Changes in pituitary responses to synthetic ovine corticotrophin releasing factor in fetal sheep

The rise in cortisol in fetal sheep during late pregnancy has been related to increased responsiveness of the adrenal to ACTH. Most reports have suggested that plasma ACTH concentrations rise coincident with or after the prepartum increase in cortisol. To reexamine the relationship of cortisol with basal immunoreactive ACTH (IR-ACTH) throughout the last 40 days of pregnancy and to determine changes in fetal pituitary responsiveness during this time, we measured basal and synthetic ovine corticotrophin-releasing factor (oCRF) (10 ng-10 micrograms) induced rises in ACTH and cortisol in fetal sheep at days 110-115, 125-130, and 135-140 of pregnancy. The fetuses were catheterized on day 105-120 and entered spontaneous labour at greater than 140 days. Basal IR-ACTH (picograms per millilitre +/- SEM) rose from 16.7 +/- 2.9 pg/mL at day 110-115 to 34.8 +/- 8.7 pg/mL at day 141-145. There was a significant effect of time on basal ACTH concentrations with a mean increase of approximately 5 pg ACTH per millilitre of plasma per 5-day sampling interval. Plasma cortisol changed gradually between day 110 and 125 of gestation and then more rapidly to term. At day 110-115 of gestation there was no significant change in plasma ACTH after 10 or 100 ng oCRF, but there was a significant increase in ACTH after 1 microgram of oCRF. Plasma cortisol did not change after any CRF injection. The change in IR-ACTH after oCRF at day 125-130 of gestation was significantly greater than that at day 110-115. Plasma cortisol concentrations were elevated following 1- and 10-micrograms injections of oCRF.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of estradiol on output of adrenocorticotropin and prolactin by fetal sheep anterior pituitary cells

We examined the hypothesis that estradiol (E2) would affect fetal anterior pituitary corticotroph and lactotroph function in vitro, and that any effects would be influenced by gestational age. Anterior pituitary cells from fetal sheep at day 129 (n = 4) and at day 139 (n = 5) of gestation were cultured. After 96 h in culture, cells were treated for 18 h with E2 concentrations ranging from 0 to 1000 nM, in the presence or absence of 100 nM of corticotropin-releasing hormone (CRH), cortisol, arginine vasopressin (AVP), or CRH and cortisol, to examine their effects on corticotroph function. Cells were also treated with bromocriptine or increasing concentrations of E2 to study their effects on lactotroph function. Immunoreactive (ir) adrenocorticotropin (ACTH) and prolactin in the culture medium were measured by radioimmunoassay. Levels of cellular pro-opiomelanocortin (POMC) mRNA and prolactin mRNA were determined by in situ hybridization. Immunohistochemistry was used to determine the percentage of cells that were immunopositive for ACTH (corticotrophs) or prolactin (lactotrophs). ACTH output was stimulated by CRH treatment at day 139 but not at day 129 of gestation, and cortisol attenuated this response. ACTH output by cells cultured with 10 nM E2 and 100 nM CRH, at 139 days of gestation, was greater than with CRH alone (p < 0.05). E2 did not affect basal ACTH output or ACTH output with any other treatment or levels of POMC mRNA. Prolactin output was not affected by E2 treatment. Bromocriptine significantly decreased prolactin output but not levels of prolactin mRNA. We conclude that E2 may affect CRH-stimulated fetal sheep pituitary corticotroph function late in gestation, but only within a narrow, physiological range of concentration.     

变压器噪声暴露对豚鼠应激、肝肾及免疫功能的影响

目的:探讨短时间内变压器噪声暴露对豚鼠应激、肝肾及免疫功能的影响。方法:取32只健康成年(5-6月龄)豚鼠随机分为实验组和对照组,每组16只。实验组给予录制的变压器噪声(声压级范围40.8-55 d B SPL,频谱范围150-2000 Hz)连续暴露28天,10小时/天(晚10点到早上8点),对照组在相同条件下饲养,无噪声暴露。噪声暴露结束后,对实验豚鼠的应激、肝肾及免疫功能进行定量评估比较。结果:噪声暴露28天后实验组豚鼠的应激状态指标(ACTH、血清皮质醇)与对照组比较差异无统计学意义(P0.05),主要肝肾功能指标与对照组比较差异无统计学意义(P0.05),免疫相关指标(Ig G、Ig A、Ig E、IL-1、IL-2)比较差异无统计学意义(P0.05)。结论:声压级范围为40.8-55 d B SPL、频谱范围为150~2000 Hz的变压器噪声连续暴露28天(10小时/天)对成年豚鼠应激、肝肾及免疫功能无明显影响。     

