Altered release of growth hormone from dispersed adenohypophysial cells of streptozotocin diabetic rats. II. Effects of a phorbol ester and secretagogues which increase cyclic AMP.
We have shown in the companion paper that somatotrophs dispersed from streptozotocin diabetic rats exhibit altered sensitivity to the natural hypothalamic controlling hormones, growth hormone releasing factor and somatostatin. We have further studied the effects on growth hormone release from dispersed adenohypophysial cells of normal and streptozotocin diabetic rats of stimulation by compounds that increase cyclic 3',5'-adenosine monophosphate formation or inhibit its breakdown and of a phorbol ester. The cells of the diabetic rats had no change in sensitivity in response to either cholera toxin or forskolin. A phosphodiesterase inhibitor caused an equal GH release from cells of both diabetic and normal animals after 60 min of incubation. There was no change in sensitivity of the cells of diabetic animals or in the maximal response of these cells to the phorbol ester 12-O-tetradecanoylphorbol 13-acetate when compared with normal cells. A low calcium medium that blocked growth hormone releasing factor stimulated growth hormone release from normal rat cells also blocked it from the cells of the diabetic rats. These results suggest that the defect in response of the somatotrophs of diabetic animals is specific and only occurs with the hypothalamic hormones and not with other secretagogues.
Sheppard
M S
MS
Department of Medicine, University of Saskatchewan, Saskatoon, Canada.
Eatock
B A
BA
Bala
R M
RM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D005576:Colforsin; D013004:Somatostatin; D013006:Growth Hormone; D002772:Cholera Toxin; D013007:Growth Hormone-Releasing Hormone; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine