ◽  
Anterior Pituitary Cells

Following repeated or prolonged exposure to either corticotrophin-releasing hormone (CRH) or arginine vasopressin (AVP), pituitary adrenocorticotrophin (ACTH) responsiveness is reduced. This study compared the characteristics of desensitization to CRH and AVP in perifused ovine anterior pituitary cells. Desensitization to AVP occurred at relatively low AVP concentrations and was both rapid and readily reversible. Treatment for 25 min with AVP at concentrations greater than 2 nM caused significant reductions in the response to a subsequent 5 min 100 nM AVP pulse (IC(50)=6.54 nM). Significant desensitization was observed following pretreatment with 5 nM AVP for as briefly as 5 min. Desensitization was greater following a 10 min pretreatment, but longer exposures caused no further increase. Resensitization was complete within 40 min following 15 min treatment with 10 nM AVP. Continuous perifusion with 0.01 nM CRH had no effect on AVP-induced desensitization. Treatment with 0.1 nM CRH for either 25 or 50 min caused no reduction in the response to a subsequent 5 min stimulation with 10 nM CRH. When the pretreatment concentration was increased to 1 nM significant desensitization was observed, with a greater reduction in response occurring after 50 min treatment. Recovery of responsiveness was progressive following 50 min treatment with 1 nM CRH and was complete after 100 min. Our data show that in the sheep AVP desensitization can occur at concentrations and durations of AVP exposure within the endogenous ranges. This suggests that desensitization may play a key role in regulating ACTH secretion in vivo. If, as has been suggested, CRH acts to set corticotroph gain while AVP is the main dynamic regulator, any change in responsiveness to CRH may significantly influence the overall control of ACTH secretion.

Stimulatory effect of thyrotrophin-releasing hormone (TRH) on the release of luteinizing hormone (LH) from rat anterior pituitary cells in vitro

1983 ◽  
Vol 61 (2) ◽  
pp. 186-189 ◽  
Author(s):  
Noboru Fujihara ◽  
Masataka Shiino
Keyword(s):  
Luteinizing Hormone ◽  
Anterior Pituitary ◽  
Pituitary Cells ◽  
Thyrotrophin Releasing Hormone ◽  
Releasing Hormone ◽  
Anterior Pituitary Cells ◽  
Lh Release ◽  
Lh Rh

The effect of thyrotrophin-releasing hormone (TRH, 10−7 M) on luteinizing hormone (LH) release from rat anterior pituitary cells was examined using organ and primary cell culture. The addition of TRH to the culture medium resulted in a slightly enhanced release of LH from the cultured pituitary tissues. However, the amount of LH release stimulated by TRH was not greater than that produced by luteinizing hormone – releasing hormone (LH–RH, 10−7 M). Actinomycin D (2 × 10−5 M) and cycloheximide (10−4 M) had an inhibitory effect on the action of TRH on LH release. The inability of TRH to elicit gonadotrophin release from the anterior pituitary glands in vivo may partly be due to physiological inhibition of its action by other hypothalamic factor(s).

Secretion of adrenocorticotrophin (ACTH) and ACTH precursors in ovine anterior pituitary cells: actions of corticotrophin-releasing hormone, arginine vasopressin and glucocorticoids

1994 ◽  
Vol 140 (2) ◽  
pp. 189-195 ◽  
Author(s):  
J Schwartz ◽  
P Ash ◽  
V Ford ◽  
H Raff ◽  
S Crosby ◽  
...  
Keyword(s):  
Arginine Vasopressin ◽  
Anterior Pituitary ◽  
Secretory Response ◽  
Target Cells ◽  
Pituitary Cells ◽  
Basal Secretion ◽  
Acth Secretion ◽  
Releasing Hormone ◽  
Anterior Pituitary Cells ◽  
Synthetic Glucocorticoid