Prenatal betamethasone exposure results in pituitary-adrenal hyporesponsiveness in adult sheep

Fetal exposure to synthetic glucocorticoids in sheep results in increased fetal hypothalamic-pituitary-adrenal (HPA) activity persisting to one year of age. We aimed to determine the effects of single or repeated maternal or fetal betamethasone injections on offspring HPA activity at 2 and 3 yr of age and whether changes in adrenal mediators of steroidogenesis contribute to changes in pituitary-adrenal function. Pregnant ewes or their fetuses received either repeated intramuscular saline or betamethasone injections (0.5 mg/kg) at 104, 111, 118, and 124 days of gestation (dG) or a single betamethasone injection at 104 dG followed by saline at 111, 118, and 124 dG. Offspring were catheterized at 2 and 3 yr of age and given corticotrophin-releasing hormone + arginine vasopressin challenges. Adrenal tissue was collected for quantitative RT-PCR mRNA determination at 3.5 yr of age. In 2-yr-old offspring, maternal betamethasone injections did not alter basal ACTH or cortisol levels, but repeated injections elevated ACTH responses. At 3 yr of age, basal ACTH was elevated, and both basal and stimulated cortisol levels were suppressed by repeated maternal injections. Basal and stimulated cortisol-to-ACTH ratios and basal cortisol-to-cytochrome P-450 17alpha-hydroxylase (P450c17) mRNA ratios were suppressed by repeated injections. Repeated fetal betamethasone injections attenuated basal ACTH and cortisol levels in offspring at 2 but not 3 yr of age. Plasma changes were not associated with altered adrenal P450c17, ACTH receptor, beta-hydroxysteroid dehydrogenase, or glucocorticoid receptor mRNA levels. These data suggest that maternal, but not fetal, betamethasone administration results in adrenal suppression in adulthood.     

Plasma adrenocorticotropic hormone and cortisol in pigs: effects of time of day on basal and stressor-altered concentrations

An initial study was conducted to establish the presence in plasma of diurnal rhythms of immunoreactive porcine adrenocorticotropic hormone (pACTH) and cortisol in castrated male pigs (barrows). Fourteen barrows with jugular catheters were bled at 6-hr intervals for 24 hr. Significant changes in plasma pACTH were evident with peak levels (61 +/- 6 pg/ml) at 0100-0700 hr and a trough (38 +/- 4 pg/ml) at 1900 hr. Changes (P less than 0.05) in plasma cortisol were also present in barrows with a peak (44 +/- 6 ng/ml) at 0700 hr and a trough (21 +/- 5 ng/ml) at 1900 hr. Plasma norepinephrine and epinephrine were measured at the same time intervals and did not differ among hours. In these unstressed pigs the ratio cortisol/log10pACTH at 0700 hr (25.3 +/- 3.0) was greater than the ratio at 1900 hr (12.9 +/- 2.7). Sequential blood samples were subsequently taken on four of the barrows 12 and 26 days later. Plasma pACTH was variable among pigs and did not differ among hours. Plasma cortisol on both dates was greater (P less than 0.05) in the morning (0100 or 0700 hr) than at 1900 hr. The ratio cortisol/log10pACTH at 0700 hr was repeatedly greater than at 1900 hr. A second study was conducted to determine whether plasma pACTH and cortisol responses to mild (32 degrees C for 2 hr) or strong (20-min restraint) stressors were dependent on the time of day of stressor application (0800 hr, AM; 1600 hr, PM). Response-associated parameters (maximum concentration, maximum incremental concentration, and integrated response) for pACTH and cortisol did not differ between AM and PM. However, a qualitative difference existed between the AM and PM plasma pACTH responses to restraint +32 degrees C wherein the AM response consisted of a single prolonged surge, and the PM response of an initial major peak followed by a second significant minor peak. A suggested explanation is that the initial 20-min restraint stressor potentiated the hypothalamic-hypophyseal response to 32 degrees C. These studies are the first direct measurements which suggest the presence of diurnal changes in plasma ACTH and cortisol in barrows. The studies also indicate for barrows an absence of diurnal changes in plasma epinephrine and norepinephrine. The responsiveness of the pituitary-adrenocortical axis to stressors did not exhibit quantitative diurnal changes at the time periods measured. However, it is hypothesized that the repeatable AM-PM difference in the ratio cortisol/log10ACTH reflects a diurnal change in adrenal responsiveness to ACTH in unstressed pigs.     

