The Hypothalamic Pituitary Adrenal (HPA) Axis in horses is a complex neuroendocrine system that plays a significant role in regulating stress responses, metabolism, and immune function. It involves interactions between the hypothalamus, pituitary gland, and adrenal glands. Upon perceiving stress, the hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to secrete adrenocorticotropic hormone (ACTH). ACTH then prompts the adrenal glands to produce cortisol, a hormone that helps manage stress and modulate various physiological processes. The HPA axis is subject to regulation and feedback mechanisms to maintain homeostasis. This page compiles peer-reviewed research studies and scholarly articles that explore the function, regulation, and implications of the HPA axis in equine physiology and health.
This study aimed to evaluate the change of white blood cell count, serum concentration of cortisol, C-reactive protein, albumin and globulin fractions in horse after road transport, and to assess the linkage among hypothalamic-pituitary-adrenal axis (HPA) and inflammatory reaction. From 10 horses blood samples were collected at rest, before road transport (218 km) (BT); after unloaded (AT), 30 and 60 min after unloaded (AT30 and AT60) in order to assess white blood cell count (WBC), serum cortisol, C-reactive protein (CRP), total proteins, albumin, α1-, α-2, β1-, β2- and γ-globulins. WB...
Holyoak GR, Ma A.Historical evidence of acupuncture predates written history. It has been a component of Traditional Chinese veterinary medicine for many generations and is officially recognized in recorded history for treating equine disease in the Zhou Dynasty, circa 1050 BC. Drawing from a range of searchable databases, we present the use of veterinary acupuncture related to theriogenology. We touch on human-based medicine only as an introduction to current uses within veterinary medical acupuncture. This review is confined to the use of acupuncture encompassing dry needle, electroacupuncture, aquapuncture,...
Olvera-Maneu S, Carbajal A, Gardela J, Lopez-Bejar M.The monitoring of stress physiology includes studying a wide range of endocrinological mechanisms, which can be assessed using multiple tissue samples. This study aimed to evaluate the seasonal variations of hair C, T and DHEA-S in horses for a whole year, as well as to assess the variations between seasons of C/DHEA-S and T/C ratios as a retrospective measure of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axis activity. Ten pure-breed Menorca stallions were included in the study. The hair samples were collected approximately every two months following the shave-resha...
Sauer FJ, Gerber V, Frei S, Bruckmaier RM, Groessl M.The aim of the present study was to measure salivary cortisol concentrations of horses before and after hypothalamic-pituitary-adrenal (HPA) axis stimulation by means of liquid chromatography-tandem-mass spectrometry (LC-MS/MS) and an immunoassay (cELISA) for method comparison. Nine clinically healthy horses participated in the study. An ACTH stimulation test was performed. Saliva samples were collected before (T0) and 60 (T60) min after intravenous injection of 1 μg/kg BW synthetic ACTH1-24. LC-MS/MS was assessed for the determination of equine salivary cortisol. The results of these measur...
Banse HE, Getachew F, Levy M, Smits J.Hair cortisol has been demonstrated to reflect hypothalamic-pituitary-adrenal axis activity (including Cushing's disease and stress) in several species. We hypothesized that hair cortisol concentrations are increased in horses with pituitary pars intermedia dysfunction (PPID) compared with healthy adult horses and that this difference is magnified in the fall, when circulating adrenocorticotropin (ACTH) is generally the highest. Cortisol from hair collected using clippers with a #40 blade from the neck was compared between PPID horses and control horses over several months in the fall (August-...
Pohlin F, Brabender K, Fluch G, Stalder G, Petit T, Walzer C. Ecosystems with seasonal fluctuations in climate and food availability present physiological challenges to resident mammals and may cause "stress." The two predominant physiological responses to stressors are (1) the activation of the hypothalamic-pituitary-adrenal axis and (2) the modulation of the autonomic nervous system. To date, the primary indicator for "stress" in wildlife- and zoo animal research are glucocorticoid levels. By measuring the autonomic regulation of cardiac activity, particularly the vagal tone, heart rate variability (HRV) is presently emerging as a suitable indicator o...
Haspel AD, Giguère S, Hart KA, Berghaus LJ, Davis JL.Nebulisation of the injectable dexamethasone sodium phosphate (DSP) would offer an inexpensive way of delivering a potent corticosteroid directly to the lungs of horses with asthma. However, this approach would be advantageous only if systemic absorption is minimal and if the preservatives present in the formulation do not induce airway inflammation. Objective: To investigate the bioavailability of nebulised DSP and determine whether it induces airway inflammation or hypothalamic-pituitary-adrenal (HPA) axis suppression in healthy adult horses. Methods: Randomised crossover experiment. Methods...
Dembek KA, Timko KJ, Johnson LM, Hart KA, Barr BS, David B, Burns TA, Toribio RE.Hypothalamic-pituitary-adrenal axis (HPAA) dysfunction has been associated with sepsis and mortality in foals. Most studies have focused on cortisol, while other steroids have not been investigated. The objectives of this study were to characterise the adrenal steroid and steroid precursor response to disease and to determine their association with the HPAA response to illness, disease severity, and mortality in hospitalised foals. All foals (n=326) were classified by two scoring systems into three categories: based on the sepsis score (septic, sick non-septic [SNS] and healthy) and the foal s...
Fazio E, Medica P, Cravana C, Ferlazzo AA.The changes of the hypothalamic pituitary adrenal (HPA) axis response to a long distance transportation results in increase of adrenocorticotropic hormone (ACTH) and cortisol levels. The purpose of the study was to quantify the level of short-term road transport stress on circulating ACTH and cortisol concentrations, related to the effect of previous handling and transport experience of horses. Methods: The study was performed on 56 healthy horses after short-term road transport of 30 km. The horses were divided into four groups, Groups A, B, C, and D, with respect to the handling quality: Goo...
Bertin FR, Pader KS, Lescun TB, Sojka-Kritchevsky JE.To evaluate the effect of ovariectomy on insulin sensitivity in horses and determine whether the effects of suppression of the hypothalamo-pituitary-adrenal axis differ before and after ovariectomy. Methods: 6 healthy mares. Methods: The horses underwent an IV glucose tolerance test (IVGTT), an insulin sensitivity test, and a dexamethasone suppression test before and 5 weeks after ovariectomy. Body weight, serum cortisol and plasma ACTH concentrations, serum insulin-to-blood glucose concentration ratios, and changes in blood glucose concentration with time after injection of glucose or insulin...
Fazio E, Medica P, Cravana C, Ferlazzo A.In order to determine whether therapeutic riding could result in higher levels of stress than recreational riding, hypothalamic-pituitary-adrenal (HPA) axis response was evaluated in six horses by monitoring circulating β-endorphin, ACTH and cortisol concentrations. Horses were already accustomed to be trained both for therapy and riding school activity since 2004. Intervention consisted of 60-minute therapeutic sessions, two times per week for 6weeks with different riders: disabled and recreational riders (session A and B respectively). The therapeutic riders' group (A) consisted of six chil...
Capolongo F, Gallina G, Fidani M, Baia F, Montesissa C.This study investigated whether a single intra-articular administration (IA) of dexamethasone (DEX) in horses at therapeutic dosage could exert a systemic effect by influencing the hypothalamic-pituitary-adrenal axis activity as a consequence of (limited) absorption and systemic distribution. The results indicated that DEX was detectable in urine collected 12-48 h after IA administration and that injection was accompanied by a reduced urine excretion of cortisol, 6β-hydroxycortisol (6βOHF) and two other metabolites of cortisol lasting up to 48 h post-DEX administration. The systemic effect...
Himler M, Hurcombe SD, Griffin A, Barsnick RJ, Rathgeber RA, MacGillivray KC, Toribio RE.Hypothalamic-pituitary-thyroid (HPT) axis dysfunction is associated with morbidity and mortality in critically ill people. To date, investigations of HPT axis in critically ill foals are limited. Objective: To document the occurrence of low thyroid hormone concentrations (presumptive nonthyroidal illness syndrome; NTIS) in critically ill newborn foals and investigate whether NTIS is associated with severity of disease and outcome. Objective: NTIS occurs frequently in foals with sepsis and is associated with sepsis score and outcome. Reverse T3 (rT3) concentrations will be increased in septic f...
Jellyman JK, Allen VL, Forhead AJ, Holdstock NB, Fowden AL.The effects of overexposure to glucocorticoids during early life of the foal on the subsequent HPA programming of the hypothalamic-pituitary-adrenal axis are unknown. Objective: To test the hypotheses that excess glucocorticoid exposure in early life subsequently increases both basal plasma concentrations of cortisol and the adrenocortical responsiveness to exogenous adrenocorticotropic hormone (ACTH). Methods: Foals received either saline (0.9% NaCl, n = 9) or long-acting ACTH (0.125 mg i.m. b.i.d., n = 6) for 5 days from Day 1 to increase endogenous cortisol concentrations. Long-term indwell...
Franco C, Paris JJ, Wulfert E, Frye CA.Prevalence rates of gambling are influenced by gender. Among normative populations, hypothalamic-pituitary-adrenal (HPA) axis response to stress is affected by gender. However, pathological, compared to recreational, gamblers demonstrate perturbations in HPA activation in response to gambling stimuli. We examined whether there were gender differences in HPA response to gambling in a naturalistic setting among horse-race bettors and scratch-off lottery bettors. Salivary cortisol was collected from horse-race gamblers (n=32) and scratch-off lottery ticket players (n=39) before and after (0, 10, ...
Hart KA, Heusner GL, Norton NA, Barton MH.Hypothalamic-pituitary-adrenal (HPA) axis function is dynamic in the neonatal foal. The paired low dose/high dose cosyntropin (ACTH) stimulation test allows comprehensive HPA axis assessment, but has not been evaluated in neonatal foals. Objective: Foal age will significantly affect cortisol responses to a paired 10 and 100 microg dose cosyntropin stimulation test in healthy neonatal foals. Methods: Twenty healthy neonatal foals. Methods: HPA axis function was assessed in 12 foals at birth and at 12-24, 36-48 hours, and 5-7 days of age. At each age, basal cortisol and ACTH concentrations were ...
Luna SP, Taylor PM.Halothane depresses cardiorespiratory function and activates the pituitary-adrenal axis, increasing beta endorphin. In horses, beta endorphin may enhance the anaesthetic-associated cardiorespiratory depression and mortality risk. The authors studied endogenous opioid effects on cardiorespiratory function and pituitary-adrenal activity in halothane-anaesthetised ponies by investigating opioid antagonism by naloxone. Six ponies were anaesthetised three times (crossover design). Anaesthesia was induced with thiopentone and maintained with 1.2 per cent halothane for 2 hours. Immediately after indu...
Nagata S, Takeda F, Kurosawa M, Mima K, Hiraga A, Kai M, Taya K.The responses of plasma adrenocorticotropin (ACTH), cortisol, noradrenaline and adrenaline in 5 Thoroughbred horses to an incremental exercise and 2 relative workload exercises, at 105 and 80% maximal oxygen consumption (VO2max), on a treadmill were examined. These hormone concentrations increased (P < 0.05) with each exercise and the maximal plasma concentrations of ACTH, cortisol were observed between 5 and 30 min after the end of the exercise, while maximal catecholamine concentrations occurred just at exhaustion time. The plasma ACTH, noradrenaline and adrenaline responses during exerci...
Alexander SL, Irvine CH, Donald RA.Since 1985, we have applied our nonsurgical technique for collecting pituitary venous (PitVen) blood from ambulatory horses to investigate the regulation of adrenocorticotropic hormone (ACTH) secretion. This method offers particular advantages for studying the hypothalamo-pituitary-adrenal axis since its benign nature enables hypothalamic and pituitary interactions to be monitored without disturbing the animal, and the horse's large blood volume allows 3- to 4-ml samples to be collected as frequently as every 20s for prolonged periods so that the secretion patterns of ACTH and its secretagogue...
Sharp DC, Grubaugh W, Berglund LA, McDowell KJ, Kilmer DM, Peck LS, Seamans KW, Chen CL.The pituitary stalk was transected in 10 Pony mares by a surgical approach that involved dorsal reflection of the brain and micro-dissection from the ventro-lateral aspect of the pituitary. Diabetes insipidus was the most immediate and marked result, requiring extensive electrolyte and antidiuretic therapy for approximately 48 h after operation. Fluid stasis then developed and no further supportive measures were necessary. Endocrine challenge tests with GnRH and TRH before and after stalk transection indicated a loss of responsiveness (GnRH) or suppressed responsiveness (TRH) after the operati...
