Mean Cortisol Concentrations Research Articles

Effects of Naloxone on the Preparturient Increase in Adrenocorticotrophin and Cortisol in Foetal Sheep

Abstract Parturition in sheep is preceded by a rapid increase in foetal pituitary-adrenal activity. Administration of exogenous opioids increases foetal plasma adrenocorticotrophin (ACTH) and cortisol concentrations after Day 125 of pregnancy (term = 145 days). In order to test the hypothesis that endogenous opioids regulate the increase in pituitary-adrenal activity prior to parturition in foetal sheep, we measured changes in plasma ACTH and cortisol in response to administration of either naloxone (1.2 mg intravenous bolus followed by a 2.5 mg/h continuous infusion for 2 h; foetal body weight approximately 2.5 kg) or saline to chronically catheterized foetal sheep at 2-day intervals between Day 140 and the onset of parturition. In addition, we utilized a computerized algorithm (Munro) to examine the precise characteristics of ACTH and cortisol secretion in control and naloxone-treated foetuses. The pattern of ACTH and cortisol secretion in saline-infused control foetuses was highly pulsatile but varied considerably between individual foetuses. ACTH pulses occurred on average every 40 min but were not always coincident with pulses of cortisol. There were no significant changes in average ACTH concentrations, pulse frequency or amplitude between foetuses sampled at 3 to 4 and 1 to 2 days before parturition. In contrast, average cortisol concentrations and pulse amplitude were significantly (P < 0.05) increased, whereas pulse frequency was reduced, in foetuses at 1 to 2 days before parturition. Naloxone caused a significant (P < 0.05) inhibition of ACTH concentrations when compared with pretreatment values and with saline-treated controls, an effect which persisted for at least 2 h after the end of naloxone infusion. However, there were no significant differences during naloxone treatment in the frequency or amplitude of ACTH or cortisol pulses nor in the mean cortisol concentration. We conclude that ACTH and cortisol are secreted in a pulsatile fashion in the late gestation foetal sheep and that these pulses are not always coincident with each other. Blockade of endogenous opioid activity during the preparturient increase in pituitary-adrenal activity in foetal sheep, results in a reduction in plasma concentrations of ACTH. These results therefore provide evidence for the tonic regulation of foetal pituitary-adrenal activity by endogenous opioids during the final days prior to birth in the sheep.

Slowing of Pulsatile Luteinizing Hormone Secretion in Men after Forty-Eight Hours of Fasting

To determine whether short periods of fasting can suppress the activity of the reproductive axis in normal healthy men, eight men were studied on a fed day and again after 48 h of fasting. Subjects were between 20-32 yr of age and ranged from 84-119% of normal body weight. Blood samples were collected on day 1 (a fed day) and day 3 (after 48 h of fasting) at 15-min intervals from 0800-1600 h through indwelling venous catheters. Fasting for 48 h resulted in a significant decrease in mean LH, FSH, and testosterone concentrations. The mean LH concentration decreased from 2.94 +/- 0.59 IU/L on the fed day to 1.07 +/- 0.14 IU/L after 48 h of fasting, and there was an accompanying decrease in LH pulse frequency (from 5.13 +/- 0.29 to 2.63 +/- 0.62 pulses/8 h) and mean baseline LH concentration (from 1.83 +/- 0.52 to 0.51 +/- 0.07 IU/L), but no significant decrease in LH pulse amplitude. In a second study, blood samples were collected from five subjects who were allowed to eat normally between days 1 and 3; these individuals showed no difference in LH secretion. To begin to examine the possibility that an activation of the hypothalamic-pituitary-adrenal axis leads to the suppression of reproductive hormone levels that occurred after 48 h of fasting, cortisol levels were measured in all plasma samples. There was no significant difference in mean cortisol concentrations on fed vs. fasted days or when cortisol concentrations were examined as hourly means across the 2 days. These results indicate that activity of the reproductive axis can be suppressed in normal healthy men by 48 h of fasting. It appears unlikely that activation of the adrenal axis is the cause of this suppression of reproductive axis activity.

