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Biomedical subjects

S L Alexander

Publications and source records attributed to S L Alexander.

At least 19 recordsLinked to original sources
PubMed2004

Spironolactone use in patients with heart failure.

BACKGROUND: The addition of spironolactone, an aldosterone antagonist, to standard therapy can reduce the risk of both morbidity and mortality in patients with severe heart failure. OBJECTIVE: To evaluate the use of spironolactone in class III and IV heart failure patients in four urban teaching hospitals. METHODS: We conducted a concurrent medical record review of 163 patients with documented heart failure admitted to a general medicine service over a 5-week period. Data retrieved included patient demographics, heart failure class, left ventricular ejection fraction, spironolactone contraindications, spironolactone use, dose and frequency, and other heart failure medication use, dose and frequency. All data reflected patients' baseline status. RESULTS: Our patient population was 80% white people, 61% male, with a mean age of 70 years (35-99). A total of 114 had class III or IV heart failure (70%). Angiotensin-converting enzyme inhibitors or appropriate alternative were prescribed in 117 (72%) patients, whereas beta-blockers were used in 121 (74%) patients. Fifty-seven patients met spironolactone ideal candidate criteria. Of these, eight (14%) were appropriately prescribed spironolactone. CONCLUSIONS: Three years after publication of the Randomized Aldactone Evaluation Study, spironolactone is underutilized in the treatment of heart failure. Results of this study indicated that the majority of patients in class III or IV heart failure were not prescribed spironolactone. Improvements in spironolactone prescribing are needed.

Adult↗
PubMed2004

Inter-relationships between the secretory dynamics of thyrotrophin-releasing hormone, thyrotrophin and prolactin in periovulatory mares: effect of hypothyroidism.

We used our nonsurgical technique for collecting pituitary venous blood to relate the dynamics of thyrotrophin-releasing hormone (TRH) secretion to the secretion patterns of both prolactin and thyrotrophin in periovulatory mares, either euthyroid (n = 5) or made hypothyroid by treatment with propyl-thiouracil (n = 5). Pituitary venous blood was collected continuously and divided into 1-min aliquots for 4 h. To test the effect of dopamine on the relationship between secretion patterns, sulpiride, a selective D2 receptor antagonist, was given i.m. after 2 h of sampling. Thorough testing of the model and blood collection procedure revealed no sites of TRH loss. Hypothyroidism increased the mean secretion rates of TRH (P = 0.04) and thyrotrophin (P < 0.0001) but not prolactin. Sulpiride increased prolactin secretion rates in hypothyroid (P < 0.0001) and control (P = 0.007) mares, but did not alter TRH or thyrotrophin secretion rates. In both groups of mares, all three hormones were secreted episodically but not rhythmically. In both groups, the secretion pattern of TRH was almost always significantly related to that of thyrotrophin, as assessed by cross correlation and cross approximate entropy (ApEn) analysis. However, the degree of linear correlation was weak, with only 14% (hypothyroid) or 8% (controls) of the variation in thyrotrophin secretion rates attributable to TRH. Prolactin and TRH secretion patterns before sulpiride were coupled on cross ApEn analysis in both groups, and the minute-to-minute secretion rates of the two hormones were correlated in four hypothyroid and three euthyroid mares. Overall, the small, but significant, degree of association between TRH and prolactin was similar to that between TRH and thyrotrophin. In hypothyroid mares, sulpiride increased (P = 0.02) the synchrony between TRH and prolactin patterns. We conclude that in horses: (i) little TRH degradation occurs during passage through the pituitary or in blood after 1 h at 37 degrees C; (ii) TRH is not the major factor controlling minute-to-minute fluctuations in either thyrotrophin or prolactin; and (iii) reducing two strongly inhibitory inputs (i.e. dopamine and thyroid hormones) may magnify the stimulatory effect of TRH on prolactin secretion.

Animals↗
PubMed2002

The effect of endotoxin administration on the secretory dynamics of oxytocin in follicular phase mares: relationship to stress axis hormones.

