Date of Award
1991
Degree Type
Dissertation
Degree Name
Doctor of Philosophy
Abstract
The release of growth hormone (GH) from the somatotrophs of the anterior pituitary is controlled by two hypothalamic hormones growth hormone-releasing factor (GRF) and somatostatin (SRIF). The former stimulates, while the later inhibits the release of GH. cAMP and Ca{dollar}\sp{lcub}2+{rcub}{dollar} are second messengers for GRF. Previous reports suggested that the phosphoinositide second messenger system was an additional pathway for GRF. Our purpose was to examine the role of this system in GRF action. We used perifused dispersed anterior pituitary cells and purified somatotrophs from male rats to ask: (1) Does activation of protein kinase C stimulate the release of GH and are cAMP and Ca{dollar}\sp{lcub}2+{rcub}{dollar} involved? (2) Does SRIF inhibit the effect of protein kinase C activation? (3) Is protein kinase C present in somatotrophs and does GRF activate the enzyme? (4) Does inactivation of protein kinase C alter the GH response to GRF? (5) Does GRF activate phospholipase C?;Activation of protein kinase C with dioctanoyl-rac-glycerol (diC{dollar}\sb8{dollar}) and phorbol 12-myristate 13-acetate (PMA) caused the immediate and transient release of GH from somatotrophs. The increase was accompanied by a small increase in cAMP accumulation. Removal of extracellular Ca{dollar}\sp{lcub}2+{rcub}{dollar} and the Ca{dollar}\sp{lcub}2+{rcub}{dollar} channel blocker nifedipine reduced protein kinase C activator-induced GH release but not cAMP accumulation. SRIF reduced the release of GH induced by diC{dollar}\sb8{dollar} and PMA. These results suggest that cAMP and Ca{dollar}\sp{lcub}2+{rcub}{dollar} may mediate the action of the protein kinase C activators. Protein kinase C activity was present in somatotrophs. Protein kinase C activators caused a translocation of enzyme activity indicating that protein kinase C can be activated in these cells. GRF, however, did not activate protein kinase C. Also, the GH response to GRF was not altered in cells that were unresponsive to diacylglycerol. GRF did not activate phospholipase C in somatotrophs as determined by measuring the levels of individual radiolabelled phosphoinositides and inositol phosphates following GRF treatment.;We conclude that while all of the components of the phosphoinositide second messenger system are present in somatotrophs, GRF does not act through this system to stimulate GH release.
Recommended Citation
French, Michelle Brigid, "The Phosphoinositide Second Messenger System And The Regulation Of The Release Of Growth Hormone From Purified Rat Somatotrophs" (1991). Digitized Theses. 2047.
https://ir.lib.uwo.ca/digitizedtheses/2047