Identification of stimulatory and inhibitory inputs to the hypothalamic-pituitary-adrenal axis during hypoglycaemia or transport in Ewes

Robert F. Smith, N. P. French, P. W. Saphier, P. J. Lowry, Johannes D Veldhuis, H. Dobson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

This study used the novel approach of statistical modelling to investigate the control of hypothalamic-pituitary-adrenal (HPA) axis and quantify temporal relationships between hormones. Two experimental paradigms were chosen, insulin-induced hypoglycaemia and 2 h transport, to assess differences in control between noncognitive and cognitive stimuli. Vasopressin and corticotropin-releasing hormone (CRH) were measured in hypophysial portal plasma, and adrenocorticotropin hormone (ACTH) and cortisol in jugular plasma of conscious sheep, and deconvolution analysis was used to calculate secretory rates, before modelling. During hypoglycaemia, the relationship between plasma glucose and vasopressin or CRH was best described by log10 transforming variables (i.e. a positive power-curve relationship). A negative-feedback relationship with log10 cortisol concentration 2 h previously was detected. Analysis of the 'transport' stimulus suggested that the strength of the perceived stimulus decreased over time after accounting for cortisol facilitation and negative-feedback. The time course of vasopressin and CRH responses to each stimulus were different However, at the pituitary level, the data suggested that log10 ACTH secretion rate was related to log10 vasopressin and CRH concentrations with very similar regression coefficients and an identical ratio of actions (2.3 : 1) for both stimuli. Similar magnitude negative-feedback effects of log10 cortisol at - 110 min (hypoglycaemia) or -40 min (transport) were detected, and both models contained a stimulatory relationship with cortisol at 0 min (facilitation). At adrenal gland level, cortisol secretory rates were related to simultaneously measured untransformed ACTH concentration but the regression coefficient for the hypoglycaemia model was 2.5-fold greater than for transport. No individual sustained maximum cortisol secretion for longer than 20 min during hypoglycaemia and 40 min during transport. These unique models demonstrate that corticosteroid negative-feedback is a significant control mechanism at both the pituitary and hypothalamus. The amplitude of HPA response may be related to stimulus intensity and corticosteroid negative-feedback, while duration depended on feedback alone.

Original languageEnglish (US)
Pages (from-to)572-585
Number of pages14
JournalJournal of Neuroendocrinology
Volume15
Issue number6
StatePublished - Jun 1 2003

Fingerprint

Hypoglycemia
Hydrocortisone
Corticotropin-Releasing Hormone
Vasopressins
Secretory Rate
Hormones
Adrenocorticotropic Hormone
Adrenal Cortex Hormones
Adrenal Glands
Hypothalamus
Sheep
Neck
Insulin
Glucose

Keywords

  • ACTH
  • AVP
  • Cortisol
  • CRH
  • Stress
  • Vasopressin

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)

Cite this

Smith, R. F., French, N. P., Saphier, P. W., Lowry, P. J., Veldhuis, J. D., & Dobson, H. (2003). Identification of stimulatory and inhibitory inputs to the hypothalamic-pituitary-adrenal axis during hypoglycaemia or transport in Ewes. Journal of Neuroendocrinology, 15(6), 572-585.

Identification of stimulatory and inhibitory inputs to the hypothalamic-pituitary-adrenal axis during hypoglycaemia or transport in Ewes. / Smith, Robert F.; French, N. P.; Saphier, P. W.; Lowry, P. J.; Veldhuis, Johannes D; Dobson, H.

In: Journal of Neuroendocrinology, Vol. 15, No. 6, 01.06.2003, p. 572-585.

Research output: Contribution to journalArticle

Smith, RF, French, NP, Saphier, PW, Lowry, PJ, Veldhuis, JD & Dobson, H 2003, 'Identification of stimulatory and inhibitory inputs to the hypothalamic-pituitary-adrenal axis during hypoglycaemia or transport in Ewes', Journal of Neuroendocrinology, vol. 15, no. 6, pp. 572-585.
Smith, Robert F. ; French, N. P. ; Saphier, P. W. ; Lowry, P. J. ; Veldhuis, Johannes D ; Dobson, H. / Identification of stimulatory and inhibitory inputs to the hypothalamic-pituitary-adrenal axis during hypoglycaemia or transport in Ewes. In: Journal of Neuroendocrinology. 2003 ; Vol. 15, No. 6. pp. 572-585.
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