The primary aim of this study was to define the secretory dynamics of oxytocin and vasopressin in pituitary venous effluent from ambulatory horses during acute endotoxaemia, a stimulus that may release both hormones. Our secondary aim was to investigate the role of oxytocin in regulating adrenocorticotropic hormone (ACTH) secretion by comparing oxytocin, vasopressin, corticotropin-releasing hormone (CRH) and ACTH secretory profiles during endotoxaemia and by monitoring the ACTH response to oxytocin administration. Pituitary venous blood was collected nonsurgically continuously and divided into 1-min segments from eight follicular phase mares. Four mares were sampled for 30 min before and 3.5 h after receiving an i.v. infusion of bacterial endotoxin (TOX). Four control mares were sampled for 2.5 h without infusion of TOX. Another three follicular phase mares were given 5 U of oxytocin to replicate the peak response to TOX and pituitary blood collected every 1 min for 10 min before and 15 min after injection. Endotoxin raised the secretion rates of all hormones measured. All hormones were released episodically throughout the experiment, with TOX increasing the amplitude of peaks in each hormone. Peaks in oxytocin and vasopressin were coincident in each treated mare. Similarly, ACTH peaks were coincident with peaks of oxytocin and vasopressin in each treated mare, and with peaks of CRH in three mares. However, oxytocin administration did not affect ACTH secretion. We conclude that during endotoxaemia in horses: (i) oxytocin and vasopressin are secreted synchronously; (ii) oxytocin is unlikely to be acting as an ACTH secretagogue since inducing peak oxytocin concentrations observed during TOX does not raise ACTH; and therefore (iii) the close relationship between oxytocin and ACTH secretion is circumstantial and due to the fact that oxytocin secretion is concurrent with that of vasopressin, a proven ACTH secretagogue in horses.

Adrenocorticotropic Hormone↗
PubMed2002

Effectiveness of a two-dose regimen of prostaglandin administration in inducing luteolysis without adverse side effects in mares.

Our objectives were to determine whether repeated administration of prostaglandin F2alpha (PGF2alpha) to simulate the endogenous mode of secretion would be more effective than a single injection in inducing luteolysis and enable use of smaller doses less likely to cause adverse side effects. The main study comprised 43 dioestrous mares, who were given im. either a single 10 mg dose of natural PGF2alpha (n = 22) or 2 doses of 0.5 mg PGF2, 24 h apart (n = 21). The intensity of side effects was assessed in 8 dioestrous mares given 5, 1.5, 0.5 or 0 mg PGF2alpha in consecutive cycles. Two doses of 0.5 mg PGF2alpha 24 h apart caused lysis of the corpus luteum in all mares, whether this was determined from a fall in plasma progesterone concentrations or reproductive tract/behavioural changes; and when 10 mg PGF2, was given, the corpus luteum was lysed in 17 of 22 mares i.e. a lower proportion (P = 0.0485). A single dose of 0.5 mg PGF2a was no more effective than saline in inducing luteolysis.The intensity of side effects of PGF2alpha increased with dose. Although the 0.5 mg dose was no more likely than saline to cause sweating or muscle spasms, it raised plasma cortisol concentrations and prevented the decline in heart rate seen after saline. We conclude that a 2 dose regimen of administration increases the luteolytic efficacy of PGF2alpha and thereby provides a way to minimise adverse side effects.

Abortifacient Agents, Nonsteroidal↗
PubMed2001

Prospective study of 1 surgeon's experience with 115 cases using the Unfolder lens injection system.

PURPOSE: To describe the experience of 1 surgeon's first 115 cases using the Allergan Unfolder intraocular lens (IOL) injection system. SETTING: Free-standing day-surgery center, Chatswood, Australia. METHODS: After standard phacoemulsification, an SI-40NB IOL (Allergan) was implanted using the Unfolder. Data on complications and the success of implantation were collected prospectively. RESULTS: Ninety-four percent of patients achieved a 1 month visual acuity of 6/6 or better. Of the 13 cases with a potential complication related to the Unfolder, all achieved a visual acuity of 6/6 or better. No complication affected the eye adversely or reduced visual acuity significantly. CONCLUSION: Implantation of SI-40NB IOLs with the Unfolder led to no serious complications and gave satisfactory visual results.

Humans↗
PubMed2000

The effect of the alpha-2-adrenergic agonist, clonidine, on secretion patterns and rates of adrenocorticotropic hormone and its secretagogues in the horse.

