Serum cortisol radioimmunoassay values in the normal ferret and response to ACTH stimulation and dexamethasone suppression tests

Cortisol values were obtained from 39 ferrets, Mustela putorius furo, by using a commercial radioimmunoassay. Sera from 25 males (18 intact, 7 neutered) and 14 females (7 intact, 7 spayed) were assayed. Resting serum cortisol values ranged from 0.13 to 2.70 micrograms/dl for males (mean = 0.93 +/- 0.63 micrograms/dl), and 0.55 to 1.84 micrograms/dl for females (mean = 0.86 +/- 0.29 microgram/dl). The resting cortisol values of both males and females were comparable to those of the cat (1.0 to 3.0 micrograms/dl). A 7 year old male ferret with suspected hyperadrenocorticism and an adrenal mass had a cortisol level of 8.1 micrograms/dl. Adrenal cortical carcinoma was the histologic diagnosis. One adult female ferret had a cortisol level of 3.30 micrograms/dl. This animal also had proliferative colitis upon necropsy. An ACTH stimulation test (1 U/kg IM) and a low-dose dexamethasone suppression test (0.1 mg/kg) were performed on 10 ferrets. Post-ACTH serum cortisol levels increased by an average of 89%. Post-dexamethasone serum cortisol values decreased by an average of 18% 6 hours post-injection.     

In vivo and in vitro studies on the effect of adrenocorticotropic hormone or cortisol on the pituitary response to gonadotropin releasing hormone

Experiment I: Hyperadrenal states were induced in intact heifers (N = 3) or adrenalectomized (ADRX) heifers (N = 3) by constant infusion of ACTH (20.8 micrograms, 1-24 ACTH/h) or hydrocortisone succinate (HS) (30 mg/h), respectively. Control infusions consisted of the saline vehicle. All infusions began on Day 2 of a normal estrous cycle. Exogenous gonadotropin releasing hormone (GnRH) was given as a 100-micrograms bolus i.v. on Days 7, 9, and 11 (intact) or 5, 7, and 9 (ADRX) of the cycle. In intact heifers, the cumulative luteinizing hormone (LH) response was reduced (P less than 0.05) by the ACTH treatment. In ADRX heifers, the HS treatment did not alter the cumulative response but did alter the qualitative response with a time X treatment interaction (P less than 0.01). The LH response in the HS-ADRX animals had a slower onset and lower peak concentrations with a more prolonged response. Experiment II: Dispersed bovine pituitary cells were prepared and incubated at concentrations of 2 X 10(6) viable cells in 2.0 ml per dish. Cells were exposed to cortisol at concentrations of 0.01, 0.10, 0.21 and 1.03 X 10(-6) M for time periods of 8, 14, 20 or 26 h for basal LH secretion studies and 10, 16, 22 and 28 h for GnRH-stimulated LH secretion. Both dosage of cortisol and length of exposure had a depressing effect on basal LH release. The cortisol pretreatment also decreased (P less than 0.001) the LH release following addition of GnRH (8.5 X 10(-8) M) in cultures at all dosages and exposure times of cortisol. However, there was no decrease in LH or protein content of cells. These experiments indicate a direct action of cortisol on the pituitary gland to depress both basal and stimulated LH release.     

Effect of ACTH (tetracosactide) on steroid hormone levels in the mare. Part B: effect in ovariectomized mares (including estrous behavior)

