Summary
Streptozotocin-induced diabetes causes a decrease in growth hormone and prolactin receptors in the livers of female rats, and in the serum concentration of somatomedin-C/insulin-like growth factor-1, concomitantly with an increase in the serum testosterone levels. In this study, a possible role for adrenal androgens in the loss of receptors was examined. Rats were adrenalectomised bilaterally 3 days after the induction of diabetes with streptozotocin (100 mg/kg intravenously), and livers were removed 3 days later. Adrenalectomy had no effect on binding of ovine prolactin or bovine growth hormone to liver microsomal membranes from non-diabetic rats, but in diabetic rats it entirely abolished the 56% decrease in prolactin binding and significantly reversed the 66% decrease in growth hormone binding and the parallel fall in serum levels of somatomedin-C/insulin-like growth factor-I (p<0.05). Adrenalectomy also prevented the diabetes-induced rise in serum testosterone. Daily injection of testosterone to normal and diabetic rats for 12 days significantly reduced both prolactin and growth hormone binding (p<0.001), with the effect of diabetes being additive upon the testosterone effect. Implantation of testosterone-filled silastic capsules at the time of adrenalectomy (i. e. for 3 days) did not prevent the adrenalectomy-induced restoration of both growth hormone and prolactin receptors. The resulting high serum testosterone level did not reduce binding to growth hormone receptors in control rats over the 3 day period, and caused no further decrease in diabetic rats. However, binding to prolactin receptors was reduced by 47% in control animals with no further loss in diabetic animals (p<0.001). Adrenalectomy prevented the loss of prolactin receptors in both testosterone-treated and diabetic rats. These results indicate that, whether or not the rise in testosterone of adrenal origin contributes to the receptor loss in diabetes, the effect also depends on another factor of adrenal origin.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Baxter RC, Bryson JM, Turtle JR (1980) Somatogenic receptors of rat liver: regulation by insulin. Endocrinology 107:1176–1181
Baxter RC, Bryson JM, Turtle JR (1981) Changes in rat liver prolactin binding sites in diabetes are sex dependent. Metabolism 30:211–215
Klapper DG, Svoboda ME, Van Wyk JJ (1983) Sequence analysis of somatomedin-C: confirmation of identity with insulin-like growth factor I. Endocrinology 112:2215–2217
Baxter RC, Brown AS, Turtle JR (1979) Decrease in serum receptor-reactive somatomedin in diabetes. Horm Metab Res 11:216–220
Maes M, Ketelslegers JM, Underwood LE (1983) Low plasma somatomedin-C in streptozotocin-induced diabetes mellitus. Correlation with changes in somatogenic and lactogenic liver binding sites. Diabetes 32:1060–1069
Leaming AB, Mathur RS, Levine JH (1982) Increased plasma testosterone in streptozotocin-diabetic female rats. Endocrinology 111:1329–1333
Herington AC, Burger HG, Veith NM (1976) Binding of human growth hormone to hepatic lactogenic binding sites: regulation by oestrogens and androgens. J Endocrinol 70:473–484
Sherman BM, Stagner JI, Zamudio R (1977) Regulation of lactogenic hormone binding in rat liver by steroid hormones. Endocrinology 100:101–107
Kelly PA, Le Blanc G, Ferland L, Labrie F, De Lean A (1977) Androgen inhibition of basal and estrogen-stimulated prolactin binding in rat liver. Mol Cell Endocrinol 9:195–204
Aragona C, Bohnet HG, Friesen HG (1976) Prolactin binding sites in the male rat liver following castration. Endocrinology 99:1017–1022
Barkey RJ, Sham J, Zahav M, Amit T, Youdin MBH (1981) Effect of prolactin and prostaglandins on the stimulation of prolactin binding sites in the male rat liver. Mol Cell Endocrinol 21:129–138
Ranke MB, Stanley CA, Tenore A, Rodbard D, Bongiovanni AM, Parks JS (1976) Characterization of somatogenic and lactogenic binding sites in isolated rat hepatocytes. Endocrinology 99:1033–1045