Dembek KA, Timko KJ, Johnson LM, Hart KA, Barr BS, David B, Burns TA, Toribio RE.Hypothalamic-pituitary-adrenal axis (HPAA) dysfunction has been associated with sepsis and mortality in foals. Most studies have focused on cortisol, while other steroids have not been investigated. The objectives of this study were to characterise the adrenal steroid and steroid precursor response to disease and to determine their association with the HPAA response to illness, disease severity, and mortality in hospitalised foals. All foals (n=326) were classified by two scoring systems into three categories: based on the sepsis score (septic, sick non-septic [SNS] and healthy) and the foal s...
Fazio E, Medica P, Cravana C, Ferlazzo A.In order to determine whether therapeutic riding could result in higher levels of stress than recreational riding, hypothalamic-pituitary-adrenal (HPA) axis response was evaluated in six horses by monitoring circulating β-endorphin, ACTH and cortisol concentrations. Horses were already accustomed to be trained both for therapy and riding school activity since 2004. Intervention consisted of 60-minute therapeutic sessions, two times per week for 6weeks with different riders: disabled and recreational riders (session A and B respectively). The therapeutic riders' group (A) consisted of six chil...
Nagata S, Takeda F, Kurosawa M, Mima K, Hiraga A, Kai M, Taya K.The responses of plasma adrenocorticotropin (ACTH), cortisol, noradrenaline and adrenaline in 5 Thoroughbred horses to an incremental exercise and 2 relative workload exercises, at 105 and 80% maximal oxygen consumption (VO2max), on a treadmill were examined. These hormone concentrations increased (P < 0.05) with each exercise and the maximal plasma concentrations of ACTH, cortisol were observed between 5 and 30 min after the end of the exercise, while maximal catecholamine concentrations occurred just at exhaustion time. The plasma ACTH, noradrenaline and adrenaline responses during exerci...
Sauer FJ, Gerber V, Frei S, Bruckmaier RM, Groessl M.The aim of the present study was to measure salivary cortisol concentrations of horses before and after hypothalamic-pituitary-adrenal (HPA) axis stimulation by means of liquid chromatography-tandem-mass spectrometry (LC-MS/MS) and an immunoassay (cELISA) for method comparison. Nine clinically healthy horses participated in the study. An ACTH stimulation test was performed. Saliva samples were collected before (T0) and 60 (T60) min after intravenous injection of 1 μg/kg BW synthetic ACTH1-24. LC-MS/MS was assessed for the determination of equine salivary cortisol. The results of these measur...
Pohlin F, Brabender K, Fluch G, Stalder G, Petit T, Walzer C. Ecosystems with seasonal fluctuations in climate and food availability present physiological challenges to resident mammals and may cause "stress." The two predominant physiological responses to stressors are (1) the activation of the hypothalamic-pituitary-adrenal axis and (2) the modulation of the autonomic nervous system. To date, the primary indicator for "stress" in wildlife- and zoo animal research are glucocorticoid levels. By measuring the autonomic regulation of cardiac activity, particularly the vagal tone, heart rate variability (HRV) is presently emerging as a suitable indicator o...
Fazio E, Medica P, Cravana C, Ferlazzo AA.The changes of the hypothalamic pituitary adrenal (HPA) axis response to a long distance transportation results in increase of adrenocorticotropic hormone (ACTH) and cortisol levels. The purpose of the study was to quantify the level of short-term road transport stress on circulating ACTH and cortisol concentrations, related to the effect of previous handling and transport experience of horses. Methods: The study was performed on 56 healthy horses after short-term road transport of 30 km. The horses were divided into four groups, Groups A, B, C, and D, with respect to the handling quality: Goo...