Hormonal changes in spontaneous and aglépristone-induced parturition in dogs

To increase our understanding of the endocrine changes associated with parturition in dogs, plasma concentrations of progesterone (P4), 15-ketodihydroprostaglandin F(2alpha) (PGFM), estradiol-17-beta (E2beta), cortisol, ACTH, prolactin (PRL), LH, and FSH were measured in six spontaneously whelping bitches and in six bitches in which parturition was induced with the progesterone-receptor blocker aglépristone on day 58 of pregnancy. Expulsion of pups in the induced group took place in the presence of P4 concentrations that were still elevated. PGFM concentrations increased before parturition in both groups, but levels were lower in the induced bitches. PGFM levels reached a maximum in both groups during parturition and quickly decreased in the spontaneously whelping group after parturition, but remained elevated in the induced group. In both groups, cortisol concentrations reached similar maximum levels during the last 30 h before the onset of expulsion. During the 3 days postpartum, cortisol concentrations were higher in the induced group. The highly variable ACTH concentrations did not differ significantly throughout the study within or between groups. In both groups, E2beta concentrations decreased and PRL concentrations increased between the late gestational period and the 30-h period before parturition. Concentrations of both LH (spontaneously whelping group) and FSH (both groups) decreased between late gestation and the postpartum period. The results of this study illustrate the hormonal changes around parturition in the bitch, and reveal that aglépristone-induced parturition is associated with still incomplete luteolysis, an altered PGFM profile, and elevated postpartum cortisol concentrations as compared with spontaneously whelping dogs.     

Effects of nighttime low frequency noise on the cortisol response to awakening and subjective sleep quality

The effects of night-time exposure to traffic noise (TN) or low frequency noise (LFN) on the cortisol awakening response and subjective sleep quality were determined. Twelve male subjects slept for five consecutive nights in a noise-sleep laboratory. After one night of acclimatisation and one reference night, subjects were exposed to either TN (35dB L(Aeq), 50dB L(Amax)) or LFN (40dB L(Aeq)) on alternating nights (with an additional reference night in between). Salivary free cortisol concentration was determined in saliva samples taken immediately at awakening and at three 15-minute intervals after awakening. The subjects completed questionnaires on mood and sleep quality. The awakening cortisol response on the reference nights showed a normal cortisol pattern. A significant interaction between night time exposure and time was found for the cortisol response upon awakening. The awakening cortisol response following exposure to LFN was attenuated at 30 minutes after awakening. Subjects took longer to fall asleep during exposure to LFN. Exposure to TN induced greater irritation. Cortisol levels at 30 minutes after awakening were related to "activity" and "pleasantness" in the morning after exposure to LFN. Cortisol levels 30 minutes after awakening were related to sleep quality after exposure to TN. This study thus showed that night time exposure to LFN may affect the cortisol response upon wake up and that lower cortisol levels after awakening were associated with subjective reports of lower sleep quality and mood.     

Cytochemical bioassay and radioimmunoassay of ACTH in noise stressed rats.

Serum corticosterone and ACTH levels were measured in rats subjected to one and two 30 min intervals of noise (100 dB, 250--20,000 Hz). Both hormones were elevated immediately after noise exposure, dropped below pre-exposure levels after a 2 hr recovery interval and were again elevated with a second exposure. The ratio of immunoactive to bioactive ACTH was slightly depressed after one exposure and markedly depressed after two successive noise exposures (relative to controls) indicating that multiple exposure to auditory stimulation effects a proportionally greater output of bioactive ACTH.     