The mare is the only non-primate species known to display estrous signs after ovariectomy and adrenal hormones have been implicated as a possible cause. Moreover, in several species, estradiol seems to have a stimulatory effect on the hypothalamic-pituitary-adrenal axis. The aim of the present study was to compare the effect of ACTH (tetracosactide) on pertinent hormones [cortisol, progesterone, androstenedione, testosterone (intact and ovariectomized mares) and estradiol (ovariectomized mares only)] in intact mares in estrus with the same mares after ovariectomy (n=5). Blood samples were collected hourly from 12:00 until 14:00 h the following day (half-hourly between 14:00 and 17:00 h) on two occasions, with saline or ACTH treatment at 14:00 h (saline treatment day or ACTH treatment day). The mares, both when intact and after ovariectomy, showed a significant increase in all measured hormones, except estradiol (not measured in intact mares), after ACTH treatment, lasting at least 3h post-treatment (P<0.001). On the saline treatment day, cortisol levels in ovariectomized mares were lower than in intact mares in the evening (18:00-23:00 h), but higher at night (24:00-05:00 h). No differences in cortisol response between mares, when intact and after ovariectomy, were found after ACTH treatment (P=0.3). Androstenedione levels were lower (P<0.001) and increased less after ACTH treatment in ovariectomized mares, as compared to when intact (P<0.05). Progesterone concentrations were lower in the ovariectomized mares at night (24:00-05:00 h) on the saline treatment day and at all times on the ACTH treatment day (P<0.05). Testosterone concentrations were lower in ovariectomized mares on both treatment days, as compared to when intact (P<0.001). It was concluded that ovariectomy affected basal cortisol pattern. Ovarian androstenedione and testosterone contributed to the basal circulating levels and, in the case of androstenedione, was stimulated by ACTH. Endogenous estradiol did not act stimulatory on adrenal gland hormone production in the mare.     

Ability of cortisol and progesterone to mediate the stimulatory effect of adrenocorticotropic hormone upon testosterone production by the porcine testis

The influence of corticosteroids and progesterone upon porcine testicular testosterone production was investigated by administration of exogenous adrenocorticotropic hormone (ACTH), cortisol and progesterone, and by applying a specific stressor. Synthetic ACTH (10 micrograms/kg BW) increased (P less than 0.01) peripheral concentrations of testosterone to peak levels of 5.58 +/- 0.74 ng/ml by 90 min but had no effect upon levels of luteinizing hormone (LH). Concentrations of corticosteroids and progesterone also increased (P less than 0.01) to peak levels of 162.26 +/- 25.61 and 8.49 +/- 1.00 ng/ml by 135 and 90 min, respectively. Exogenous cortisol (1.5 mg X three doses every 5 min) had no effect upon circulating levels of either testosterone or LH, although peripheral concentrations of corticosteroids were elevated (P less than 0.01) to peak levels of 263.57 +/- 35.03 ng/ml by 10 min after first injection. Exogenous progesterone (50 micrograms X three doses every 5 min) had no effect upon circulating levels of either testosterone or LH, although concentrations of progesterone were elevated (P less than 0.01) to peak levels of 17.17 +/- 1.5 ng/ml by 15 min after first injection. Application of an acute stressor for 5 min increased (P less than 0.05) concentrations of corticosteroids and progesterone to peak levels of 121.32 +/- 12.63 and 1.87 +/- 0.29 ng/ml by 10 and 15 min, respectively. However, concentrations of testosterone were not significantly affected (P greater than 0.10). These results indicate that the increase in testicular testosterone production which occurs in boars following ACTH administration is not mediated by either cortisol or progesterone.     

Effect of ACTH (tetracosactide) on steroid hormone levels in the mare. Part A: effect in intact normal mares and mares with possible estrous related behavioral abnormalities

Ovariectomized mares and mares with inactive ovaries may show signs of estrus. The reason behind this phenomenon is not clear; however, steroid hormones of adrenal origin have been suggested. Moreover, aberrant adrenal hormone production has been implied as a reason why some intact mares may change behavior. In the present study, the effect of ACTH on plasma levels of cortisol, progesterone, androstenedione and testosterone was investigated in intact mares with normal estrous behavior ('controls', n=5) and intact mares that according to their owners showed deviant estrous behavior ('problem' mares, n=7). Blood samples were collected hourly from 12:00 h until 14:00 h the following day (half-hourly between 14:00 and 17:00 h) on two occasions (at two estruses), with saline or ACTH treatment (tetracosactide) at 14:00 h (saline treatment day or ACTH treatment day). ACTH treatment caused a significant increase in plasma levels of cortisol, progesterone, androstenedione and testosterone in all mares (P<0.05). An overall significant difference in cortisol response to ACTH was found (P<0.05), with 'problem' mares showing a significantly lower increase in cortisol levels 30 min to 3h post ACTH treatment (P<0.001). The 'problem' mares also showed a significantly higher increase than controls in progesterone levels in the same time period (P<0.05). The reason for the reduced adreno-cortical reactivity, with a low cortisol response to the ACTH treatment, in the 'problem' mares is unknown, but may indicate a difference in adrenal function as compared to control mares.     