Effects of dietary energy level on luteinizing hormone and adrenal function in the post partum beef cow

The effects of dietary energy and suckling on adrenal function and luteinizing hormone (LH) concentrations were investigated in primiparous postpartum cows. Ten heifers were assigned at calving to either high (22.8 Mcal/day) or low (15.2 Mcal/day) energy diets. Blood samples were collected every 15 minutes for 8 hours on 28, 42, and 56 days post partum. Calves were allowed to suckle ad libitum during sampling periods. Serum samples were analyzed by radioimmunoassay for LH and cortisol. Concentrations of catecholamines were quantified by reverse-phase HPLC. Body weights were decreased (P<0.01) by low energy intake. In addition, low energy diet cows had lower mean LH concentrations (0.97 ± 0.09 vs 1.57 ± 0.07 ng/ml), P<0.05) than high energy diet cows. Luteinizing hormone concentrations in high energy diet cows increased with days post partum, resulting in a treatment-by-time interaction (P<0.005). Treatment did not affect mean cortisol concentrations. However, within 15 minutes of suckling cortisol release was significantly above baseline in 77% of the observed suckling events. Dihydroxyphenylalanine (DOPA) increased in high energy diet cows compared with that of low energy diet cows (2,833 ± 243 vs 1,294 ± 243 pg/ml, P<0.01). Norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC) were not influenced by treatment. Plasma NE decreased during the postpartum interval (P<0.005). These data suggest that reduced energy intake may prevent the increase in LH associated with increasing days post partum and alter adrenal function. In addition, spontaneous suckling events elicit a release of cortisol.

Mitotane (o, p‘‐DDD) Treatment of 200 Dogs with Pituitary‐Dependent Hyperadrenocorticism

Two hundred dogs with pituitary dependent hyperadrenocorticism (PDH) were treated with mitotane at an initial daily dosage of 21 to 69 mg/kg (mean = 45.2 mg/kg) for 5 to 14 days. During the induction period, 194 of the dogs also were given daily maintenance dosages of a glucocorticoid. Fifty of the dogs exhibited one or more adverse effects during initial induction, including weakness, vomiting, anorexia, diarrhea, and ataxia. After completion of the induction period, repeat ACTH stimulation testing revealed significant decreases in mean serum cortisol concentrations when compared with initial values. Twenty-five dogs, however, still responded to exogenous ACTH with serum cortisol concentrations above normal resting range, necessitating daily treatment for an additional 5 to 55 days. In contrast, 70 of the 200 dogs had low post-ACTH serum cortisol concentrations after the induction period. These subnormal serum cortisol concentrations generally increased spontaneously to within normal resting range 2 to 6 weeks after cessation of mitotane. In 184 dogs, mitotane was continued at an initial mean maintenance dosage of 49 mg/kg administered weekly in two to three divided doses. Of these dogs, 107 had one or more relapses of hyperadrenocorticism during treatment. In the 75 dogs that had one relapse, the median maintenance dosage was increased by approximately 35%, whereas the median maintenance dosage in the 32 dogs having two or more relapses was eventually increased by 225% over the initial dosage. After a mean maintenance treatment time of 2.0 years, the final maintenance dosage required in the 184 dogs ranged from 26.8 to 330 mg/kg/week.(ABSTRACT TRUNCATED AT 250 WORDS)

Free-running rhythms of adrenocorticotropic hormone (ACTH), cortisol and melatonin in pigs

In the domestic pig, a circadian rhythm of plasma cortisol occurs, with greatest concentrations in the morning and lowest concentrations in the afternoon. However, photic entrainment of the rhythms of ACTH and melatonin in pigs have not been defined clearly. This experiment was designed to evaluate free-running rhythms of ACTH, cortisol and melatonin in pigs housed in constant light (LL) and constant darkness (DD). Twelve crossbred barrows, maintained under ambient photoperiod, were catheterized and tethered individually in two environmentally controlled rooms, one with LL and the other with DD. For animals in LL, fluorescent lights provided 202 ± 15 (mean ± standard deviation) lux of light at 65 cm above the floors. Incandescent nightlights equipped with 7 watt red bulbs provided 7 ± 2 lux and were illuminated continuously in both rooms. Pigs were given at least 14 d exposure to LL and DD, then samples of plasma and serum were obtained at hourly intervals for 48 hr. Plasma was assayed for ACTH, and serum for cortisol and melatonin. Periodograms were constructed to analyze the data. For this type of analysis, a statistic, Q p, is calculated, and circadian periodicity is suggested if maximum Q p (Q p max) occurs at or near 24 hr. The period of the free-running rhythms (τ) at Q p max for ACTH, cortisol and melatonin for pigs in LL (23.80 ± .01, 23.78 ± .01, and 23.21 ± .02 hr, respectively) did not differ significantly from those for pigs in DD (23.39 ± .01, 23.20 ± .01, and 22.55 ± .02 hr, respectively). For both treatments combined, Q p at τ=24 hr was greater (P < .05) than Q p at τ=20, 21, 25, 26, 27 and 28 hr for all three hormones. Unexpectedly, mean concentration of ACTH was greater (P < .005) and melatonin was less (P < .005) for pigs in DD (119.1 ± 4.2 pg/ml ACTH and 7.4 ± 1.5 pg/ml melatonin) compared to LL (67.9 ± 4.0 pg/ml ACTH and 26.1 ± 1.5 pg/ml melatonin). However, mean concentration of cortisol was similar for pigs in LL (22.7 ± .8 ng/ml) and DD (21.6 ± .8 ng/ml). In conclusion, rhythms of ACTH, cortisol and melatonin exist in constant photic conditions in pigs, with periodicity close to 24 hr. In addition, secretion and(or) disposition of ACTH and melatonin may be altered in pigs deprived of a light:dark cycle.

