Daily endocrine profiles in parr and smolt Atlantic salmon

To elucidate possible mechanisms behind the endocrine control of parr–smolt transformation, the daily plasma profiles in thyroid hormones (TH; free thyroxine (FT₄), total thyroxine (TT₄), and total 3,5,3′-triiodothyronine (TT₃)), growth hormone (GH) and cortisol were studied in Atlantic salmon parr and smolts under simulated-natural winter (8 L:16D) and spring (16.5 L:7.5D) photoperiods, respectively. Overall, TT₄, TT₃ and GH levels were higher in smolts than in parr, whereas FT₄ levels fluctuated within the same range in parr and smolts. Significant diurnal changes in plasma TH were present in parr. Both FT₄ and TT₄ levels increased during the photophase and decreased during the scotophase, while TT₃ levels followed an inverse pattern. Growth hormone showed no significant changes in parr. Changes in FT₄, TT₄, GH, and cortisol, but not TT₃, levels, were observed in smolts with peak levels during both the photophase and scotophase for FT₄, TT₄ and GH. Plasma cortisol was not assayed in parr but in smolts the peaks were associated with dusk and dawn. In addition to the general increases in TH, GH and cortisol, the distinct endocrine differences in nighttime levels between parr in the winter and smolts in the spring suggest different interactions between TH, GH, cortisol and melatonin at these different time points. These spring scotophase endocrine profiles may represent synergistic hormone interactions that promote smolt development, similar to the synergistic endocrine interactions shown to accelerate anuran metamorphosis. The variations in these diurnal rhythms between parr and smolts may represent part of the endocrine mechanism for the translation of seasonal information during salmon smoltification.     

Development of young rats and rabbits exposed to a strong electric field

Body growth and circulating levels of hormones were assessed in young rats and rabbits exposed to a 50-Hz electric field of 50 kV/m. Eight-week-old male rats were exposed 8 h/day for 4 weeks and rabbits were exposed 16 h/day from the last 2 weeks of gestation to 6 weeks after birth. The body and the organ growth of exposed rats were not statistically different from those of sham-exposed controls. No important differences from controls were observed in plasma levels of corticosterone, TSH, ACTH, and T4 or in adrenal levels of epinephrine, norepinephrine, and corticosterone although T3 was slightly, but significantly, decreased. No large histological changes in the thyroid or adrenals were noted. In rabbits, organ and body weights of exposed animals were comparable to those of controls. Plasma levels of various hormones (ACTH, GH, T3, T4, corticosterone, cortisol), serum glucose, triglycerides, and cholesterol were not significantly altered. Adrenal content of cortisol was lower, however, in exposed rabbits. No histological changes of the thyroid or adrenal glands were observed.     

Influence of ACTH on serum hormone content and its anticonvulsant action towards infantile spasms

Ten patients with infantile spasms were treated with ACTH, which resulted in a suppression of thyroxine through an increase of the serum cortisol level and suppression of pituitary TSH secretion. The thyroxine level in the excellent-response group was suppressed more than that in the other groups. There was a statistically significant difference (t-test, p < 0.01) in the suppression of T₄ between the excellent-response group and the others. Although the high cortisol level was essential for the clinical effectiveness of ACTH therapy and the suppression of the thyroid hormones, the therapeutic correlation with the elevated cortisol level might be weak as compared to that with the suppression of T₄. These findings suggest the possibility that the efficacy of ACTH therapy in infantile spasms may depend in part on the suppression of the thyroid hormone.     

Response to confinement in sea bass (Dicentrarchus labrax) is characterised by an increased biosynthetic capacity of interrenal tissue with no effect on ACTH sensitivity

Two experiments were carried out to investigate the influence of confinement stress on plasma cortisol levels and on the sensitivity of the interrenal cells to adrenocorticotropic hormone (ACTH) stimulation in sea bass Dicentrarchus labrax. Confining sea bass at 70 kg m(-3) for 24 h resulted in elevated plasma cortisol levels at all times (0.1, 1, 4 and 24 h) and corresponded to a reduced cortisol content in head-kidney homogenates after 0.1 and 1 h of confinement. An increased activity of the interrenal cells was also indicated by the enlarged nuclear diameters measured after 1 and 4 h of confinement. In vitro superfusion experiments showed that 4 h of confinement resulted in an increased basal unstimulated release of cortisol from head-kidney tissues compared with that in unstressed control fish. Although the stimulation factor (cortisol release as percent increase above basal) of the stressed fish was significantly lower than in controls, no difference in the maximal stimulated release (in absolute amounts) was evident between stressed and control fish. Care must be taken when interpreting superfusion data, as to whether the stressor actually leads to a reduction in interrenal sensitivity, or is due to an alteration in the basal release of cortisol.     