Alpha-2-adrenoceptor activation may lower adrenocorticotropic hormone (ACTH) by reducing secretagogue input and/or increasing the release of an inhibitory factor (CIF). To investigate this, we gave clonidine, an alpha-2-agonist, to seven horses, and collected pituitary venous blood every minute for 20 min before treatment and 40 min after treatment. Six horses were given saline vehicle. Mean secretion rates of corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and ACTH were calculated before and during four 5-min then two 10-min periods after clonidine or saline. Reduction in ACTH secretion without corresponding changes in CRH and/or AVP would imply the presence of CIF. Secretion rates of ACTH (P = 0.008) and AVP (P = 0.0005) fell after clonidine and remained lower than baseline values for 20 min and 10 min, respectively. The CRH secretion rate decreased slightly but not significantly after clonidine. In controls, hormone secretion rates did not alter during the experiment. Multiple linear regression showed that CRH and AVP secretion accounted for 69% (treated) or 45% (controls) of the variation in ACTH secretion (P < 0.0001 for each). CRH alone contributed 80% (treated) or 76% (controls) of the fit to this model, which is consistent with the concept that CRH 'sets the gain' of the response of corticotrophs to fluctuations in AVP. Accordingly, minute-to-minute changes in pituitary concentrations of AVP and ACTH were synchronous when all data were considered (% concordant changes: controls, 68%, P < 0.0001; treated, 76%, P < 0.0001) and the percentage of concordant movement was unaffected by clonidine (before 72%; after 73%; P = 0.80). In treated horses but not controls, the ratio between the secretion rates of ACTH and AVP fell (P = 0.009), while the ACTH : CRH ratio tended to fall after clonidine, implying reduced responsiveness to stimulation. Moreover, one horse showed a drop in ACTH and a rise in CRH and AVP secretion after clonidine. We conclude that in horses alpha-2-adrenoceptor activation lowers ACTH secretion primarily by reducing the secretion of AVP and possibly CRH. While there was some evidence that a CIF may participate in the clonidine-induced suppression of ACTH, the subtlety of the discordance between ACTH and its secretagogues in most horses and the rarity of complete dissociation indicate that it does not play a major role.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2000

Reproductive hormone profiles in mares during the autumn transition as determined by collection of jugular blood at 6 h intervals throughout ovulatory and anovulatory cycles.

The aim was to define precisely the FSH secretion pattern in mares during the two ovulatory cycles before, and for 24 days after, the last ovulation of the season and to compare this with the profiles of other reproductive hormones and follicular growth to identify changes which may lead to the termination of follicular cycles. Jugular blood was collected every 6 h from ten light horse mares for 6 weeks in autumn. Samples were assayed for FSH, LH, prolactin, inhibin, oestrone conjugates and progesterone. Luteolysis occurred earlier and periovulatory oestrone, but not inhibin, concentrations were significantly lower in the last than in the second to last cycles. In ovulatory and anovulatory cycles, daily mean FSH concentrations were low at the expected time of ovulation and high between days 9 and 11 (day 0 = ovulation), which were usually after luteolysis. However, the periovulatory FSH nadir was prolonged in the last compared with the second to last cycles, and the difference between peak and trough values was not significant in anovulatory cycles. Between day 5 and day 8, the FSH interpulse interval was approximately 2 days, and did not vary in successive cycles. The LH profile also showed progressive changes as mares entered acyclicity; the surge terminated sooner in the last than in the second to last cycles, and failed to occur when expected in acyclicity. Sporadic prolactin pulses occurred at luteolysis in a similar proportion of ovulatory and anovulatory cycles. These results indicate that inadequate gonadotrophin stimulation in early dioestrus may be a critical event leading to suboptimal follicular and luteal development, and eventually acyclicity. Moreover, the time relationships amongst changes in pituitary and ovarian hormones and follicular growth become increasingly disrupted during the autumn transition, which may contribute to the cessation of cyclicity.

Analysis of Variance↗
PubMed1998

Artist's impression of endocapsular phacoemulsification surgery.

