The acute effect of lowering plasma cortisol on the secretion of corticotropin-releasing hormone, arginine vasopressin, and adrenocorticotropin as revealed by intensive sampling of pituitary venous blood in the normal horse.
Abstract: The effect of an acute fall in plasma cortisol on the secretion of CRH, arginine vasopressin (AVP), and ACTH was studied using our nonsurgical technique for collecting pituitary venous (PV) blood from horses. PV blood from six mares was collected continuously and divided into 30-sec segments for 0.5 h before and during a 3-h infusion of metyrapone, an 11-beta-hydroxylase inhibitor. During treatment, plasma cortisol fell (P < 0.01) to a mean nadir of 15% of pretreatment levels, and 11-deoxy-cortisol rose (P < 0.02). Three mares became mildly agitated during treatment. Mean PV concentrations of CRH (P < 0.025), AVP (P < 0.05), and ACTH (P < 0.005) were higher during the second hour of treatment than before. For AVP (P < 0.05) and ACTH (P < 0.01), the amount secreted in peaks detected by CLUSTER analysis increased during treatment, whereas peak frequency did not. Responses, particularly in CRH and AVP, tended to be amplified during agitation. Increases in CRH, AVP, and ACTH secretion commenced when cortisol had fallen to 50-59% of the initial value (P < 0.005 for each). By contrast, the cortisol concentration at this point varied 3-fold among mares. The ratio between PV concentrations of ACTH and CRH, which was used as an index of pituitary responsiveness to endogenous CRH, also rose (P < 0.005) as cortisol fell. The increase in this ratio preceded any significant change in CRH secretion and was maintained to the end of the experiment. We suggest that the initial response to falling cortisol in the horse is at the pituitary, via increased responsiveness to CRH. If cortisol continues to fall, AVP and then CRH secretion are stimulated. However, the magnitude of the hypothalamic response to hypocortisolemia may be augmented by concurrent stress. Last, the hypothalamo-pituitary-adrenal axis of the horse appears to monitor changes in plasma cortisol and not concentrations, at least in the short term.
Publication Date: 1993-08-01 PubMed ID: 8393777DOI: 10.1210/endo.133.2.8393777Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- P.H.S.
Summary
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The research investigates the physiological consequences of a sudden drop in plasma cortisol levels on the secretion of other hormones — corticotropin-releasing hormone (CRH), arginine vasopressin (AVP), and adrenocorticotropin (ACTH) — in horses. The study revealed that diminishing cortisol levels triggered an increase in the secretion of CRH, AVP, and ACTH, suggesting an interlink between these hormones and how their alteration impacts the horse’s body functions and stress response.
Methodology
- The study was conducted on six mares using a non-surgical technique for pituitary venous (PV) blood collection.
- PV blood was gathered and divided into 30-second segments for half an hour prior to and during a 3-hour infusion with metyrapone, an 11-beta-hydroxylase inhibitor.
- Metyrapone was used to induce a sudden fall in plasma cortisol levels.
- Blood hormone concentrations were analyzed using CLUSTER statistical analysis.
Findings
- Dropping the levels of cortisol resulted in an increased secretion of CRH, AVP, and ACTH, however, the peak frequency of secretion did not change.
- Interestingly, the researchers observed that the onset of increased hormone secretion (CRH, AVP, ACTH) started when cortisol levels had dropped to 50-59% of the initial value.
- The ratio of ACTH to CRH (demonstrating pituitary responsiveness to CRH) also increased as cortisol levels decreased.
- Three of the mares became mildly agitated during the treatment, suggesting a link between the dropping cortisol level and stress.
Conclusions
- According to the study, the first reaction to falling cortisol in horses is an increased responsiveness to CRH at the pituitary gland.
- If cortisol continues to decrease, AVP and then CRH secretion are stimulated. However, this response can be magnified under stressful conditions.
- The findings suggest that the hypothalamo-pituitary-adrenal axis in horses appears to monitor changes in plasma cortisol levels rather than absolute concentrations – at least in the short term.
- This research sheds light on the intricate inter-hormonal regulatory processes that maintain physiological homeostasis in horses.
Cite This Article
APA
Alexander SL, Irvine CH, Livesey JH, Donald RA.
(1993).
The acute effect of lowering plasma cortisol on the secretion of corticotropin-releasing hormone, arginine vasopressin, and adrenocorticotropin as revealed by intensive sampling of pituitary venous blood in the normal horse.
Endocrinology, 133(2), 860-866.
https://doi.org/10.1210/endo.133.2.8393777 Publication
Researcher Affiliations
- Department of Endocrinology, Christchurch Public Hospital, New Zealand.
MeSH Terms
- Adrenocorticotropic Hormone / blood
- Adrenocorticotropic Hormone / metabolism
- Animals
- Arginine Vasopressin / blood
- Arginine Vasopressin / metabolism
- Corticotropin-Releasing Hormone / blood
- Corticotropin-Releasing Hormone / metabolism
- Female
- Horses / blood
- Hydrocortisone / blood
- Kinetics
- Metyrapone / pharmacology
- Pituitary Gland / blood supply
- Veins
Grant Funding
- DK38322 / NIDDK NIH HHS
Citations
This article has been cited 3 times.- Keenan DM, Alexander S, Irvine C, Veldhuis JD. Quantifying nonlinear interactions within the hypothalamo-pituitary-adrenal axis in the conscious horse.. Endocrinology 2009 Apr;150(4):1941-51.
- Lujan ME, MacTavish PJ, Krzemien AA, Bradstock MW, Van Vugt DA. Estrogen-induced gonadotropin surge in rhesus monkeys is not inhibited by cortisol synthesis inhibition or hypoglycemia.. Endocrine 2002 Nov;19(2):169-76.
- Holmes SJ, Florkowski CM, Evans MJ, Ellis MJ, Livesey JH, Donald RA, Espiner EA. Metyrapone induced increase in plasma corticotropin is not associated with changes in peripheral venous arginine vasopressin or corticotropin releasing factor.. J Endocrinol Invest 1993 Nov;16(10):787-92.
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