Interference of o,p'DDD with interrenal function and cortisol metabolism in Sarotherodon aureus (Steindachner)

The purpose of this study was to investigate possible effects of organochlorine residues on cortisol balance in a freshwater fish. The combined stress of netting, handling and blood sampling in Sarotherodon aureus normally results in a twofold increase of circulating cortisol, within 30–60 min. Fish treated with o,p'DDD (50 mg kg⁻¹) had higher resting level of cortisol than before treatment (155.8±12.7 v. 86.9± 11.2 ngmh⁻¹; n=16). No further increase in cortisol level occurred in these fish after exposure to stress; this inability to respond was maintained for more than 120 days. A recovery of the response to ACTH by superfused interrenal tissue from the treated fish was observed 255 days after treatment. Successive blood sampling of o,p'DDD-treated fish, injected intracardially with labelled cortisol, have shown that the half-life of the steroid in the circulation is prolonged by 370% compared with controls. The hepatic metabolism of cortisol was studied by incubating liver slices with the labelled hormone. Hepatic tissue from o,p'DDD-treated fish metabolized cortisol slower than livers from controls. The high resting level of cortisol in plasma of fish treated with o,p'DDD may be attributed to the retarded metabolism of the steroid by the liver. The lack of augmented cortisol levels in response to stress is attributed to the interference of the organochlorine with the response of the interrenal tissue to the stress-induced surge of endogenous ACTH.     

The effect of marathon racing on serum concentrations of selected hormones in health and disabled individuals

Serum concentrations of the selected hormones were assayed in students who did not train long-distance races and in trained disabled individuals who passed the distance on a wheel chairs. Assays were carried out both prior to and after Marathon race. An exercise significantly increased serum concentrations of the following hormones in both groups: cortisol, ACTH, aldosteron, and plasma renin activity. An increase in total thyroxine, free thyroxine and decrease in LH were noted in disabled individuals. Increased concentrations of ACTH, free and total thyroxine, decreased concentrations of cortisol, LH, plasma renin activity, and aldosteron were found in disabled individuals who passed the distance of Marathon race on the wheel chairs comparing with those seen in the students.     

Alterations in Hypothalamus-Pituitary-Adrenal/Thyroid Axes and Gonadotropin-Releasing Hormone in the Patients with Primary Insomnia: A Clinical Research

The hypothalamus-pituitary-target gland axis is thought to be linked with insomnia, yet there has been a lack of further systematic studies to prove this. This study included 30 patients with primary insomnia (PI), 30 patients with depression-comorbid insomnia (DCI), and 30 healthy controls for exploring the alterations in the hypothalamus-pituitary-adrenal/thyroid axes’ hormones and gonadotropin-releasing hormone (GnRH). The Pittsburgh Sleep Quality Index was used to evaluate sleep quality in all subjects. The serum concentrations of corticotrophin-releasing hormone (CRH), thyrotrophin-releasing hormone (TRH), GnRH, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), cortisol, total triiodothyronine (TT3), and total thyroxine (TT4) in the morning (between 0730 h and 0800 h) were detected. Compared to the controls, all hormonal levels were elevated in the insomniacs, except ACTH and TSH in the PI group. Compared to the DCI patients, the PI patients had higher levels of CRH, cortisol, TT3, and TT4 but lower levels of TRH, GnRH, and ACTH. Spearman’s correlation analysis indicated that CRH, TRH, GnRH, TSH, cortisol, TT4, and TT3 were positively correlated with the severity of insomnia. The linear regression analysis showed that only CRH, GnRH, cortisol, and TT3 were affected by the PSQI scores among all subjects, and only CRH was included in the regression model by the “stepwise” method in the insomnia patients. Our results indicated that PI patients may have over-activity of the hypothalamus-pituitary-adrenal/thyroid axes and an elevated level of GnRH in the morning.     