Haspel AD, Giguère S, Hart KA, Berghaus LJ, Davis JL.Nebulisation of the injectable dexamethasone sodium phosphate (DSP) would offer an inexpensive way of delivering a potent corticosteroid directly to the lungs of horses with asthma. However, this approach would be advantageous only if systemic absorption is minimal and if the preservatives present in the formulation do not induce airway inflammation. Objective: To investigate the bioavailability of nebulised DSP and determine whether it induces airway inflammation or hypothalamic-pituitary-adrenal (HPA) axis suppression in healthy adult horses. Methods: Randomised crossover experiment. Methods...
Franco C, Paris JJ, Wulfert E, Frye CA.Prevalence rates of gambling are influenced by gender. Among normative populations, hypothalamic-pituitary-adrenal (HPA) axis response to stress is affected by gender. However, pathological, compared to recreational, gamblers demonstrate perturbations in HPA activation in response to gambling stimuli. We examined whether there were gender differences in HPA response to gambling in a naturalistic setting among horse-race bettors and scratch-off lottery bettors. Salivary cortisol was collected from horse-race gamblers (n=32) and scratch-off lottery ticket players (n=39) before and after (0, 10, ...
Himler M, Hurcombe SD, Griffin A, Barsnick RJ, Rathgeber RA, MacGillivray KC, Toribio RE.Hypothalamic-pituitary-thyroid (HPT) axis dysfunction is associated with morbidity and mortality in critically ill people. To date, investigations of HPT axis in critically ill foals are limited. Objective: To document the occurrence of low thyroid hormone concentrations (presumptive nonthyroidal illness syndrome; NTIS) in critically ill newborn foals and investigate whether NTIS is associated with severity of disease and outcome. Objective: NTIS occurs frequently in foals with sepsis and is associated with sepsis score and outcome. Reverse T3 (rT3) concentrations will be increased in septic f...
Banse HE, Getachew F, Levy M, Smits J.Hair cortisol has been demonstrated to reflect hypothalamic-pituitary-adrenal axis activity (including Cushing's disease and stress) in several species. We hypothesized that hair cortisol concentrations are increased in horses with pituitary pars intermedia dysfunction (PPID) compared with healthy adult horses and that this difference is magnified in the fall, when circulating adrenocorticotropin (ACTH) is generally the highest. Cortisol from hair collected using clippers with a #40 blade from the neck was compared between PPID horses and control horses over several months in the fall (August-...
Hart KA, Heusner GL, Norton NA, Barton MH.Hypothalamic-pituitary-adrenal (HPA) axis function is dynamic in the neonatal foal. The paired low dose/high dose cosyntropin (ACTH) stimulation test allows comprehensive HPA axis assessment, but has not been evaluated in neonatal foals. Objective: Foal age will significantly affect cortisol responses to a paired 10 and 100 microg dose cosyntropin stimulation test in healthy neonatal foals. Methods: Twenty healthy neonatal foals. Methods: HPA axis function was assessed in 12 foals at birth and at 12-24, 36-48 hours, and 5-7 days of age. At each age, basal cortisol and ACTH concentrations were ...
Alexander SL, Irvine CH, Donald RA.Since 1985, we have applied our nonsurgical technique for collecting pituitary venous (PitVen) blood from ambulatory horses to investigate the regulation of adrenocorticotropic hormone (ACTH) secretion. This method offers particular advantages for studying the hypothalamo-pituitary-adrenal axis since its benign nature enables hypothalamic and pituitary interactions to be monitored without disturbing the animal, and the horse's large blood volume allows 3- to 4-ml samples to be collected as frequently as every 20s for prolonged periods so that the secretion patterns of ACTH and its secretagogue...
Bertin FR, Pader KS, Lescun TB, Sojka-Kritchevsky JE.To evaluate the effect of ovariectomy on insulin sensitivity in horses and determine whether the effects of suppression of the hypothalamo-pituitary-adrenal axis differ before and after ovariectomy. Methods: 6 healthy mares. Methods: The horses underwent an IV glucose tolerance test (IVGTT), an insulin sensitivity test, and a dexamethasone suppression test before and 5 weeks after ovariectomy. Body weight, serum cortisol and plasma ACTH concentrations, serum insulin-to-blood glucose concentration ratios, and changes in blood glucose concentration with time after injection of glucose or insulin...