A 77-year-old artist having endocapsular phacoemulsification surgery and intraocular lens implantation illustrated her visual impressions of the procedure in 6 stages, from draping to lens implantation. Her illustrations and commentary indicate that she experienced clear visualization of instruments and colorful abstract imagery. These paintings were shown to 30 consecutive patients to assess their usefulness in preoperatively informing and preparing patients for surgery. With the widespread use of local and topical anesthesia, it is pertinent to the ophthalmic surgeon to understand what patients may seen when vision is retained during the procedure.

Aged↗
PubMed1998

Intraoperative complications of 1000 phacoemulsification procedures: a prospective study.

PURPOSE: To determine the frequency and nature of intraoperative complications of endocapsular phacoemulsification cataract surgery. SETTING: Dalcross Private Hospital and the Departments of Ophthalmology, Concord Hospital and Prince of Wales Hospital, Sydney, Australia. METHODS: This prospective study included the first 1000 cases of planned endocapsular phacoemulsification cataract surgery performed by an experienced surgeon. A standardized proforma was completed at the time of surgery. Data recorded included pre-existing ocular abnormalities, duration of surgery, nuclear sclerosis grade, and intraoperative complications. RESULTS: Major complications comprised posterior capsule tears with vitreous loss (1.4%), isolated posterior capsule tears (0.7%), and zonulysis (0.1%). Minor complications included anterior capsule tears (3.8%), iris prolapse (0.6%), and ciliary body incision (0.2%). There was a significant trend toward complications as the nuclear sclerosis grade increased. The incidence of major complications was 9.3% in the first 150 cases and 0.9% in the last 850. This represents a relative risk of 9.9 (95% confidence interval 4.2 to 23.0) of a major complication occurring in the first 150 compared with the later 850 cases. CONCLUSION: The frequency of major and minor complications fell sharply after the first 150 operations and was maintained. This study may provide a guide for beginning phacoemulsification surgeons and a basis for experienced surgeons to compare their performance outcomes.

Adult↗
PubMed1998

Daily intake and urinary excretion of genistein and daidzein by infants fed soy- or dairy-based infant formulas.

Our aims were to measure isoflavone intake from soy- and dairy-based infant formulas and breast milk and to assess the ability of infants to digest and absorb soy isoflavones by measuring daily urinary excretion rates. We recruited 29 infants: 4 received soy-based formula and 25 received dairy-based formula. We collected pooled urine samples from 3-5 disposable diapers worn during a 24-h period and developed and validated methods for extracting isoflavones from the diapers. Infants were studied every 1 or 2 wk, starting at 2-6 wk of age and continuing until 16 wk. Only soy-based formulas contained isoflavones in concentrations detectable by HPLC (limits: 0.05 mg/L for liquids and 0.1 mg/kg for solids). Soy-based formulas provided a mean (+/-SEM) daily dose of isoflavones (genistein plus daidzein) of 3.2 +/- 0.2 mg/kg body wt, which remained fairly constant (CV: 12%) regardless of age < or = 16 wk. Isoflavones were measurable in all samples from soy-fed infants, but not in urine from dairy-fed infants. Daily isoflavone excretion rates varied little among infants [range of mean individual values (mg x kg(-1) d(-1)): daidzein, 0.37 +/- 0.03 to 0.58 +/- 0.06; genistein, 0.15 +/- 0.03 to 0.32 +/- 0.04] and did not change with age < or = 16 wk. The mean percentage of the daily intake recovered in the urine of soy-fed infants was 38 +/- 4% for daidzein and 13 +/- 3% for genistein, and remained constant with age. These values are similar to those for adults and indicate that young infants are able to digest, absorb, and excrete genistein and daidzein from soy-based formulas as efficiently as do adults consuming soy products.

Adult↗
PubMed1998

Gonadotrophin profiles and dioestrous pulsatile release patterns in mares as determined by collection of jugular blood at 4 h intervals throughout an oestrous cycle.