An Inhibitory Effect of Interleukin-la on Basal Gonadotropin Release in the Ovariectomized Rhesus Monkey: Reversal by a Corticotropin-Releasing Factor Antagonist*

Interleukin-1 (IL-1), an important component of the immune system, has recently been shown to influence the release of several hormones in the rodent. In this paper, the effectiveness of IL-1a in modulating basal gonadotropin secretion as well as cortisol release in the primate has been investigated. Eight adult ovariectomized rhesus monkeys were given a 30-min intracerebroventricular infusion of physiological saline (n = 5), various doses of IL-1a (17 micrograms n = 5; 8.5 micrograms; n = 3; 4.2 micrograms n = 5; and 2.1 micrograms n = 4) or IL-1a plus a CRF antagonist (n = 5). LH and FSH concentrations were measured at 15-min intervals during the 3-h preinfusion baseline control and the 5-h postinfusion period, while cortisol concentrations were determined at 45-min intervals. While LH concentrations remained unchanged in the monkeys receiving saline only, they decreased significantly after the 30-min IL-1a infusion. By hour 5 after IL-1a administration, mean (+/- SE) hourly areas under the LH curves (expressed as a percentage of preinfusion baseline) were 27.7% +/- 7.3 (17 micrograms IL-1a), 31.9% +/- 8.4 (8.5 micrograms), 33.3% +/- 5.5 (4.2 micrograms), and 39% +/- 4.0 (2.1 micrograms) (P less than 0.05 vs. morning control). FSH concentrations were also significantly decreased after IL-1a, 17 micrograms: by hour 5, they were 67.4% +/- 5.0 of baseline control. While cortisol concentrations decreased thoughout the experiment in the animals receiving saline, they increased with all IL-1a doses: overall mean (+/- SE) postinfusion concentrations were 21.8 +/- 1.1 (saline), 49.5 +/- 2.2 (IL-1a, 17 micrograms), 35.1 +/- 1.9 (8.5 micrograms), 45.7 +/- 1.5 (4.2 micrograms), and 39.5 +/- 1.5 (2.1 micrograms) micrograms/dl (P less than 0.05 IL-1a vs. saline). Concomitant infusion of the CRF antagonist, [D-Phe12, NLE 21,38caMe LEU37] CRF (12-41), (120-360 micrograms), prevented the IL-1a induced LH inhibition. By hour 5, areas under LH curves were 33.5% +/- 1.7 for IL-1a alone and 99.2% +/- 4.2 (NS vs. saline) for IL-1a + CRF antagonist. The CRF antagonist also blocked the ability of IL-1a to increase cortisol secretion: mean cortisol concentrations were 28.6 +/- 1.4 micrograms/dl (NS vs. saline). The results clearly indicate that the cytokine IL-1a inhibits pulsatile LH and FSH secretion in the ovariectomized rhesus monkey and demonstrate that this inhibition is causally related to the activation of CRF by this cytokine.(ABSTRACT TRUNCATED AT 400 WORDS)

Influence of reproductive state on pituitary-adrenal activity in the ewe

Plasma corticosteroid concentrations are altered in pregnancy, during the reproductive cycle and by ovariectomy in many species. This study was designed to examine basal ACTH and cortisol in ewes of four different reproductive statuses: ovariectomized, nonpregnant cycling, nonpregnant noncycling, and pregnant. Blood samples were drawn every 4 hr for 48 hr from ewes during quiet, undisturbed conditions and analyzed for plasma ACTH, cortisol and progesterone concentrations. There were no significant changes in ACTH, cortisol or progesterone over time. Mean progesterone concentrations were significantly greater in the pregnant ewes than in all other ewes, and were greater in cycling ewes than noncycling or ovariectomized ewes. Mean ACTH was significantly greater in pregnant ewes than noncycling ewes, and mean cortisol was significantly greater in cycling ewes than in nonpregnant cycling or noncycling ewes. Ovariectomized ewes also had significantly greater mean cortisol concentrations than cycling ewes. The results demonstrate that there is an increase in basal ACTH and cortisol in ovine pregnancy.

