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 reponse 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.Key words: growth hormone, diabetes, streptozotocin, cyclic AMP, phorbol ester.

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Altered release of growth hormone from dispersed adenohypophysial cells of streptozotocin diabetic rats. I. Effects of growth hormone releasing factor and somatostatin

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-209 ◽

1989 ◽

Vol 67 (10) ◽

pp. 1315-1320 ◽

Cited By ~ 3

Author(s):

M. S. Sheppard ◽

B. A. Eatock ◽

R. M. Bala

Keyword(s):

Growth Hormone ◽

Early Morning ◽

Serum Glucose ◽

Diabetic Rats ◽

Hormone Release ◽

Growth Hormone Release ◽

Growth Hormone Releasing Factor ◽

Rat Growth ◽

Streptozotocin Diabetic Rats

As growth hormone has been implicated in the "dawn phenomenon," an early morning rise in serum glucose, we have studied the control of growth hormone release in diabetes using an acutely dispersed system of adenohypophysial cells from normal or diabetic rats (65 mg/kg streptozotocin, 8 days before sacrifice; serum glucose, 490 ± 17 mg/dL). Growth hormone release is normally controlled by the two hypothalamic hormones, growth hormone releasing factor and somatostatin. We have found cells of the diabetic rats exhibit changes in sensitivity that result in increased growth hormone release in static incubation. In normal cells, rat growth hormone releasing factor increases growth hormone release three- to four-fold with an EC50 of 151 ± 27 pM (n = 7). In contrast, in cells from diabetic rats, there was a significant (twofold) increase in sensitivity to growth hormone releasing factor (EC50 = 75 ± 15 pM, n = 7) which resulted in increased growth hormone release with lower but not maximal (10 nM) growth hormone releasing factor. Basal nonstimulated release was unchanged. Somatostatin inhibition of stimulated growth hormone release was reduced (n = 7); half-maximal inhibition occurred with 0.21 ± 0.03 nM (normal) and 0.76 ± 0.17 nM somatotatin (diabetic). In perifusion the peak secretion rate was significantly lower for diabetic cells stimulated by a maximal dose of growth hormone releasing factor. These studies suggest somatotrophs of diabetic rats have altered sensitivity in vitro to the controlling hormones growth hormone releasing factor and somatostatin.Key words: growth hormone, diabetes, streptozotocin, growth hormone releasing factor, somatostatin.

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Ectopic Growth Hormone-Releasing Factor and Dibutyryl Cyclic Adenosine Monophosphate-Stimulated Growth Hormone Release in Vitro: Effects of Corticosterone and Estradiol*

Endocrinology ◽

10.1210/endo-113-4-1191 ◽

1983 ◽

Vol 113 (4) ◽

pp. 1191-1196 ◽

Cited By ~ 26

Author(s):

CHERYLE B. WEBB ◽

MARTA SZABO ◽

LAWRENCE A. FROHMAN

Keyword(s):

Growth Hormone ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Hormone Release ◽

Growth Hormone Release ◽

Growth Hormone Releasing Factor ◽

Release In Vitro ◽

In Vitro Effects

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Increase in pituitary adenosine 3′:5′-cyclic monophosphate content and potentiation of growth-hormone release from heifer anterior pituitary slices incubated in the presence of 3-isobutyl-1-methylxanthine

Biochemical Journal ◽

10.1042/bj1420295 ◽

1974 ◽

Vol 142 (2) ◽

pp. 295-300 ◽

Cited By ~ 10

Author(s):

J. George Schofield ◽

Margaret McPherson

Keyword(s):

Growth Hormone ◽

Cyclic Amp ◽

Prostaglandin E2 ◽

Anterior Pituitary ◽

Phosphodiesterase Inhibitor ◽

Secretory Process ◽

Hormone Release ◽

Growth Hormone Release ◽

Inhibitor Concentration ◽

Stimulation Of

The release of growth hormone from heifer anterior pituitary slices and the cyclic AMP content of the slices were increased by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, both increases being related to inhibitor concentration over the range 0.1–1.0mm. Neither Ba2+(6.9 or 2.3mm), K+(72mm), nor p-chloromercuribenzoate (20μm) had any effect on pituitary cyclic AMP content over a 20min period. 3-Isobutyl-1-methylxanthine potentiated the release of growth hormone in response to Ba2+(2.3mm) and K+(24mm), but the degree of potentiation did not depend on inhibitor concentration in the same way as did tissue cyclic AMP content. 3-Isobutyl-1-methylxanthine decreased the concentration of K+required to give maximum stimulation of growth-hormone release, but did not significantly increase the maximum response to Ba2+. Growth-hormone release in the presence of prostaglandin E2 (1μm) was increased by 3-isobutyl-1-methylxanthine and was inhibited by the prostaglandin antagonist, 7-oxa-13-prostynoic acid, although this antagonist increased the pituitary cyclic AMP concentration and potentiated the prostaglandin E2-induced rise in cyclic AMP content. The stimulation of growth-hormone release by p-chloromercuribenzoate was not potentiated by 3-isobutyl-1-methylxanthine. The data suggest that Ba+and K+act at the same point in the secretory process as 3-isobutyl-1-methylxanthine, although by a different mechanism, and that p-chloromercuribenzoate has a different point of action.

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