Hypophysiotropic regulation of adrenocorticotropin secretion in response to insulin-induced hypoglycemia.

The hypophysiotropic coding of ACTH secretion resulting from insulin-induced hypoglycemia was investigated in urethane-anesthetized fasted rats. The participation of corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and catecholamines in the ACTH response was first investigated by systemic administration of CRF antiserum, an AVP pressor antagonist, or a ganglionic blocking agent. These treatments were without effect on the hypoglycemic response, which was characterized by a 67% fall in systemic glucose levels within 30 min of insulin administration. ACTH secretion in response to insulin-induced hypoglycemia was differentially affected by these pharmacological treatments. Administration of antiserum to CRF abolished the ACTH response, whereas ganglionic blockade was without significant effect. However, administration of a vasopressinergic pressor antagonist significantly attenuated ACTH secretion after insulin treatment. These observations suggested the participation of both CRF and AVP in mediation of the ACTH secretory response to hypoglycemia. Infusion of glucose to counter the hypoglycemia action of insulin injection prevented the ACTH secretory response. Measurement of immunoreactive (ir) CRF, irAVP, and ir-oxytocin in sequential collections of hypophysial portal plasma revealed a significant elevation of irAVP concentration without concomitant elevation of irCRF or ir-oxytocin levels. We propose that CRF functions in a permissive role, maintaining a relatively constant portal concentration and thereby allowing expression of the weaker ACTH-releasing activity of AVP and other secretagogues. Thus, AVP, not CRF, appears to represent the dynamic mediator of ACTH secretion accompanying insulin-induced hypoglycemia. These observations provide additional support for the hypothesis of multifactor stimulus-specific hypophysiotropic coding of ACTH secretion.

[1]  D. Gibbs.  Inhibition of corticotropin release during hypothermia: the role of corticotropin-releasing factor, vasopressin, and oxytocin. , 1985, Endocrinology.

[2]  P. Plotsky,et al.  Evidence for multifactor regulation of the adrenocorticotropin secretory response to hemodynamic stimuli. , 1985, Endocrinology.

[3]  M. Palkovits,et al.  Beta-adrenergic mechanism of insulin-induced adrenocorticotropin release from the anterior pituitary. , 1984, Science.

[4]  F. Antoni.  Novel ligand specificity of pituitary vasopressin receptors in the rat. , 1984, Neuroendocrinology.

[5]  Y. Oomura,et al.  Glucose responding neurons in the nucleus tractus solitarius of the rat: In vitro study , 1984, Brain Research.

[6]  D. Gibbs.  High concentrations of oxytocin in hypophysial portal plasma. , 1984, Endocrinology.

[7]  W. Vale,et al.  Modulation of stress-induced ACTH release by corticotropin-releasing factor, catecholamines and vasopressin , 1983, Nature.

[8]  W. Vale,et al.  Interaction of corticotropin-releasing factor and arginine vasopressin on adrenocorticotropin secretion in vivo. , 1983, Endocrinology.

[9]  J. Vaughan,et al.  Effects of synthetic ovine corticotropin-releasing factor, glucocorticoids, catecholamines, neurohypophysial peptides, and other substances on cultured corticotropic cells. , 1983, Endocrinology.

[10]  A. Negro-Vilar,et al.  High concentrations of epinephrine derived from a central source and of 5-hydroxyindole-3-acetic acid in hypophysial portal plasma. , 1983, Endocrinology.

[11]  M. Dallman,et al.  Inhibition of the adrenocorticotropin and corticosteroid responses to hypoglycemia after prior stress. , 1983, Endocrinology.

[12]  M. Vlaskovska,et al.  In vitro CRF activity of vasopressin analogs is not related to pressor activity. , 1983, European journal of pharmacology.

[13]  M. Holmes,et al.  Oxytocin as well as vasopressin potentiate ovine CRF in vitro , 1983, Peptides.