EFFICACY AND STRESS OF CHEMICAL VERSUS SURGICAL CASTRATION OF CATTLE

Blood was collected at 0, 3, 6, 12, 24, 36 and 48 h postcastration and then daily for a further 6 d to determine the degree of stress following surgical or chemical castration (Chem-cast; α-hydroxypropionic acid) of Holstein calves. Stress indicators (plasma cortisol, packed cell volume, glucose, proteins, free fatty acids, creatinine, urea nitrogen and rectal temperature) were measured for all castrates and compared with entire bull calves. There were no effects on stress indicators except plasma cortisol. Plasma cortisol concentrations were significantly elevated at 3 and 6 h postcastration in castrated compared with in-tact cattle (P &lt; 0.05). At these times, plasma cortisol concentrations in surgical castrates were greater than chemical castrates (P &lt; 0.05). Greatest concentrations of cortisol were measured at 6 h following surgical castration (23.2 ± 0.64 μg L−1) and at 3 h following chemical castration (16.8 ± 0.49 μg L−1). Mean cortisol concentration in calves not castrated was 7.1 ± 0.26 μg L−1. From 12 h to 7 d postcastration, differences between groups for plasma cortisol were not significant. It was concluded that acute stress occurred for 6–12 h following castration and that surgical castration caused greater stress than chemical castration. There was an immediate decline in plasma testosterone levels in surgically castrated calves and these remained at undetectable levels throughout a 63-d postcastration period. Testosterone levels of chemically castrated calves declined immediately following the injection of Chem-cast but there was a gradual increase to, and long term maintenance of, low levels of testosterone which were greater than those of surgical castrates (P &lt; 0.01) but less than those of entire males (P &lt; 0.01). Palpation indicated severe testicular degeneration in chemically castrated males. The average daily gains (ADG) over the entire experimental period of 133 d did not differ between the entire males (1.1 ± 0.11 kg d−1) and surgical castrates (0.9 ± 0.05 kg d−1) or between the entire males and chemical castrates (1.2 ± 0.04 kg d−1) but ADG for chemical castrates was greater than that for surgical castrates (P &lt; 0.05). Key words: Castration, Chem-cast®, stress, cattle, cortisol, testosterone

Suppression of endogenous cortisol for evaluating pharmacodynamics of prednisolone in early allograft rejection in renal transplantation

Concentrations of endogenous cortisol were examined in 34 kidney-transplant recipients by improved "high-performance" liquid chromatography. Ten recipients were treated with prednisolone and azathioprine, the others with prednisolone and cyclosporine. Peripheral serum samples were collected just before transplantation, daily for two weeks after the transplant, weekly until discharge for about two months, and then monthly or occasionally. Mean (+/- SD) cortisol concentrations, initially 145 +/- 87 micrograms/L, decreased immediately to 5.93 +/- 5.11 micrograms/L after transplant, remained at almost these same values for two months, and then swiftly increased to 51 +/- 59 micrograms/L by 1000 days. Cortisol concentrations within the period characterized by a cumulative dose of prednisolone at 300-700 mg were correlated significantly with the presence or absence of acute allograft rejection; patients with cortisol greater than 4 micrograms/L had a higher risk of rejection. The majority of stable patients showed cortisol concentrations between 1 and 4 micrograms/L throughout the cumulative prednisolone period characterized above. Concentrations less than 1 microgram/L after high-dose administration of methylprednisolone were accompanied by severe lung infection. We conclude that suppressed concentrations of endogenous cortisol, as assessed by highly specific HPLC, might provide a basis for predicting the therapeutic efficacy and adverse effects of prednisolone.