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.     

The hormonal content of the hypophyseal-adrenocortical system in the blood of the suslik Citellus undulatus at different seasons of the year

Radioimmune assay has been made of the content of ACTH and cortisol in the peripheral blood of the ground squirrel Citellus undulatus parryi at various seasons and during a short hibernation period. Within annual cycle, negative relationship was observed between ACTH and cortisol levels. Cortisol content decreases from Autumn to Winter; the content of ACTH in the blood plasma, measured during periodic arousals, increases progressively during hibernation. Concentration of both hormones significantly decreases in sleeping animals, increasing during arousals. At the beginning of hibernation period, cortisol content gradually decreases. During self-warming of arousing animals, cortisol content remains low. The decreased production of cortisol in hibernating animals is presumably associated with the increase in the threshold of sensitivity of the adrenal receptors to stimulating effect of ACTH. The role of glucocorticoids and ACTH in the metabolism of hibernating animals is discussed.     

Changes in intestinal fluid transport associated with smoltification and seawater adaptation in coho salmon, Oncorhynchus kisutch (Walbaum)

The intestinal role in osmoregulatory preadaptation of freshwater-adapted (FW) yearling coho salmon during smoltification was examined. Measurements of intestinal net fluid absorption (J_V) using an in vitro sac preparation showed that J_V of FW parr was significantly less than that of either FW or seawater-adapted (SW) smolts. From two to four weeks following the springtime thyroxin surge, J_V increases in FW coho to a level comparable with that observed for SW smolts. J_V remained elevated in FW smolts throughout most of the summer and then decreased in the autumn. Two months after the thyroxin peak, intestinal wet weight per unit serosal surface area increases. Coho stunts resulting from premature transfer into sea water had significantly higher J_V than that seen in SW smolts. The elevated J_V of stunts is only partially explicable on the basis of differences in body weight between stunts and smolts.
Our observations indicate that an increase in intestinal fluid absorption is a preadaptive change associated with smoltification occurring in concert with alterations in renal and branchial osmoregulatory mechanisms. The timing of the increase in J_V suggests a phase relationship to the thyroxin surge. This temporal relationship may help to explain the efficacy of using changes in plasma thyroxin levels to predict hatchery-fish release dates that may optimize eventual seawater survival.     

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 exogenous thyroxine or prior exposure to raised water-flow on the downstream movement of hatchery-reared Atlantic salmon smolts

Administration of thyroxine to hatchery-reared Atlantic salmon smolts raised blood serum thyroxine levels 24 h later to exceed those in controls. Treatment also slowed downstream movement when smolts were released into a stream above a fish trap. The descent of smolts released immediately after being challenged with high-water flows for several hours was also slowed, and proportionately fewer challenged fish than controls were captured at the fish trap. These findings were consistent in each of two years. Only in one year, however, could flow-challenge be shown to raise endogenous thyroxine levels in blood serum. It is concluded that exogenous thyroxine treatment and flow-challenge before release have qualitatively similar effects on downstream movement but that this similarity is possibly not a consequence of the common effect of increased serum thyroxine raised either exogenously or from the thyroid system itself.     

Reciprocal interaction between seasonal testis and thyroid activity in Zembra Island wild rabbits (Oryctolagus cuniculus): effects of castration, thyroidectomy, temperature, and photoperiod