Maes M, De Hertogh R, Watrin-Granger P and Ketelslegers JM (1983) Ontogeny of fiver somatotropic and lactogenic binding sites in male and female rats. Endocrinology 113:1325–1332
Baxter RC, Turtle JR (1978) Regulation of hepatic growth hormone receptors by insulin. Biochem Biophys Res Commun 84:350–357
Posner BI, Patel B, Vezinhet A and Charrier J (1980) Pituitary-dependent growth hormone receptors in rabbit and sheep liver. Endocrinology 107:1954–1958
Daughaday WH, Mariz IK, Blethen SL (1980) Inhibition of access of bound somatomedin to membrane receptor and immunobinding site: a comparison of radioreceptor and radioimmunoassay of somatomedin in native and acid-ethanol extracted serum. J Clin Endocrinol Metab 51:781–788
Baxter RC, Zaltsman Z, Oliver JR, Willoughby JO (1983) Pulsatility of immunoreactive somatomedin-C in chronically cannulated rats. Endocrinology 113:729–734
Braning JL, Kintz BL (1968) Computational handbook of statistics. Scott, Foresman, Glenview, Illinois, p 115
L'Age M, Langholz J, Fechner W, Salzmann H (1974) Disturbances of the hypothalamo-hypophysical-adrenocorticol system in the alloxan diabetic rat. Endocrinology 95:760–765
De Nicola AF, Fridman O, Del Castillo EJ, Foglia VG (1977) Abnormal regulation of adrenal function in rats with streptozotocin diabetes. Horm Metab Res 9:469–473
Baxter RC, Bryson JM, Turtle JR (1981) The effect of fasting on liver receptors for prolactin and growth hormone. Metabolism 30:1086–1090
Tannenbaum GS, Epelbaum J, Colle E, Brazeau P, Martin J (1978) Antiserum to somatostatin reverses starvation-induced inhibition of growth hormone but not insulin secretion. Endocrinology 102:1909–1914
Tannenbaum GS (1981) Growth hormone secretory dynamics in streptozotocin diabetes. Evidence for a role for endogenous circulating somatostatin. Endocrinology 108:76–82
Maes M, Underwood LE, Ketelslegers J-M (1983) Plasma somatomedin-C in fasted and refed rats: close relationship with changes in liver somatogenic but not lactogenic binding sites. J Endocrinol 97:243–252
Chihara K, Minamitani N, Kagi H, Kodama H, Kita T, Fujita T (1984) Noradrenergic modulation of human pancreatic growth hormone-releasing factor (hpGHRF 1-44)-induced growth hormone release in conscious male rabbits: Involvement of endogenous somatostatin. Endocrinology 114:1402–1406
Norstedt G (1982) A comparison between the effects of growth hormone on prolactin receptors and estrogen receptors in rat liver. Endocrinology 110:2107–2112
Baxter RC, Zaltsman Z, Turtle JR (1984) Rat growth hormone, but not prolactin, induces both growth hormone and prolactin receptors in female rat liver. Endocrinology 114:1893–1901
Baxter RC, Zaltsman Z (1984) Induction of hepatic receptors for growth hormone (GH) and prolactin by GH infusion is sex independent. Endocrinology 115:1009–1014
Daughaday WH, Heins JN, Srivastava L, Hammer C (1968) Sulfation factor: Studies of its removal from plasma and metabolic fate in cartilage. J Lab Clin Med 72:803–812
Scott CD, Martin JL, Baxter RC (1985) Rat hepatocyte insulin-like growth factor I and binding protein: Effect of growth hormone in vitro and in vivo. Endocrinology 116:1102–1107
Tannenbaum GS, Martin JB (1976) Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology 98:562–570
Terry LC, Saunders A, Audet J, Willoughby JO, Brazeau P, Martin JB (1977) Physiologic secretion of growth hormone and prolactin in male and female rats. Clin Endocrinol 6:19s-28s
Takahashi K, Daughaday WH, Kipnis DM (1971) Regulation of immunoreative growth hormone secretion in male rats. Endocrinology 88:909–917
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bryson, J.M., Baxter, R.C. Adrenal involvement in the diabetes-induced loss of growth hormone and prolactin receptors in the livers of female rats. Diabetologia 29, 106–111 (1986). https://doi.org/10.1007/BF00456119
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00456119