Effects of corticotropin-releasing hormone on ACTH, cortisol and 13,14-dihydro-15-keto prostaglandin E2 in patients with diabetes insipidus before and after captopril treatment

A corticotropin-releasing hormone (CRH) test was performed on 7 patients with central diabetes insipidus (DI) and on 7 healthy subjects. The test was repeated on the patients with DI after 3 days of oral treatment with captopril at a dose of 100 mg daily. No significant difference in the responses of plasma ACTH and cortisol to CRH between the patients and the controls was found. The short-term captopril treatment resulted in a significant decrease of both basal and CRH-stimulated ACTH and cortisol levels in the patients with DI. CRH did not induce any changes in the stable metabolite of prostaglandin E₂ 13,14-dihydro-15-keto-prostaglandin E₂ (PGE₂-M) in the patients with DI before or after the captopril treatment. The results obtained suggest that vasopressin is not an obligatory factor for a normal ACTH response to CRH. Angiotensin II (A II) is involved in the regulation of ACTH. This study confirmed our previous data showing the lack of any specific effect of CRH on PGE₂ production.     

Behavioral and other systemic effects of cortisol-21 sulfate

Three milligrams of cortisol-21 -sulfate or cortisol free alcohol in oil suspension was administered intramuscularly to male rats on alternate days for 2–7 weeks. Open-field tests repeated at 2- or 3-day intervals revealed that both steroids had significant stimulatory effects on the animal's exploratory behaviors (ambulation and rearing), when the treatments were started soon after weaning (postnatal day 21–24). The same treatments to adult rats (46 days old), however, did not cause any change in the activity levels. It was also shown that cortisol sulfate, in contrast to free cortisol, was inert as a glucocorticoid; it had no catabolic, gluconeogenic, lympholytic, or ACTH-suppressive effects. The results suggest that cortisol sulfate, and probably free cortisol as well, affects behavior through its direct action on the central nervous system rather than via its effects on intermediary metabolism or negative feedback on pituitary ACTH release.     

Repeated administrations of adrenocorticotropic hormone during late gestation in pigs: maternal cortisol response and effects on fetal HPA axis and brain neurotransmitter systems

The present study examined the effects of repeated adrenocorticotropic hormone (ACTH) administrations to sows during late gestation on hypothalamic-pituitary-adrenocortical (HPA) axis and brain neurotransmitter systems in their fetuses. ACTH (100 IU per animal, Synacthen Depot, n=6) or saline (n=5) was administered intramuscularly to sows every 2nd day from gestational day (GD) 85 to GD 101. Blood samples were taken from sows repeatedly within 12h after ACTH application on GD 85 and GD 101. On GD 105, fetuses were recovered under general anaesthesia for the collection of blood and brain samples. Plasma cortisol concentrations in sows increased significantly within 2h after ACTH application and returned to control levels after 10h post-application, showing a similar response at the beginning and at the end of the 16-day stimulation period. On GD 101, a significant increase of plasma glucose and insulin concentrations was found in sows after administration of ACTH and after a following feeding time. Number and body weight of fetuses were not affected by the maternal ACTH treatment. Cortisol concentrations in the umbilical vein were significantly decreased in fetuses from ACTH sows and a similar trend was observed in the umbilical artery and in the vena cava cranialis. Glucocorticoid receptor (GR) binding in hippocampus and hypothalamus did not differ between treatments. However, in hippocampus, serotonergic activity was increased in fetuses from ACTH-treated mothers as shown by significantly elevated 5-hydroxytryptamine (5-HT) levels. In conclusion, repeated administrations of ACTH during late gestation resulted in a reproducible cortisol response of sows and reduced cortisol concentrations in the fetal umbilical vein after the treatment period. Although the number of sows used in this experiment was low and differences between treatments were limited these findings indicate that excessive glucocorticoid exposure during gestation alters serotonergic activity in hippocampus of fetuses and may affect the emotional reactivity later in life.     