Olvera-Maneu S, Carbajal A, Gardela J, Lopez-Bejar M.The monitoring of stress physiology includes studying a wide range of endocrinological mechanisms, which can be assessed using multiple tissue samples. This study aimed to evaluate the seasonal variations of hair C, T and DHEA-S in horses for a whole year, as well as to assess the variations between seasons of C/DHEA-S and T/C ratios as a retrospective measure of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axis activity. Ten pure-breed Menorca stallions were included in the study. The hair samples were collected approximately every two months following the shave-resha...
Jellyman JK, Allen VL, Forhead AJ, Holdstock NB, Fowden AL.The effects of overexposure to glucocorticoids during early life of the foal on the subsequent HPA programming of the hypothalamic-pituitary-adrenal axis are unknown. Objective: To test the hypotheses that excess glucocorticoid exposure in early life subsequently increases both basal plasma concentrations of cortisol and the adrenocortical responsiveness to exogenous adrenocorticotropic hormone (ACTH). Methods: Foals received either saline (0.9% NaCl, n = 9) or long-acting ACTH (0.125 mg i.m. b.i.d., n = 6) for 5 days from Day 1 to increase endogenous cortisol concentrations. Long-term indwell...
Luna SP, Taylor PM.Halothane depresses cardiorespiratory function and activates the pituitary-adrenal axis, increasing beta endorphin. In horses, beta endorphin may enhance the anaesthetic-associated cardiorespiratory depression and mortality risk. The authors studied endogenous opioid effects on cardiorespiratory function and pituitary-adrenal activity in halothane-anaesthetised ponies by investigating opioid antagonism by naloxone. Six ponies were anaesthetised three times (crossover design). Anaesthesia was induced with thiopentone and maintained with 1.2 per cent halothane for 2 hours. Immediately after indu...
Capolongo F, Gallina G, Fidani M, Baia F, Montesissa C.This study investigated whether a single intra-articular administration (IA) of dexamethasone (DEX) in horses at therapeutic dosage could exert a systemic effect by influencing the hypothalamic-pituitary-adrenal axis activity as a consequence of (limited) absorption and systemic distribution. The results indicated that DEX was detectable in urine collected 12-48 h after IA administration and that injection was accompanied by a reduced urine excretion of cortisol, 6β-hydroxycortisol (6βOHF) and two other metabolites of cortisol lasting up to 48 h post-DEX administration. The systemic effect...
This study aimed to evaluate the change of white blood cell count, serum concentration of cortisol, C-reactive protein, albumin and globulin fractions in horse after road transport, and to assess the linkage among hypothalamic-pituitary-adrenal axis (HPA) and inflammatory reaction. From 10 horses blood samples were collected at rest, before road transport (218 km) (BT); after unloaded (AT), 30 and 60 min after unloaded (AT30 and AT60) in order to assess white blood cell count (WBC), serum cortisol, C-reactive protein (CRP), total proteins, albumin, α1-, α-2, β1-, β2- and γ-globulins. WB...
Sharp DC, Grubaugh W, Berglund LA, McDowell KJ, Kilmer DM, Peck LS, Seamans KW, Chen CL.The pituitary stalk was transected in 10 Pony mares by a surgical approach that involved dorsal reflection of the brain and micro-dissection from the ventro-lateral aspect of the pituitary. Diabetes insipidus was the most immediate and marked result, requiring extensive electrolyte and antidiuretic therapy for approximately 48 h after operation. Fluid stasis then developed and no further supportive measures were necessary. Endocrine challenge tests with GnRH and TRH before and after stalk transection indicated a loss of responsiveness (GnRH) or suppressed responsiveness (TRH) after the operati...
Holyoak GR, Ma A.Historical evidence of acupuncture predates written history. It has been a component of Traditional Chinese veterinary medicine for many generations and is officially recognized in recorded history for treating equine disease in the Zhou Dynasty, circa 1050 BC. Drawing from a range of searchable databases, we present the use of veterinary acupuncture related to theriogenology. We touch on human-based medicine only as an introduction to current uses within veterinary medical acupuncture. This review is confined to the use of acupuncture encompassing dry needle, electroacupuncture, aquapuncture,...