Effects of hyperadrenal states on luteinizing hormone in cattle

The effect of an induced hyperadrenal state on luteinizing hormone (LH) secretion and subsequent ovarian function was examined in both intact and adrenalectomized (ADRX) heifers. Treatments were begun on Day 2 or Day 16 of an estrous cycle in order to examine their effect on corpus luteum development or ovulation, respectively. In Experiment I, continuous intravenous infusion of ACTH (1.0 mg/24 h) to intact heifers decreased LH concentrations during the early phase of the cycle (Days 3-5). Treatment of ADRX heifers with hydrocortisone succinate (HS) (100 mg/24 h) did not appear to change mean LH concentrations, although da Rosa and Wagner (1981) have reported reduced plasma concentrations of progesterone at mid-cycle in these ACTH-treated intact heifers and HS-treated ADRX heifers. ACTH treatment of ADRX heifers had no effect on LH or progesterone. In the second study, there were similar frequencies of LH surges at the anticipated time of ovulation in all treatment groups. HS (100 mg/24 h) in ADRX heifers and ACTH (0.5 mg/24 h) in intact heifers was given continuously beginning on Day 16 of an estrous cycle. Although some animals in all groups exhibited LH surges, the ACTH-treated intact and HS-treated ADRX heifers failed to show a consistent subsequent increase in progesterone concentrations in plasma, suggesting a failure of luteal development. Although no difference was seen in baseline concentrations of LH, there was a greater difference between basal and overall mean LH concentrations in control groups than was observed in ACTH- or HS-treated animals. These induced hyperadrenal states resulted in depression of ovarian function as shown by decreased plasma progesterone during the luteal phase of the cycle. It is not known if other noncorticoid steroids from the adrenal cortex are necessary for a full expression of this effect.     

The effect of ACTH stimulation on cortisol and progesterone concentrations in intact and ovariohysterectomized domestic cats

The objective was to evaluate the adrenocortical capacity for cortisol and progesterone production in female cats, both while intact and after ovariohysterectomy. Five privately owned female cats, 1-3 years old, were used in two trials while intact at an inactive stage of the cycle, and again in two trials, 2 weeks after ovariohysterectomy. The four trials were: intact saline injection control trial; intact ACTH injection (0.125 mg); ovariohysterectomized saline injection control trial; and ovariohysterectomized ACTH injection. Blood samples were obtained by an indwelling cephalic vein catheter at -30 and 0 min (immediately before injections) and at 60, 90, 120 and 180 min after injection. The mean basal pre-treatment concentrations of cortisol in the intact and ovariohysterectomized cats were 33 +/- 19 and 32 +/- 19 nmol/L, respectively; the corresponding values for progesterone were 1.1 +/- 0.6 and 0.7 +/- 0.6 nmol/L, respectively. Saline did not alter the serum cortisol or progesterone concentrations. In contrast, both cortisol and progesterone were elevated after ACTH, with peak values at 90 min and returned to basal levels at approximately 180 min. There was a positive correlation between cortisol and progesterone concentrations (r = 0.8, P < 0.05). In some instances, the procedure used to restrain the cats during blood collection induced increases in cortisol and progesterone of the same magnitude as when the ACTH was administered; these effects of restraint could alter the results of assisted reproduction efforts.     