Effects of adrenocorticotropin stimulation on cortisol dynamics of pregnant gilts and their fetuses: implications for prenatal stress studies

The effect of adrenocorticotropic hormone (ACTH) administration on plasma cortisol concentrations was determined in pregnant gilts and their fetuses. In a first experiment, 100 IU ACTH (Synacthen Depot) was administered intramuscularly to the gilts every second day from Days 49 to 75 of gestation. ACTH injections were carried out at 08:00 h and, thereafter, 10 blood samples were taken within the following 8h via jugular catheters. Blood samples were analysed for plasma cortisol concentrations, and results were compared with values from animals which were treated with physiological saline and untreated animals (blood sampling only). The values for plasma cortisol concentrations increased until 3h after ACTH applications to a mean maximum level of 276.5+/-17.2 nmol/l in the whole 4-week stimulation period. Plasma cortisol levels did not return to pre-treatment values within the 8 h post-injection. No differences in cortisol levels were found between the physiological saline and untreated control, and no habituation of the adrenocortical response to ACTH was found during the 4-week stimulation period. In a second experiment, 100 IU ACTH were administered to pregnant gilts at gestation Day 65. After 3 h, fetuses were recovered under general anaesthesia and blood samples were taken from the umbilical vein, artery, and, after decapitation, from periphery. Application of ACTH to the sows significantly increased their plasma cortisol concentrations (P<0.001), and also increased plasma cortisol concentrations in peripheral blood samples from the fetuses (P=0.09) and in the umbilical vein (P<0.001) and artery (P<0.01), respectively. Plasma ACTH concentrations did not differ in fetuses from ACTH-treated or control sows. The results show that in gilts the adrenocortical response to an exogenous application of Synacthen Depot is consistent over time during mid-gestation. Furthermore, cortisol but not ACTH levels were increased in fetuses from ACTH-treated sows, indicating that maternal cortisol can cross the placenta during mid-gestation. The stimulation of maternal cortisol release through exogenous ACTH with subsequent elevation of fetal cortisol levels is, therefore, a useful approach for studying effects of elevated maternal glucocorticoids in prenatal stress studies in pigs.     

Diurnal patterns of testosterone, dihydrotestosterone, estradiol, and cortisol in serum of rhesus males: Relationship to sexual behavior in aging males

This study was carried out to determine differences between old and young rhesus males in levels and diurnal patterns of testosterone, dihydrotestosterone, cortisol, and estradiol, and to determine correlations between these hormones and sexual behavior of the old males. Blood was drawn from old (n = 9) and young (n = 9) rhesus males over 5 consecutive days at 0900, 1300, and 2100 hr. The two groups of males did not differ in mean serum levels of testosterone, dihydrotestosterone, or estradiol at any time. Although the old and young did not differ in cortisol levels at 0900 and 1300 hr, the cortisol levels at 2100 hr were lower in the old males. Diurnal variations in testosterone, dihydrotestosterone, and cortisol were comparable in old and young males. Mean serum levels of estradiol were significantly higher at 0900 hr than at 1300 hr in the old males, whereas in the young males estradiol levels did not differ with time of day. There was a significant positive correlation between testosterone and yawning rate, and cortisol levels were correlated positively with rate of contacting, rate of mounting, and percentage of tests with erections. The decline in sexual performance of old rhesus males cannot be attributed to changes in the levels or diurnal patterns of testosterone, dihydrotestosterone, or estradiol, but lower cortisol levels in old males may contribute to the decline in sexual behavior.     