Effects of age, sex, and body size on serum concentrations of thyroid and adrenocortical hormones in dogs

SUMMARY Thyroxine (T4), 3,5,3′-triiodothyronine (T3), and cortisol frequently are quantified in canine serum or plasma samples to aid in the diagnosis of hypothyroidism, hypoadrenocorticism, and hyperadrenocorticism. Many laboratories have established reliable references values for concentrations of these hormones in blood of clinically normal animals. However, nonpathologic factors that affect thyroidal and adrenocortical secretion may lead to misinterpretation of test results when values for individual animals are compared with reference values. The objective of the study reported here was to identify effects of age, sex, and body size (ie, breed) on serum concentrations of T3, T4, and cortisol in dogs. Blood samples were collected from 1,074 healthy dogs, and serum concentrations of the iodothyronines and cortisol were evaluated for effects of breed/size, sex, and age. Mean (± sem) serum concentration of T4 was greater in small (2.45 ± 0.06 μg/dl)- than in medium (1.94 ± 0.04 μg/dl)- or large (2.03 ± 0.03 μg/dl)-breed dogs, the same in females (2.11 ± 0.04 μg/dl) and males (2.08 ± 0.04 μ/dl), and greater in nursing pups (3.04 ± 0.05 μg/dl) than in weanling pups (1.94 ± 0.05 μg/dl), rapidly growing dogs (1.95 ± 0.04 μg/dl), and young adult (1.90 ± 0.06 μg/dl), middle-aged adult (1.72 ± 0.05 μg/dl), or old adult (1.50 ± 0.05 μg/dl) dogs. Dogs &gt; 6 years old had lower mean serum T4 concentration than did dogs of all other ages, except middle-aged adults. Mean serum T3 concentration in medium-sized dogs (1.00 ± 0.01 ng/ml) was greater than that in small (0.90 ± 0.01 ng/ml)- and large (0.88 ± 0.01 ng/ml)-breed dogs. Serum T3 concentration was lowest in nursing (0.85 ± 0.01 ng/ml) and weanling (0.77 ± 0.02 ng/ml) pups, increased in rapidly growing dogs (0.99 ± 0.01 ng/ml) and young adult dogs (1.10 ± 0.04 ng/ml), and decreased slightly in middleaged (0.98 ± 0.02 ng/ml) and old (1.01 ± 0.03 ng/ml) adult dogs. Serum T3 concentration was unaffected by sex. Mean serum cortisol concentration was greater in small (1.06 ± 0.07 μg/dl)- than in large (0.79 ± 0.03 μg/ dl)-breed dogs. Serum from nursing pups (0.57 ± 0.04 μg/ dl) contained less cortisol than did serum from older dogs (mean values ≥ 0.92 μg/dl). Serum cortisol concentration was not different between males and females. These effects of breed/size and age on serum T3, T4, and cortisol concentrations should be considered when evaluating thyroid and adrenocortical functions in dogs.

Differences between concentrations of salivary cortisol and cortisone and of free cortisol and cortisone in plasma during pregnancy and postpartum

We measured cortisol and cortisone in plasma--both total and free--and in saliva during the course of pregnancy and postpartum. Antepartum and postpartum concentrations and morning and afternoon concentrations of both steroids were compared. The mean concentrations of cortisol and cortisone increased towards term and were significantly greater at the end of pregnancy than postpartum, except for free cortisol in plasma in the afternoon. The daily rhythm of both steroids was maintained throughout pregnancy and postpartum. The correlations between salivary and plasma free concentrations of cortisol and cortisone as well as of the sum of cortisol + cortisone were highly significant. The mean concentrations of cortisone in saliva accurately reflected both total and free concentrations in plasma. For cortisol, however, the change of the concentrations in saliva, was somewhat different from that in plasma. Moreover, the mass ratio of plasma free cortisol to salivary cortisol was about 2, whereas for cortisone the ratio was only about 0.5, probably owing to the conversion of cortisol to cortisone by 11 beta-hydroxysteroid dehydrogenase in the salivary gland. Furthermore, the passage of cortisol and cortisone from plasma to saliva should not be regarded as simple diffusion, because in the first half of pregnancy the sum of the concentrations of cortisol + cortisone in saliva significantly exceeded the sum of their free concentrations in plasma.

Adrenal cortical response in clinically normal dogs before and after adaptation to a housing environment

58 dogs (29 males and 29 females) selected as healthy on clinical and biochemical evaluations were subjected to an ACTH adrenal function test 2 days after their admission to a veterinary hospital (t + 0). Basal female serum cortisol concentrations were significantly higher than concentrations in males (77 nmol/l versus 43 nmol/l; P less than 0.01). Concentrations post stimulation were not statistically different (P greater than 0.05) between males and females: 306 (+/- 69) nmol/l versus 291 (+/- 73) nmol/l, respectively. Twelve dogs (6 males and 6 females), randomly selected from the 58, were subjected to the same test 5 weeks later (t + 5) and 12 weeks later (t + 12). Basal cortisol concentrations were lower at t + 5 or at t + 12 than at t + 0. Post stimulation mean cortisol concentrations were lower in males than in females at t + 5 (162 versus 232 nmol/l; P less than 0.05) but not at t + 0 (262 versus 320 nmol/l; P greater than 0.05) and t + 12 (188 versus 233 nmol/l; P greater than 0.05). These findings are indicating an increased susceptibility of bitches to environmental stress.