In mares, dioestrous FSH profiles based on once-a-day sampling are variable; however, the pulsatility of plasma FSH, which has been suggested by limited windows of intensive sampling, may contribute to this variability. Jugular blood from six mares was sampled at 4 h intervals throughout an ovulatory cycle to determine cyclic FSH and LH patterns more accurately and to measure gonadotrophin pulse frequency during dioestrus. Synchronous pulses of FSH and LH occurred regularly in all mares between day 4 and day 12 (ovulation = day 0) with a mean (+/- SEM) frequency of 1.9 +/- 0.1 (FSH) or 1.6 +/- 0.1 (LH) pulses day-1. LH pulse amplitude declined (P < 0.0001) between day 4 and day 10, but FSH pulse amplitude remained large and stable, dipping slightly but not significantly on day 6. Daily mean FSH concentrations exceeded (P < 0.0001) early oestrous values between day 4 and day 5, and between day 7 and day 10. However, significantly different patterns were obtained when once-a-day sampling was simulated by selecting samples collected at 08:00 h or noon. LH was higher during the periovulatory surge than during dioestrus (P < 0.0001) and profiles were similar whether daily means or selected samples were used. It is concluded that: (1) the marked pulsatility of plasma FSH during dioestrus makes once-a-day sampling misleading for determining FSH profiles; (2) the dioestrous pattern of large, slow FSH pulses was consistent among mares, unlike that of the daily mean FSH profiles; and (3) no discrete FSH 'surges' were observed during dioestrus, although FSH pulse amplitude tended to undergo alternate increases and decreases. A period of higher amplitude FSH pulses preceded ovulation by 10.2 +/- 0.7 days, which corresponds to the approximate time the ovulatory follicle emerges. Therefore, it is possible that the signal for follicular recruitment in mares is intermittent excursions of plasma FSH above a threshold value.

Animals↗
PubMed1998

The effect of social stress on adrenal axis activity in horses: the importance of monitoring corticosteroid-binding globulin capacity.

Plasma cortisol is largely bound to corticosteroid-binding globulin (CBG), which regulates its bioavailability by restricting exit from capillaries. Levels of CBG may be altered by several factors including stress and this can influence the amount of cortisol reaching cells. This study investigated the effect of social instability on plasma concentrations of CBG, total and free (not protein bound) cortisol in horses. Horses new to our research herd ('newcomers') were confined in a small yard with four dominant resident horses for 3-4 h daily for 3-4 (n = 5) or 9-14 (n = 3) days. Jugular blood was collected in the mornings from newcomers before the period of stress began ('pre-stress'), and then before each day's stress. Residents were bled before stress on the first and thirteenth day. Residents always behaved aggressively towards newcomers. By the end of the stress period, all newcomers were subordinate to residents. In newcomers (n = 8) after 3-4 days of social stress, CBG binding capacity had fallen (P = 0.0025), while free cortisol concentrations had risen (P = 0.0016) from pre-stress values. In contrast, total cortisol did not change. In residents, CBG had decreased slightly but significantly (P = 0.0162) after 12 days of stress. Residents and newcomers did not differ in pre-stress CBG binding capacity, total or free cortisol concentrations. However, by the second week of stress, CBG binding capacity was lower (P = 0.015) and free cortisol higher (P = 0.030) in newcomers (n = 3) than in residents. Total cortisol did not differ between the groups. In conclusion social stress clearly affected the adrenal axis of subordinate newcomer horses, lowering the binding capacity of CBG and raising free cortisol concentrations. However, no effect of stress could be detected when only total cortisol was measured. Therefore, to assess adrenal axis status accurately in horses, it is essential to monitor the binding capacity of CBG and free cortisol concentrations in addition to total cortisol levels.

Adrenal Cortex↗
PubMed1998

Phytoestrogens in soy-based infant foods: concentrations, daily intake, and possible biological effects.