Serum luteinizing hormone, 13,14-dihydro-15-keto-prostaglandin F2alpha and cortisol profiles during postpartum anestrus in Brahman and Angus cows

Pluriparous suckled Brahman and Angus cows were utilized to evaluate the effect of breed, day after calving and endogenous opioid peptides (EOP) on hormonal profiles during postpartum anestrus. On Days 17 and 34 after calving, blood samples with and without heparin were collected at 15- and 30-min intervals, respectively, for a 7-h period via jugular cannula. Two hours after the start of blood sampling, cows of each breed were administered either 1 mg/kg iv naloxone or saline. Three hours later, all animals received 10 ng/kg iv GnRH. On Day 34 after calving cows received 0.2 IU/kg iv ACTH. Mean LH, basal LH and area under the LH curve increased (P < 0.01) from Day 17 to Day 34 after calving. Height of LH pulses increased (P < 0.05) by Day 34 after calving. Brahman cows had higher (P < 0.05) mean LH, basal LH, LH pulse frequency and area under the LH curve than Angus cows. Naloxone increased postchallenge area under the LH curve in treated cows above that of control cows (P < 0.06). Naloxone also increased the postchallenge area under the LH curve above that of the prechallenge level (P < 0.01). No breed differences in the response to the naloxone challenge were observed. The LH response to naloxone challenge occurred earlier on Day 34 than on Day 17 after calving but the amount of LH released was similar between days. The GnRH-induced LH release was greater in Brahman than in Angus cows (P < 0.04). Mean cortisol concentrations and area under the cortisol curve decreased (P < 0.05) between Day 17 and Day 34 after calving. Mean cortisol concentrations and area under the cortisol curve were lower (P < 0.01) in Brahman than in Angus cows. Cortisol secretion after ACTH treatment was similar between Brahman and Angus cows. The cortisol response after ACTH challenge was positively correlated (r=0.68; P < 0.001) to the prechallenge area under the cortisol curve. Under optimal environmental conditions Brahman cows have a greater LH release and their anterior hypophysis is more sensitive to GnRH challenge than the Angus cows.     

Plasma ACTH, cortisol and aldosterone concentrations in chronically cannulated ovine fetuses and in lambs injected with ovine corticotropin releasing factor

Synthetic oCRF was intravenously injected into 3 groups of 5 chronically cannulated ovine fetuses in utero on days 120, 130 and 137 of gestation (10 micrograms/fetus). The respective twin fetuses were used as controls. Ovine CRF was also intravenously injected into 4 groups of 6 lambs on days 1, 3, 7 and 20 after birth (5 micrograms/kg bw). Fetal plasma ACTH and cortisol concentrations increased significantly following oCRF as early as 120 days of gestation without changing maternal plasma cortisol concentrations. The ACTH and cortisol response to CRF increased gradually on stages 130 and 137 of gestation, but on the other hand, plasma aldosterone did not change. In newborns, after oCRF, the pituitary response gave peak values at 10 min for plasma ACTH and adrenal response gave peak values at 15 min for plasma cortisol. Between 1 and 20 days, plasma ACTH and cortisol changes after oCRF decreased in older animals while aldosterone level remained unchanged. In animals receiving both treatments on days 1 and 20, plasma cortisol levels were increased for longer than in animals treated once.     

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)     

Serum concentrations of deoxycorticosterone in women during the luteal phase of the ovarian cycle are not suppressed by dexamethasone treatment