Noninvasive monitoring of fecal cortisol metabolites in the eastern chipmunk (Tamias striatus): validation and comparison of two enzyme immunoassays

Monitoring fecal glucocorticoid metabolites in wild animals, using enzyme immunoassays, enables the study of endocrinological patterns relevant to ecology and evolution. While some researchers use antibodies against the parent hormone (which is typically absent from fecal samples), others advocate the use of antibodies designed to detect glucocorticoid metabolites. We validated two assays to monitor fecal cortisol metabolites in the eastern chipmunk (Tamias striatus). We compared an antibody produced against cortisol and one produced against 5α-pregnane-3β, 11β, 21-triol-20-one using a radiometabolism study and an injection with adrenocorticotropic hormone (ACTH). Most cortisol metabolites were excreted in the urine (～83%). Peak excretion in the feces occurred 8 h after injection. Both assays detected an increase in fecal cortisol metabolite levels after injection of ACTH. Males, but not females, exhibited a circadian variation in metabolite levels. The sexes did not exhibit any difference over the time course and route of excretion or the relative increase in fecal cortisol metabolite levels after ACTH injection. The cortisol assay displayed higher reactivity to ACTH injection relative to baseline than did the metabolite assay. While both antibodies gave comparable results, the cortisol antibody was more sensitive to changes in plasma cortisol levels in eastern chipmunks.     

Effects of adrenocorticotrophin (ACTH) and progesterone on luteinising hormone (LH) secretion in recently castrated rams.

The goal of the present study was to determine whether ACTH and progesterone have any effect on LH secretion and pulse frequency in recently castrated rams. Six 2-year-old Corriedale rams were castrated in the winter. The day before castration, blood samples were taken in order to establish the precastration LH levels. The rams were divided into an untreated group (group U: n = 2) and a treated group (group T: n = 4). The first treatment consisted of the i.v. administration of 0.5 mg of ACTH on day 20 post-castration, immediately after the first sample had been taken. During the second treatment, subcutaneous progesterone implants were given to group T for 5 days. Control samplings were performed one week before each treatment. Prior to castration, the testosterone levels were low, while after castration they were below the detection limit of the assay. Cortisol and progesterone concentrations were basal before castration in all of the animals and after castration in group U and also in the control samplings for group T. ACTH treatment caused a significant increase in both cortisol and progesterone levels for 3 h (P < 0.001). Progesterone implants raised progesterone levels in group T, but cortisol levels remained basal. Before castration, all animals had low LH levels and hardly any pulse activity was seen. After castration, both the number of LH pulses and the mean LH production increased significantly in all of the animals (P < 0.01). During the ACTH trial, LH pulse frequency was significantly reduced for the first 4 h following ACTH administration (P = 0.013), however, no such differences occurred in the prior control period. No effect was seen on mean LH concentration during the ACTH treatment. Progesterone treatment did not have any effect on either the number of LH pulses nor on LH concentrations (P > 0.05).     

Baseline,diurnal variations,and stress-induced changes of stress hormones in three captive beluga whales,Delphinapterus leucas

Concentrations of plasma adrenocorticotropic hormone (ACTH), cortisol, and aldosterone were investigated in three adult beluga whales (Delphinapterus leucas), held in a large outdoor public aquarium exhibit. The purpose of this study was to evaluate resting concentrations of these hormones and associated diurnal variations with routine interactions and medical procedures. Resting blood samples were collected voluntarily from the ventral fluke veins at predetermined times of the day to evaluate diurnal changes in analyte concentrations. In addition, hematology and serum chemistry analyses were performed to monitor health status and evaluate changes related to physical exam procedures. Analogous sampling was conducted during out-of-water physical examinations and before and after wading-contact sessions (WCS). Baseline stress hormone concentrations (± SD) were as follows: plasma ACTH (8.41 ± 5.8 pg/mL), serum cortisol (1.80 ± 0.71 g/dL), and serum aldosterone (11.42 ± 5.5 pg/mL). Plasma ACTH and cortisol concentrations were consistently higher in early morning than evening, while aldosterone was higher in the evening. All stress-related hormones were significantly elevated during physical examination. Plasma ACTH concentrations were most increased, 5–10-fold, during physical examination, whereas cortisol and aldosterone showed 2–4-fold elevations. Stress response analytes measured during the WCS did not differ significantly from baseline concentrations.     