Exposure to estrogenic compounds may pose a developmental hazard to infants. Soy products, which contain the phytoestrogens, genistein and daidzein, are becoming increasingly popular as infant foods. To begin to evaluate the potential of the phytoestrogens in these products to affect infants, we measured total genistein and daidzein contents of commercially available soy-based infant formulas, infant cereals, dinners, and rusks. We also assayed phytoestrogens in dairy-based formulas and in breast milk from omnivorous or vegetarian mothers. In most cases, the glucoside forms of the phytoestrogens were hydrolyzed before separation by HPLC. Mean (+/-SEM) total genistein and daidzein contents in four soy infant formulas were 87+/-3 and 49+/-2 microg/g, respectively. The phytoestrogen content of cereals varied with brand, with genistein ranging from 3-287 microg/g and daidzein from 2-276 microg/g. By contrast, no phytoestrogens were detected in dairy-based infant formulas or in human breast milk, irrespective of the mother's diet (detection limit = 0.05 microg/ml). When fed according to the manufacturer's instruction, soy formulas provide the infant with a daily dose rate of total isoflavones (i.e., genistein + daidzein) of approximately 3 mg/kg body weight, which is maintained at a fairly constant level between 0-4 months of age. Supplementing the diet of 4-month-old infants with a single daily serving of cereal can increase their isoflavone intake by over 25%, depending on the brand chosen. This rate of isoflavone intake is much greater than that shown in adult humans to alter reproductive hormones. Since the available evidence suggests that infants can digest and absorb dietary phytoestrogens in active forms and since neonates are generally more susceptible than adults to perturbations of the sex steroid milieu, we suggest that it would be highly desirable to study the effects of soy isoflavones on steroid-dependent developmental processes in human babies.

Child Development↗
PubMed1997

Patterns of secretion of GnRH, LH and FSH during the postovulatory period in mares: mechanisms prolonging the LH surge.

To study the mechanisms responsible for the unusually slow decline of the ovulatory LH surge in mares, secretion patterns of GnRH, LH and FSH were monitored in pituitary venous blood collected every 2 or 5 min for 10.5-18.0 h from five mares on the third (n = 4) or fifth day after ovulation (first sampling period). To determine the effectiveness of progesterone negative feedback, mares were then given a luteolytic dose of a prostaglandin analogue (PGF2 alpha) and pituitary venous sampling (every 2 or 5 min for 16 h) recommenced 20-22 h later (second sampling period). During the declining arm of the LH surge, large peaks (detected by the Cluster algorithm) of concurrent LH and FSH secretion occurred infrequently, with four peaks being detected in a combined sampling period of 75 h. Outside the peaks, LH or FSH secretion continued (as assessed by a pituitary to jugular-venous concentration ratio > or = 1.25) during 46% +/- 13 or 40% +/- 10, respectively, of the sampling period. GnRH immunoactivity was detected during each spontaneous gonadotrophin peak, but at other times was generally at assay sensitivity. After PGF2 alpha, plasma progesterone fell (ng ml-1, mean +/- SEM; first sampling period: 8.6 +/- 0.8; second; 2.0 +/- 0.3; P = 0.001) and the frequency of LH (P < 0.05) and FSH (P < 0.02) peaks rose, with 28 peaks detected for each hormone in a total of 80 h sampling. Peaks in LH were smaller during the second period, with decreases observed in maximum (P = 0.027) and mean (P = 0.025) secretion rates. Maximum GnRH secretion rate during peaks also declined (P = 0.010); however, the decrement (-30 +/- 6%) was less than that in maximum LH secretion rate (-82 +/- 5%; P = 0.040), suggesting that other factors contribute to the reduced LH peak amplitude. In summary, gonadotrophin peak frequency during the downswing of the surge in mares is slow, as in the midluteal phase, and the slow rate of decline in peripheral gonadotrophin concentrations is due, at least in part, to continued secretion between pulses. Moreover, progesterone negative feedback is highly effective in early dioestrus, in that lessening it without complete removal markedly accelerates gonadotrophin pulse frequency.

Animals↗
PubMed1997

Effect of insulin-induced hypoglycaemia on secretion patterns and rates of corticotrophin-releasing hormone, arginine vasopressin and adrenocorticotrophin in horses.