We determined the serum levels of deoxycorticosterone (DOC) in plasma of six healthy, apparently ovulatory women during the mid-follicular and mid-luteal phases of their ovarian cycles; and we evaluated the effect of dexamethasone (1 mg by mouth) on the concentrations of DOC and cortisol in serum at times when plasma progesterone levels were high or low. The serum levels of DOC, unlike those of cortisol, did not vary significantly in single blood samples obtained in the morning (8-10 a.m.) and afternoon (3-5 p.m.); and serum DOC levels in women were significantly higher (P less than 0.05) during the mid-luteal phase than during the mid-follicular phase of the cycle. There were unmistakable diurnal variations in serum levels of cortisol, and cortisol concentrations were reduced to less than 20% of pretreatment levels after the ingestion of 1 mg dexamethasone during the mid-follicular or mid-luteal phase. The serum concentrations of DOC were reduced only to approx 70% of pretreatment levels after dexamethasone ingestion during the follicular phase. The serum levels of DOC did not decline significantly after administration of dexamethasone during the mid-luteal phase, when progesterone levels in serum are high (14-16 ng/ml). Blood samples also were obtained at hourly intervals during the 24 h before and after dexamethasone administration in one woman during the follicular phase and in another woman the during the early luteal phase (progesterone levels = 1-3 ng/ml) of the ovarian cycle. DOC levels (pre-dexamethasone) fluctuated in synchrony with those of cortisol in the woman studied during the follicular phase but not in the woman studied during the early luteal phase of the cycle. In the post-dexamethasone period, plasma cortisol levels were suppressed for at least 24 h in both women whereas DOC levels were decreased only partially. We conclude that plasma DOC is derived from both adrenal secretion and from extraadrenal 21-hydroxylation of progesterone--the latter source of DOC is not affected by dexamethasone suppression of ACTH secretion.     

Adrenal responsiveness and social status in intact and ovariectomized Macaca fascicularis

Plasma cortisol (F) response to intravenous adrenocorticotropin (ACTH) infusion (following dexamethasone suppression) was examined in adult female Macaca fascicularis that had been living for 22 months in social groups consisting of four to six females and one male. A portion of these females were ovariectomized (n = 21), while the rest were reproductively intact (n = 23). The social behavior of all animals was monitored with a focal sampling procedure, and dominance ranks were determined on the basis of fight outcomes. Further, intact females were swabbed vaginally to determine onset of menstruation and were sampled for plasma progesterone (P) every three days during the luteal phase of their cycles. Among the results was that the plasma F response to ACTH infusion was greater in subordinate animals than in dominants (P < .02). Subordinates and dominants did not, however, differ in plasma F measured at baseline. It was found further that plasma F concentrations were greater in ovariectomized than in intact females at baseline and following ACTH injection (P < .01). Finally, there was an appreciable elevation in plasma F across all animals during the 15- and 30-minute post-ACTH injection measurements (P < .01). Subsequent analyses of data from intact females showed interrelationships among dominance rank, reproductive function (indicated by luteal phase plasma P concentrations), adrenal size, and adrenal response to ACTH infusion. These data indicated that subordinate females were at a reproductive disadvantage compared to dominants, a result that may have been mediated, in part, by the increased adrenal size and enhanced adrenal responsiveness of subordinate females.     

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.     

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).     

Age-related changes in blood concentration of hypothalamic-pituitary-adrenal axis hormones, their central and peripheral regulators in healthy men

We studied concentrations of cortisol, its precursors and active form in human blood and relation to the changes in concentration of central and peripheral hormonal regulators (total 36 parameters) in healthy male volunteers aged 18-72 y.o. The study demonstrated a significant decrease in blood concentrations of unutilazed cortisol precursors (pregnenolone and progesterone) with advanced age accompanied by maintenance of total and free cortisol concentrations. We found age-related decrease in ACTH level that is a known hypophysial stimulant of cortisol and cortisol precursor synthesis in adrenal glands. Cortisol and ACTH levels in study population had different correlation behavior in relation to central and peripheral regulators for hormonal axes. CONCLUSION: cortisol level remains stable with advanced age in males despite the decrease in steroidogenic activity and blood ACTH level. This may be due to the imbalance in the regulation of cortisol and ACTH production by central and peripheral regulators especially by hormones of reproductive and somatotrophic axes.     