Plasma Cortisol Changes in Seawater-Adapted Mummichogs (Fundulus heteroclitus) Exposed to Ammonia

Seawater-adapted mummichogs (Fundulus heteroclitus) were exposed to total NH4-N concentrations of 1, 2, 5, 10, 25, 50, 100, 150, and 200 mg/L for periods of 2, 4, 8, 12, 18, 24, 36, and 48 h. Afterward, the fish were captured quickly and anesthetized with MS-222 before blood was collected. The concentration of total NH4-N and duration of exposure accounted for, respectively, ~35 and &lt;4% of the observed increase in plasma cortisol. The effective concentration (the concentration of total NH4-N inducing a mean cortisol response two standard deviations above the mean of the controls) was 47.14 mg/L, corresponding with a mean cortisol level of 13.44 μg/dL. Test concentrations of NH3-N were calculated from total NH4-N, pH, salinity, and temperature (constant at 20 °C), and the effects of both forms of ammonia on plasma cortisol concentration were compared. Significance was not detected at p &lt; 0.05, demonstrating that total NH4-N and NH3-N explained the observed changes in cortisol levels similarly. Mean cortisol concentrations of mummichogs anesthetized and sampled in the field were comparable with published values and did not differ significantly from the mean value of captive control fish sampled after the same length of time in MS-222 (p &lt; 0.05).

Multiple hormone responses to clonidine administration in depressed patients and healthy volunteers

Abnormalities in several hypothalamic-pituitary-target organ axes in depression may reflect alterations in central neurotransmitter receptor function. As the α 2-adrenergic receptor has been implicated in a variety of neuroendocrine abnormalities in depression, we assessed the role of α 2-adrenoceptor dysfunction in mediating response abnormalities of growth hormone, cortisol, and prolactin after intravenous clonidine administration (an α 2-adrenergic receptor agonist) in 18 patients with major depression (12 with melancholic features, 6 without melancholic symptoms) and 9 healthy volunteers. In particular, we examined the hypothesis that these abnormalities might be more evident in patients with DSM-III melancholic depression. After clonidine, the mean growth hormone response was significantly lower in melancholic depressives compared to controls ( p = 0.02), and the shape of the growth hormone response profile was also significantly different in melancholic patients ( p = 0.04). There was an overall decrease in the mean cortisol concentration after clonidine in melancholic patients and control subjects ( p = 0.02), as well as a larger cumulative prolactin response in melancholic patients compared to those without melancholic features ( p = 0.02). The present results confirm prior observations of a blunted growth hormone response after clonidine and suggest that alterations in α 2-adrenergic receptor activity might also contribute to several neuroen-docrine abnormalities in patients with melancholic depression.

Acute Inhibition of Gonadotropin Secretion by Corticotropin-Releasing Hormone in the Primate: Are the Adrenal Glands Involved?*