To study the effect of hypoglycaemia on secretion rates of corticotrophin-releasing hormone (CRH), arginine vasopressin (AVP) and ACTH in a non-ruminant species, a non-surgical method was used to collect pituitary venous (PitVen) blood every 0.5 or 1 min from seven horses before and after insulin administration (0.4 U/kg i.v.). To assess the effect of PitVen cannulation on results, peripheral hormones were also measured before and after insulin in five horses without PitVen cannulae. Insulin administration lowered plasma glucose in all horses (P < 0.0001; paired t-test). Cortisol concentrations, which were similar in horses with and without PitVen cannulae before insulin, rose significantly after insulin administration in both groups. Most horses showed discomfort as glucose fell. When data from horses with and without PitVen cannulae were pooled, the peak fractional change in cortisol (Spearman's rank correlation coefficient (rs) = -0.94, P < 0.001) and the severity of hypoglycaemic symptoms (rs = -0.61, P < 0.02) were inversely ranked with the glucose nadir. In horses with PitVen cannulae, insulin administration increased secretion rates of ACTH (P < 0.0001), AVP (P < 0.0001) and CRH (P < 0.02). Increments in ACTH (rs = -0.96, P < 0.005) and CRH (rs = -0.81, P < 0.05), but not in AVP, measured during the second half-hour after insulin (i.e. the peak response), were inversely ranked with the glucose nadir. Moreover, ACTH increments were positively ranked with those in CRH (rs = 0.81, P < 0.05), but not in AVP. Nevertheless, in individual horses, minute-to-minute AVP and ACTH concentrations in PitVen blood were always correlated, whereas minute-to-minute CRH and ACTH concentrations were correlated only when glucose dropped below 3.4 mmol/l. In less hypoglycaemic horses, ACTH secretion rose despite little or no change in CRH. We suggest that in horses AVP is the primary acute signal for ACTH release both before and during hypoglycaemia; however, the increasing magnitude of ACTH increments induced by greater degrees of hypoglycaemia is determined largely by selective CRH release, which then augments corticotroph responses to AVP.

Adrenocorticotropic Hormone↗
PubMed1996

Dynamics of the regulation of the hypothalamo-pituitary-adrenal (HPA) axis determined using a nonsurgical method for collecting pituitary venous blood from horses.

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 secretagogues can be precisely defined. When PitVen blood was sampled every 20 or 30s during the circadian maximum, arginine vasopressin (AVP) and ACTH secretion patterns were complex and irregular, with mean interpeak intervals of approximately 5 min. Despite their erratic patterns, AVP and ACTH secretions were closely coupled on cross-correlation analysis. By contrast, PitVen corticotropin-releasing hormone (CRH) concentrations were low, relatively stable, and not consistently related to ACTH secretion. However, when cortisol negative feedback was reduced acutely by metyrapone infusion, CRH and AVP secretion were stimulated. Mathematical modeling suggested that CRH had become the more effective secretagogue and that much of the ACTH response was mediated by increased pituitary responsiveness to CRH. Elevated blood osmolality triggered synchronous AVP and ACTH secretion, without altering PitVen CRH. In this case, the source of PitVen AVP was presumably the magnocellular/neurohypophysial pathway, which is thought to respond primarily to changes in blood osmolality and pressure. Our results suggest that this pathway also participates in ACTH regulation. We have studied the effect of several perturbations and found, as have others, that the secretagogues released vary with the stimulus given. For example, vigorous exercise promptly raised PitVen AVP and ACTH, but not PitVen CRH. Hypoglycemia provoked both CRH and AVP secretions, with the CRH increment being inversely proportional to the glucose nadir. Administration of the opioid antagonist, naloxone, increased PitVen ACTH; however, changes in AVP and CRH were variable and overall could not account for the ACTH response. This suggests that endogenous opioids inhibit a third ACTH secretagogue, stimulate an inhibitory factor, or also act at the pituitary. Chronic social stress, induced by confining newcomers with aggressive, resident mares, caused most introduced horses to become submissive. In such horses, plasma cortisol declined to levels similar to those during metyrapone infusion. Despite hypocortisolemia, PitVen ACTH was low, whereas PitVen CRH tended to be elevated. Moreover, chronically stressed horses did not respond to exogenous CRH. We conclude that at rest and during some perturbations AVP is the immediate stimulus for ACTH release. Even ACTH micropulses, previously thought to occur spontaneously, appear to be regulated by AVP in horses. On the other hand, CRH secretion and pituitary responsiveness to CRH rise when cortisol falls, suggesting that a major role for CRH is to fix the cortisol setpoint. However, during chronic stress, these relationships become disturbed, with results to date pointing toward the existence of an ACTH-release inhibiting factor.

Adrenal Glands↗