Effects of continuous elevated cortisol concentrations during oestrus on concentrations and patterns of progesterone, oestradiol and LH in the sow

This study investigated the effect of continuous elevated cortisol concentrations during standing oestrus on time of ovulation and patterns of progesterone, oestradiol and luteinising hormone (LH) in sows. The elevation of cortisol concentrations was achieved through repeated intravenous injections of synthetic adrenocorticotropic hormone (ACTH) every 2 h for approximately 48 h, from the onset of the second standing oestrus after weaning. Treatment was terminated when ovulation was detected (monitored by transrectal ultrasonography every 4h) or when the sow had received a maximum of 24 injections. The dose of ACTH (2.5 microg/kg) was chosen to mimic the cortisol concentrations seen during mixing of unfamiliar sows. The sows (n=14) were surgically fitted with jugular vein catheters and randomly divided into a control (C group where only NaCl solution were injected) or an ACTH group. Blood samples were collected every 2 h. In parallel with the blood sampling, saliva samples for cortisol analyses were taken from eight sows before onset of treatment and from four of the sows during treatment. There was no difference in time from onset of standing oestrus to ovulation between the two groups. The interval between the peaks of oestradiol and LH to ovulation was prolonged in the ACTH group compared to the C group (p<0.05), with a tendency towards an earlier decline of oestradiol in the ACTH group. Cortisol and progesterone concentrations were significantly elevated during treatment in the ACTH group (p<0.001), with cortisol peak concentrations occurring between 40 and 80 min after each ACTH injection. Cortisol concentrations in saliva and plasma were highly correlated (p<0.001). In conclusion, elevated cortisol concentrations from the onset of standing oestrus increase progesterone concentrations and prolong the interval between oestradiol and LH peaks to ovulation, the latter possible due to an early decline in oestradiol concentrations and a change of the LH peak outline. The effect these hormonal changes have on reproductive performance need to be further investigated. Saliva samples might be a useful and non-invasive method to assess cortisol concentrations in sows.     

Maternal reproductive hormone levels after repeated ACTH application to pregnant gilts

Prenatal stress has been seen as a reason for reproductive failures in pig offspring mostly originated or mediated by changed maternal functions. In pregnant gilts, three experiments (EXP I-III) were conducted to characterize the effects of repeated ACTH on maternal cortisol concentrations (EXP I) and on the secretion of maternal reproductive hormones (LH, progesterone, estrone sulfate; EXP II + III). Exogenous ACTH was given six times every alternate day beginning either on day 49 (EXP I + II) or day 28 (EXP III) of pregnancy. As a result of treatment, elevated cortisol levels were observed for more than 6 h (EXP I). Plasma concentrations of LH were at low basal level (0.1-0.2 ng/ml), but showed a pulsatory release pattern both during first and second trimester of pregnancy. The number of LH pulses/6 h (L.S.M. +/- S.E.) of saline treated controls increased with ongoing pregnancy (1.4 +/- 0.1 versus 2.0 +/- 0.2 in EXP III and EXP II, respectively). After ACTH treatment the number of LH pulses did not differ between the two gestational stages (1.3 +/- 0.2 and 1.4 +/- 0.2 in EXP III and EXP II, respectively). However, differences ( P < 0.05) were obtained comparing the LH pulse number of ACTH and saline treated sows during the second trimester of pregnancy. Moreover, areas under the curve (AUC) of each LH pulse and of all LH values over the baseline were significantly reduced by treatment. The levels of progesterone increased (P < 0.05) for 150-170 min after each ACTH application both in EXP II and EXP III. The concentrations of 17alpha-hydroxy-progesterone revealed likewise a significant elevation after each ACTH injection. Throughout EXP III, estrone sulfate concentrations were found to decrease (from 2.8-16.9 ng/ml on day 28 to 0.02-0.04 ng/ml on day 38) but without differences between ACTH-and saline-treated gilts. Further data of EXP II and EXP III, e.g. number of piglets born alive, confirmed the absence of detrimental treatment effects. Thus, repeated ACTH administration with subsequent release of cortisol is able to influence the release pattern of maternal reproductive hormones. However, these findings demonstrate that stress-related effects are dependent on the stage of pregnancy. The detected changes may affect feto-maternal interactions and, as a result, fetal reproductive development.     

Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones

We investigated abnormalities of the hypothalamic-pituitary-gonadal axis and cortisol concentrations in women with fibromyalgia and chronic fatigue syndrome (CFS) who were in the follicular phase of their menstrual cycle, and whether their scores for depressive symptoms were related to levels of these hormones. A total of 176 subjects participated - 46 healthy volunteers, 68 patients with fibromyalgia, and 62 patients with CFS. We examined concentrations of follicle-stimulating hormone, luteinizing hormone (LH), estradiol, progesterone, prolactin, and cortisol. Depressive symptoms were assessed using the Beck Depression Inventory (BDI). Cortisol levels were significantly lower in patients with fibromyalgia or CFS than in healthy controls (P < 0.05); there were no significant differences in other hormone levels between the three groups. Fibromyalgia patients with high BDI scores had significantly lower cortisol levels than controls (P < 0.05), and so did CFS patients, regardless of their BDI scores (P < 0.05). Among patients without depressive symptoms, cortisol levels were lower in CFS than in fibromyalgia (P < 0.05). Our study suggests that in spite of low morning cortisol concentrations, the only abnormalities in hypothalamic-pituitary-gonadal axis hormones among follicular-phase women with fibromyalgia or CFS are those of LH levels in fibromyalgia patients with a low BDI score. Depression may lower cortisol and LH levels, or, alternatively, low morning cortisol may be a biological factor that contributes to depressive symptoms in fibromyalgia. These parameters therefore must be taken into account in future investigations.     

Influence of acute stress and the adrenal axis on regulation of LH and testosterone in the male rhesus monkey (Macaca mulatta)

In order to determine the mechanism by which stress may affect the secretion and function of luteinizing hormone (LH) in primates, the response of the adrenal and gonadal axes was followed in male rhesus monkeys during brief restraint in primate chairs and during various hormone treatments. To further assess the responsiveness of the gonadal axis, gonadotropin releasing hormone (GnRH) was administered during the experiments. Corticosteroid levels were elevated throughout the first restraint trial as compared to those in subsequent trials. LH was elevated in the first sample of the first trial as compared to that in the following trials. The responses of LH to GnRH were equivalent in all trials, while the testosterone response to GnRH was attenuated in the first trial. A single injection of adrenocorti-cotropin (ACTH, 40 IU), while increasing circulating corticosteroids similarly to that observed during the first restraint trial, failed to cause an acute initial release of LH. However, ACTH did lower the testosterone response to GnRH. Following 5 days of ACTH treatment (40 IU twice daily), basal LH was suppressed, and the testosterone response to GnRH was decreased. Following 5 days of cortisol injections (100 mg twice daily), basal LH and testosterone were suppressed, but again only the testosterone response to GnRH was attenuated. Acute restraint stress, acting by some mechanism other than the activation of adrenal axis, stimulates a transient release of LH. While the stress-stimulated release of corticosteroids failed to affect the LH response following GnRH administration, it did act directly on the testes to prevent the normal release of testosterone. Finally, chronic elevation of corticosteroids, produced by ACTH or cortisol administration, suppressed basal serum LH and attenuated the response of testosterone to GnRH.     

Age-related changes in the blood concentrations of the hypothalamic-pituitary-adrenal axis hormones in healthy men: Relations with other hormonal axes

The concentrations of cortisol, its precursors, and its active form in human blood, as well as its relationship to changes in the concentration of central and peripheral hormonal regulators (a total of 36 parameters), were studied in healthy male volunteers aged 18–72 years. The study demonstrated a significant decrease in the blood concentrations of unutilized cortisol precursors (pregnenolone and progesterone) with age accompanied by the maintenance of constant total and free cortisol concentrations. We found an age-related decrease in the adrenocorticotropic hormone (ACTH) level that is a well-known pituitary stimulant of cortisol and cortisol precursor synthesis in the adrenal glands. The cortisol and ACTH levels in the age interval studied exhibited different correlations with the central and peripheral regulators of the hormonal axes. The conclusion was drawn that the cortisol level remains stable with increasing age in men, despite the decrease in the steroidogenic activity and blood ACTH level. This may be due to the imbalance in the regulation of cortisol and ACTH production by the central and peripheral regulators, especially by the hormones of the reproductive and somatotrophic axes.