To investigate the role of the adrenal glands in the acute inhibition of gonadotropins induced by CRH in the primate, we have compared the effects of CRH infusion on LH and FSH before and after adrenalectomy and under variable glucocorticoid backgrounds. The studies were performed in four ovariectomized rhesus monkeys. Confirming previous observations, a 5-h iv CRH (rat/human CRH, 100-150 micrograms/h), but not saline, infusion inhibited both LH and FSH secretion. Saline and CRH infusions were repeated at random intervals after adrenalectomy under each of three different glucocorticoid backgrounds, achieved by varying the glucocorticoid replacement therapy (groups 1-3). At the time of the saline or CRH tests, mean cortisol concentrations were 38.5 +/- 6.3 (+/- SE) micrograms/dl before adrenalectomy, and 21.9 +/- 1.4, 14.3 +/- 1.1, and less than 1.0 micrograms/dl in groups 1, 2, and 3 of adrenalectomized (ADX) monkeys. In response to CRH infusion, gonadotropin concentrations significantly decreased in groups 2 and 3, but not in group 1 ADX monkeys which had the highest cortisol background. By hour 5 of CRH infusion, the percentages of the preinfusion baseline area under the curves for LH were 96.8 +/- 6.2%, 44.6 +/- 3.7%, and 53.5 +/- 6.1%, for groups 1, 2, and 3; by hour 4 the values for FSH were 95.7 +/- 3.5%, 76.2 +/- 4.7%, and 74.7 +/- 4.0% for groups 1-3, respectively. The absence of a response to CRH in group 1 animals occurred even though mean cortisol concentrations were lower than those in the same monkeys before ADX. Morphine (9 mg, iv), which had previously been shown to decrease LH and FSH concentrations in ovariectomized monkeys, also significantly decreased LH and FSH concentrations in ADX monkeys of group 1, which did not respond to CRH. The maximal decline occurred by hour 3 after morphine injection, when LH and FSH areas under the curve were 51.5 +/- 11.4% and 61.0 +/- 3.2% of the preinfusion baseline. Our results clearly indicate that in the primate the adrenal glands are not required for the acute CRH inhibitory effect on LH and FSH, and consequently, the decrease in gonadotropins that follows CRH is not mediated by the resultant increase in cortisol release, but, rather, by central mechanisms. The results also show that the effectiveness of CRH in inhibiting gonadotropins in the ADX monkey is affected by the amount of glucocorticoids present at the time of the test; unexpectedly, the ADX monkey is more sensitive to this protective effect of glucocorticoids than the non-ADX animal.

The effects of handling by humans at calving and during milking on the behaviour and milk cortisol concentrations of primiparous dairy cows

This study examined the effects of human presence at the time of calving of primiparous cows, and the behaviour of the stockperson during milking on the behaviour of the cows during milking and in response to an experimenter in a standard 5-min test (human test). Cows which were not handled around the time of their first calving ( n=7) displayed a higher ( P<0.05) number of flinch, step and kick (FSK) responses during the first 20 weeks of lactation than cows which were handled ( n=7); most of these FSK responses occurred in the close presence of the stockperson. It is of interest that although the two treatments did not differ in the amount of extra assistance given by the stockperson, the number of FSK responses of cows was strongly ( P<0.01) and positively correlated with the amount of extra assistance given by the stockperson in the form of attaching a kick-bar, replacing dislodged cups or steadying the cow by holding the tail or leg. Cows in the no handling treatment were also slower ( P<0.05) to enter areas within 1 and 2 m of the experimenter in the human test conducted in the sixth week of lactation and had higher ( P<0.05) mean cortisol concentrations in their milk than cows in the handling treatment. It is proposed that the lower FSK response of cows that received human contact at the time of their calving was a result of these cows being less fearful of humans. Although the two stockpersons differed significantly ( P<0.01) in the proportion of physical interactions which were negative (aversive) in nature that they directed towards cows, the stockpersons had no significant influence on the behaviour of the cows during milking. However, the number of physical interactions that the cow received that were of a positive nature was significantly ( P<0.05) correlated with the total number of FSK responses displayed in the first 2 weeks of lactation. It appears that stockpersons recognize those cows with a high FSK response and attempt to quieten them with the use of interactions that are positive in nature.

EFFECT OF STAGE OF LACTATION AND OF DAILY INJECTIONS OF GRF AND TRF ON SERUM CORTISOL IN LACTATING SOWS

Two experiments were conducted with 51 primiparous sows to determine the effects of stage of lactation and treatment with growth hormone-releasing factor (GRF) and thyrotropin-releasing factor (TRF) on serum cortisol concentrations and pulse profiles. Animals were injected with either saline, GRF (20 μg kg−1 in both experiments), TRF (1 μg kg−1 and 9 μg kg−1 in exps. 1 and 2, respectively) or GRF-TRF (administered in combination at the levels mentioned above). Peptides were given subcutaneously twice daily between days 5 and 25 postpartum. In exp. 1, mean cortisol levels were higher on day 5 than on subsequent sampling days due to higher peak amplitudes. This result is discussed with respect to stress. Mean serum cortisol concentrations did not vary significantly between days 5, 15 and 25 of lactation in exp. 2. No evidence of a morning peak and late afternoon low was observed in cortisol secretion of sows during lactation. Finally, none of the hypothalamic factor treatments altered the basal serum concentrations or the peak amplitudes of cortisol. However, in exp. 2, the frequency of cortisol peaks was lower for the GRF- and TRF-treated sows than for the control and GRF-TRF sows. Key words: Cortisol, GRF, TRF, lactation, sows