The reproductive cycle of wild rabbits (Oryctolagus cuniculus) living in Zembra Island (North Tunisia) is dependent on an external factor, the photoperiod: the gonads are inhibited by long days and stimulated by short days or melatonin implants. Here we studied the role of an internal factor, thyroid hormones and the possible thyroid-gonadal interrelationships, in animals captured on Zembra Island and maintained in natural conditions of photoperiod and temperature. We determined the seasonal profile of the thyroid and testis cycles and investigated the effects of castration and thyroidectomy on the seasonal testosterone and thyroxine cycles. Plasma thyroxine and testosterone levels followed similar, parallel seasonal patterns, with a peak in autumn (October) and low values from January to August. In thyroidectomized animals, plasma testosterone levels, although significantly higher than those in controls (P < 0.001), remained low throughout the 13 mo of the experiment, and no testicular reactivation was observed in the fall. In castrated animals, despite the increase in thyroxine concentration in the 3 mo following castration (P < 0.01), plasma thyroxine levels remained low during the 2 yr of the study. We then investigated the combined effects of long days (16L:8D) and moderately high temperature (25 degrees C) on these two endocrine axes. In constant gonado-inhibiting conditions (16L:8D), whether the temperature was kept constantly high or allowed to fluctuate naturally, no reactivation of the thyroid and testicular axes was observed in the fall. In control animals, the peaks of testosterone and thyroxine concentrations observed in September were larger (P < 0.001) than those in animals subjected to the same natural photoperiod conditions but with constantly high temperature. The lower level of autumnal testis stimulation (P < 0.001) in animals maintained in conditions of constant high temperature (25 degrees C) may be attributed to the low thyroxine levels induced by high temperature. These results clearly confirm that the thyroid and testicular cycles display similar seasonal variations and show that the thyroid and gonadal axes are strictly interdependent. This study provides the first demonstration, for a given species, that the seasonal reactivation of gonad activity is controlled by the thyroid, and thyroid activity is controlled by the gonads.     

Hormonal responses to analgesic nitrous oxide in man

Analgesic concentrations of nitrous oxide were administered to 6 healthy male subjects, and blood samples were assayed for prolactin, ACTH, follicle stimulating hormone, luteinising hormone, growth hormone, cortisol and thyroid hormones. Analgesic nitrous oxide (mean concentration = 48.8%) produced statistically significant elevation of prolactin and depression of cortisol whilst not producing statistically significant changes in the other hormones assayed. The increase in prolactin and decrease in cortisol levels are similar to the hormonal changes associated with administration of opioids in man. We have also confirmed the findings of other workers that cortisol levels may not always be correlated with ACTH levels.     

Effects of glucocorticoids on plasma levels of thyroid hormones (T4 and T3) and testicular activity in catfish, Clarias gariepinus during different phases of annual breeding cycle

Effects of short-term administration of corticosterone and cortisol on plasma levels of thyroid hormones, gonado-somatic index and testicular histology have been reported in catfish, Clarias gariepinus during different phases of its breeding cycle. Corticosterone administration had no significant effect on plasma levels of T4, T3 and T3/T4 ratio, irrespective of doses and phases of breeding cycle. However, 5 microg dose of cortisol significantly increased plasma levels of T3 and the T3/T4 ratio during quiescent and regressive phases, while it significantly decreased plasma levels of T4 during progressive phase. During breeding phase, 2 microg and 5 microg doses of cortisol significantly decreased plasma levels of T4 and T3, respectively, while 5 microg dose of cortisol alone reduced T3/T4 ratio. Irrespective of phases of annual breeding cycle and doses, short-term administration of corticosterone and cortisol had no significant effect either on GSI or testicular histology. These findings suggest that corticosterone is ineffective in stimulating plasma levels of thyroid hormones, while cortisol, depending on dose and phase/season, may differentially increase, decrease or have no effect on plasma levels of thyroid hormones in C. gariepinus.     

Hormonal Interaction in Amphibian Metamorphosis

SYNOPSIS. The climactic stages of amphibian metamorphosis constitutea period characterized by radical morphological changes thatare driven primarily by the thyroidal hormones. Radioimmunoassaysshow that levels of thyroid hormones (TH) rise to a peak duringmetamorphic climax. Accompanying peaks are reported for ACTH,adrenal corticoids (AC), insulin (I) and prolacdn (PRL). ACenhance the metamorphic action of TH by increasing their bindingto nuclei of target cells. TH, in turn, act to raise levelsof AC by stimulating the differentiation of the median eminencethus facilitating the flow of a CRF from the hypothalamus tothe adenohypophysis, by synergizing with ACTH and bystimulationof the interrenals through some other route. During the metamorphicperiod, at least as far as climax, PRL antagonizes TH, perhapsat the thyroidal level and certainly at the level of targetcells. PRL may antagonize by inhibiting induction of hydrolyticenzymes by TH, by alteration of hydromineral responses or byaltering levels of binding of TH to receptors. The antagonisticaction of PRL is mimicked by cAMP. A surge of PRL that is releasedinto the plasma during metamorphic climax seemingly producesno antagonistic effect on thyroidal actions.     