[14]  Y. Oomura,et al.  Functional correlations between lateral hypothalamic glucose-sensitive neurons and hepatic portal glucose-sensitive units in rat , 1983, Brain Research.

[15]  C. Wade,et al.  Insulin-induced hypoglycemia in conscious dogs: effect of maintaining carotid arterial glucose levels on the adrenocorticotropin, epinephrine, and vasopressin responses. , 1983, Endocrinology.

[16]  V. Giguère,et al.  Additive effects of epinephrine and corticotropin-releasing factor (CRF) on adrenocorticotropin release in rat anterior pituitary cells. , 1983, Biochemical and biophysical research communications.

[17]  P. Plotsky,et al.  The decrease in hypothalamic dopamine secretion induced by suckling: comparison of voltammetric and radioisotopic methods of measurement. , 1982, Endocrinology.

[18]  M. Greer,et al.  Hypoglycemia stimulates ACTH secretion through a direct effect on the basal hypothalamus. , 1981, Metabolism: clinical and experimental.

[19]  W. Vale,et al.  Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin , 1981 .

[20]  M. Dallman,et al.  Insulin-induced hypoglycemia in conscious dogs. I. Dose-related pituitary and adrenal responses. , 1981, Endocrinology.

[21]  L. Recht,et al.  Vasopressin concentrations in hypophysial portal plasma: insignificant reduction following removal of the posterior pituitary gland. , 1981, Neuroendocrinology.

[22]  R. Ritter,et al.  Glucoreceptors controlling feeding and blood glucose: location in the hindbrain. , 1981, Science.

[23]  G. Robertson,et al.  Rat vasopressin response to insulin-induced hypoglycemia. , 1980, Endocrinology.

[24]  D. Fisher,et al.  Somatostatin analog: plasma catecholamine suppression mediated by the central nervous system. , 1980, Endocrinology.

[25]  L. Keil,et al.  Thirst and vasopressin release in the dog: an osmoreceptor or sodium receptor mechanism? , 1980, The American journal of physiology.

[26]  R. Weitzman,et al.  The effect of hemorrhage and hypertonic saline upon plasma oxytocin and arginine vasopressin in conscious dogs. , 1978, Endocrinology.

[27]  M. Manning,et al.  Design of potent antagonists of the vasopressor response to arginine-vasopressin. , 1978, Journal of medicinal chemistry.

[28]  R. Donald,et al.  The plasma cortisol and corticotropin response to hypoglycemia following adrenal steroid and ACTH administration. , 1975, Journal of Clinical Endocrinology and Metabolism.

[29]  J. Plager,et al.  Rate of blood glucose fall as a determinant factor in insulin-induced adrenocortical stimulation. , 1966, Endocrinology.

[30]  Seymour Geisser,et al.  Statistical Principles in Experimental Design , 1963 .

[31]  V. Wynn,et al.  THE ADRENOCORTICAL RESPONSE TO INSULIN-INDUCED HYPOGLYCAEMIA. , 1963, The Journal of endocrinology.

[32]  G. Sayers,et al.  Content of adrenocorticotropic hormone in the rat pituitary under optimal and stressful environmental conditions. , 1948, Journal of Clinical Endocrinology and Metabolism.

[33]  P. Plotsky,et al.  Hemorrhage-induced secretion of corticotropin-releasing factor-like immunoreactivity into the rat hypophysial portal circulation and its inhibition by glucocorticoids. , 1984, Endocrinology.

[34]  J. Vaughan,et al.  [38] Assay of corticotropin releasing factor , 1983 .

[35]  F. Tilders,et al.  Adrenergic mechanisms involved in the control of pituitary-adrenal activity in the rat: a beta-adrenergic stimulatory mechanism. , 1982, Endocrinology.

[36]  M. Greer,et al.  In vivo adrenocorticotropin-releasing activity of neurohypophyseal hormones and their analogs. , 1982, Endocrinology.