PREOPERATIVE INTERCOSTAL NERVE BLOCK: EFFECT ON THE ENDOCRINE METABOLIC RESPONSE TO SURGERY

The plasma cortisol and glucose responses to cholecystectomy were studied in 20 healthy patients. Ten patients received preoperative intercostal nerve blocks of the 6th to 12th nerves bilaterally using 0.5% bupivacaine with adrenaline 250 micrograms. The control group had the same quantity of adrenaline infiltrated into the intercostal space. Both groups had general anaesthesia with endotracheal intubation and controlled ventilation. In the non-blocked group, the mean cortisol concentration increased from a control value of 182.5 nmol litre-1 to a peak of 686.2 nmol litre-1 at 5.5 h after incision. In the blocked group the baseline serum cortisol concentration was 283.8 nmol litre-1 and it increased to a similar peak at 5.5 h. There were no significant differences between groups. The baseline plasma glucose concentration was also higher in the blocked group (4.45 mmol litre-1 compared with 3.94 mmol litre-1), but after a brief increase following the performance of the block decreased to only 14% above control values. The unblocked group exhibited substantial increase following the start of the surgery which continued for the duration of the study period to end at a mean of 6.48 mmol litre-1. These differences were significant (P less than 0.001). It is concluded that bilateral intercostal blocks may inhibit the glucose response to surgery, but have no effect on the cortisol response.

Effects of low dosages of intravenous dexamethasone on serum cortisol concentrations in the normal cat

The suppressive effects of three different low dosages of dexamethasone (5, 10 and 15 μg kg −1) on serum cortisol concentrations were evaluated in 10 normal cats. On four different days, serum was collected before and at two, four, six and eight hours after the intravenous administration of saline or dexamethasone. Following the administration of saline, no significant difference in mean serum cortisol concentrations was noted between the basal or post-injection values. In contrast, mean serum cortisol concentrations decreased significantly (P<0·05) by two hours and remained significantly below mean basal values eight hours after injection of all three dosages of dexamethasone. The degree of cortisol suppression became progressively greater as the dosages of dexamethasone were increased. After administration of the highest dose of dexamethasone (15 μg kg −1), serum cortisol decreased to below 5 ng ml −1 by two to four hours and remained suppressed (under 5 ng ml −1) eight hours after injection in all cats. In contrast, two of the 10 cats showed a slight escape from cortisol suppression by eight hours after injection of dexamethasone at the dosage of 10 Mg kg −1, whereas a dosage of 5 μg kg −1 failed to suppress cortisol concentrations below 10 ng ml −1 at any of the sampling times in one cat and was associated with increasing serum cortisol concentrations at eight hours after injection in three cats. The results of this study indicate that, of the three dosages of dexamethasone evaluated in this study, the 15 μg kg −1 dose may be the most reliable consistently to suppress serum cortisol to low or undetectable concentrations, as well as maintain such cortisol suppression at eight hours after injection in the normal cat.

Significance of the estriol profile as an endogenous function test of the fetoplacental unit

Oestriol profile represents a functional parameter of the foetal placental unit. Basing on the fact that maternal cortisol regulates oestriol production via a negative feedback action on foetal hypothalamus, relative low serum oestriol concentrations in the morning are compared with increasing oestriol concentrations in the evening, spaced out at short-time intervals, pointing to a dynamic oestriol production of the foetal placental unit. The mean oestriol concentration in the morning and maximum peak values in the evening were determined as criteria of the oestriol profile. In normal pregnancies (n = 74) the oestriol concentration in the morning increases from an average value of 8.0 ng/ml in the 32nd/33rd week to 11.6 ng/ml in the 40th/41st week of gestation. During the same period the peak values in the evening rise from 8.8 to 15.9 ng/ml. The mean cortisol concentrations in normal pregnancies (n = 49) from 32nd to 41st week are in the range of 333 +/- 88 ng/ml in the morning and 205 +/- 66 ng/ml in the evening. There is no significant difference between individual weeks. The predictive value of the oestriol profile was assessed regarding the foetal outcome of 55 high-risk pregnancies. 32 newborn infants exhibited intrauterine growth retardation with birth weights below the 10th and 5th percentile, respectively. In this group 6 patients exhibited low oestriol values in the morning, whereas 12 demonstrated a pathological profile in the evening. In 11 of 12 high-risk pregnancies exhibiting pathological oestriol profile growth, retardation of the newborn was found to be below the 5th percentile. Cortisol concentrations do not significantly differ between normal and high-risk pregnancies.(ABSTRACT TRUNCATED AT 250 WORDS)