Abstract Although corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) have been extensively characterized as stimulators, and glucocorticoids as inhibitors of ACTH secretion, far less is known about the control of the secretion of ACTH precursors from the anterior pituitary or about the types of corticotrophs involved. The present study was designed to systematically evaluate the actions of stimulatory and inhibitory factors on the secretion of ACTH and ACTH precursors (pro-opiomelanocortin, Mr 31 000; pro-ACTH, Mr 22 000) from dissociated ovine anterior pituitary cells. The cells were stimulated for 3 h with CRH (10 nmol/l) and AVP (100 nmol/l), alone or in combination with the synthetic glucocorticoid dexamethasone. In designated wells, cells were treated with dexamethasone, (100 nmol/l), beginning 16–18 h before and continuing through the 3-h secretion experiments in the presence of CRH and AVP. Secretion of ACTH-like peptides from intact cultures was compared with that from cultures which had been pretreated with a cytotoxic CRH conjugate (cytotoxin) to eliminate CRH-target cells specifically. Immunoreactive (ir)-ACTH was measured by radioimmunoassay (RIA); ACTH(1–39) and ACTH precursors were specifically measured by two-site immunoradiometric assays that discriminate between the two. In intact populations of cells, dexamethasone had no effect on basal ACTH(1–39) secretion, but decreased the secretion of ACTH(1–39) in response to CRH or AVP. Pretreatment of cells in the same experiments with cytotoxin (for 18 h, beginning 3·5 days before secretion studies) also had no significant effect on basal ACTH(1–39) secretion, but eliminated the response to CRH and decreased the response to AVP. In contrast to the situation in intact populations, dexamethasone had no effect on the residual secretion of ACTH(1–39) in response to AVP. These results mirrored those for secretion of ir-ACTH, measured by RIA. Secretion of ACTH precursors followed a different pattern from that for ir-ACTH and ACTH(1–39). In intact populations, dexamethasone decreased the secretion of ACTH precursors in response to CRH, but had no effect on basal secretion or the precursor response to AVP. Elimination of CRH-target cells also had no effect on basal precursor secretion and eliminated the secretion of precursors in response to CRH. Loss of CRH-target cells was accompanied by a smaller decrease in the secretion of ACTH precursors than ir-ACTH and ACTH(1–39) in response to AVP. Interestingly, dexamethasone significantly increased the secretion of ACTH precursors in response to AVP after cytotoxin. These results suggest either that the inhibition by glucocorticoids of the ACTH(1–39) secretory response to AVP is confined to those AVP-responsive cells that are sensitive to the CRH-target-specific cytotoxin, or that glucocorticoid-induced inhibition of the response to AVP depends on the functional presence of CRH-responsive cells. The results further suggest that the secretion of ACTH precursors in response to AVP is resistant to inhibition by glucocorticoids, regardless of the presence of CRH-target cells and is, generally, much less influenced by, or dependent upon, CRH-target cells. Taken together, the data suggest that those corticotrophs which are resistant to cytotoxin are the source of ACTH precursors secreted in response to AVP, and resist inhibition by glucocorticoids. Journal of Endocrinology (1994) 140, 189–195

CORTICOTROPHIN-RELEASING FACTOR - MEDIATED ADRENOCORTICOTROPHIN RELEASE FROM RAT ANTERIOR PITUITARY CELLS IS POTENTIATED BY C-TERMINAL GASTRIN-RELEASING PEPTIDE

1984 ◽  
Vol 102 (2) ◽  
pp. R1-R3 ◽  
Author(s):  
A.C. Hale ◽  
J. Price ◽  
J.F. Ackland ◽  
I. Doniach ◽  
S. Ratter ◽  
...  
Keyword(s):  
Anterior Pituitary ◽  
In Vitro Release ◽  
Surgical Removal ◽  
Pituitary Cells ◽  
Gastrin Releasing Peptide ◽  
Corticotrophin Releasing Factor ◽  
Anterior Pituitary Cells ◽  
Isolated Rat ◽  
Acth Release

ABSTRACT The remission of Cushing's syndrome following surgical removal of a tumour containing bombesin-like immunoreactivity (BLI), but insignificant levels of ACTH, is described. However, an acid extract of the tumour tissue caused the release of ACTH from isolated rat anterior pituitary cells in vitro. These observations led to an investigation of the effects of synthetic C-terminal gastrin-releasing peptide (GRP(14-27)) on ACTH release from isolated rat anterior pituitary cells. GRP(14-27) (10-1000 ng/ml) directly stimulated the release of ACTH in vitro, whereas lower doses (10-1000 pg/ml), ineffective themselves in eliciting ACTH release, potentiated the CRF-mediated in-vitro release of ACTH.

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