Plasma acth and cortisol levels in depressed patients: Relation to dexamethasone suppression test

Blood samples collected from normal subjects and newly hospitalized depressed patients at 8 AM on the day before and at 8 AM and 4 PM the day after receiving dexamethasone, 1 mg orally at 11 PM, were analyzed for ACTH and cortisol. The mean plasma ACTH values of these two groups were not significantly different at any of the times, while the cortisol levels of the depressed patients were significantly higher than those of the normal subjects at 8 AM pre-dexamethasone (P<0.001). There was no correlation between plasma ACTH and cortisol values in either group. The cortisol responses to dexamethasone in depressed patients revealed two subgroups. In one subgroup, the cortisol was suppressed as much as in normal subjects, but in the other, cortisol levels were not suppressed. The post-dexamethasone ACTH rebounded at 4 PM in the latter subgroup to higher values than in the subgroup with suppressed cortisol levels and in the normal subjects. After dexamethasone, the ACTH values were negatively correlated with plasma cortisol only in the normal subjects (P<0.01), not in the depressed patients. These results indicate that ACTH levels do not account for the elevated cortisol and the failure of dexamethasone to suppress cortisol levels in some depressed patients.     

Regulation of maternal ACTH in ovine pregnancy: does progesterone play a role?

Pregnancy is characterized by increased plasma adrenocorticotropic hormone (ACTH) and cortisol. Studies suggest that progesterone acts as an antagonist at mineralocorticoid receptors. Therefore, we tested the hypothesis that chronic progesterone, produced by treatment of nonpregnant ewes or during pregnancy, will result in increased plasma ACTH relative to the plasma cortisol concentrations. We studied three groups of ewes: ovariectomized nonpregnant, nonpregnant treated with progesterone, and pregnant ewes. In two series of studies, ewes were adrenalectomized and replaced with 0.35 mg x kg(-1) x day(-1) or 0.5 mg x kg(-1) x day(-1) cortisol. In both studies, aldosterone was infused at 3 microg x kg(-1) x day(-1). In the first study, additional infusions of cortisol over 24 h were used to increase daily replacement doses to 0.5, 1, or 1.5 mg x kg(-1) x day(-1), and intact pregnant and nonpregnant ewes were studied with infusions of cortisol at 0, 0.5, and 1 mg x kg(-1) x day(-1). In adrenalectomized ewes chronically replaced to 0.35 mg x kg(-1) x day(-1) cortisol, plasma ACTH concentrations were decreased significantly in the nonpregnant progesterone-treated ewes compared with the ovariectomized nonpregnant ewes. With 0.5 mg x kg(-1) x day(-1) cortisol, plasma ACTH levels were greater in pregnant ewes than in nonpregnant ewes with or without progesterone. Overall plasma ACTH levels at 0.35 mg x kg(-1) x day(-1) were significantly related to the plasma protein concentration, suggesting that the ACTH levels in the hypocorticoid ewes are most closely related to plasma volume. Across all steroid doses, ACTH was positively related to plasma proteins and progesterone, and negatively related to cortisol. We conclude that increased progesterone does not alter the feedback relation of cortisol to ACTH, but may modulate ACTH indirectly through plasma volume.     

Oral cadmium exposure throughout puberty does not inhibit secretion of prolactin, GH and ACTH through dopamine metabolism changes in male rat

This work analyzed possible dopamine-mediated cadmium effects on plasma prolactin, GH and ACTH levels and if these changes were related to metal accumulation. Male rats were treated from day 30 to 60 of life with 50 mg/L of CdCl₂ in the drinking water. Cadmium exposure decreased the dopamine (DA) metabolism (DOPAC/DA ratio) in all brain areas studied, and plasma levels of prolactin, GH and ACTH were diminished. The cadmium concentration did not increase nor in hypothalamus nor in the pituitary after the metal exposure. These results suggest that cadmium inhibits the secretion of these pituitary hormones and this inhibitory effect is not mediated by dopamine or the degree of metal accumulation.     

Changes in the levels of ACTH and cortisol after passive exposure to cigarette smoke in smokers and non-smokers

Plasma ACTH and cortisol levels were studied in smokers and non smokers, (exposed or not to smoke of the environment), after passive exposure to cigarette smoking. Non smokers, usually not exposed to smoke, show a rise in both hormones, whereas smokers and non smokers commonly exposed to smoke don't show any change in ACTH and cortisol levels. These data suggest that nicotine acts as an acute stimulus on the hypophysis-adrenal axis even passively inhaled.