Interaction of thyroid hormones and cortisol on binding proteins of cytosol and nuclear extract of human leukocytes

Competitive properties of thyroid hormone analogues and cortisol for the binding of triiodothyronine and thyroxine, expressed as apparent inhibition constants (Ki), have been measured in nuclear extract and cytosol proteins of human leukocytes by means of electrophoresis in polyacrylamide gradient gel and charcoal-dextran assay. In the cytosol not only thyroid hormones but also cortisol competed for the binding of triiodothyronine and thyroxine as tested by charcoal-dextran assay. By means of electrophoresis two protein fractions binding thyroid hormones were found: protein fraction designed A (m. w. 100,000) and protein fraction B (m. w. 83,000). In protein fraction A the inhibition constant Ki for thyroid hormones are lower than in protein fraction B. In the protein fraction B not only thyroid hormones but also cortisol competed for the binding of triiodothyronine and thyroxine. In the nuclear extract the thyroid hormones were bound in one protein fraction C (m. w. 58,000) only. In this protein fraction only thyroid hormones, but not cortisol, are competitors for the binding of triiodothyronine and thyroxine and in the following descending order: triiodothyronine, thyroxine, tetraiodothyroacetic acid, thyroxamine and D-thyroxine. The competition of cortisol for the binding of thyroid hormones in cytosol protein fraction B in connection with some serum TBG changes in patients after prednisone administration is discussed.     

Responsiveness of the interrenal tissue of Jundiá (Rhamdia quelen) to an in vivo ACTH test following acute exposure to sublethal concentrations of agrichemicals

As in many aquatic environments, pollution is a widespread problem in Southern Brazil. In our previous work, we demonstrated that sublethal contamination with some agrichemicals impairs the capacity of fishes to elevate cortisol levels in response to an additional acute stressor. In earlier experiments, the experimental design did not allow us to conclude where this effect occurs. In the present work, we used the adrenocorticotropic hormone (ACTH) challenge test to help us identify if the impairment occur in the interrenal tissue. For this purpose, five experiments were conducted, each with one specific agrichemical (methyl-parathion, atrazine+simazine, atrazine, tebuconazole, and glyphosate) in sublethal concentrations of 16.6% of the LC(50-96h), as previously determined. Fish were subjected to the ACTH challenge test protocol as follows: group 1, were non-injected and maintained as the specific control group; group 2 received an injection of the vehicle alone (the saline group); and group 3 receive an injection of ACTH. One hour later, blood samples were taken from the caudal plexus, using sterile syringes. In all specific control groups, the injection of ACTH induced a strong rise in plasma cortisol, compared with the fish injected only with the vehicle and the non-injected group. Fish exposed to methyl-parathion and tebuconazole did not elevate cortisol in response to the ACTH injection, with values significantly lower than the control fish. Fish exposed to sublethal concentrations of atrazine+simazine, atrazine, and glyphosate showed a rise in plasma cortisol very similar to the control fish. We conclude that the ACTH challenge test revealed that R. quelen exposed to sublethal concentrations of tebuconazole and methyl-parathion had a reduced ability to elevate plasma cortisol in response to an intraperitoneal (i.p.) injection of exogenous ACTH, indicating that the interrenal tissue is the site of the impairment within the HPI axis. These ACTH challenge tests also revealed that the impairment of the cortisol response verified in fish exposed to atrazine+simazine and glyphosate, as shown in our previous work, seems to be related to steps of cortisol secretion in higher levels within the HPI axis.     

PCB disruption of the hypothalamus-pituitary-interrenal axis involves brain glucocorticoid receptor downregulation in anadromous Arctic charr

We examined whether brain glucocorticoid receptor (GR) modulation by polychlorinated biphenyls (PCBs) was involved in the abnormal cortisol response to stress seen in anadromous Arctic charr (Salvelinus alpinus). Fish treated with Aroclor 1254 (0, 1, 10, and 100 mg/kg body mass) were maintained for 5 mo without feeding in the winter to mimic their seasonal fasting cycle, whereas a fed group with 0 and 100 mg/kg Aroclor was maintained for comparison. Fasting elevated plasma cortisol levels and brain GR content but depressed heat shock protein 90 (hsp90) and interrenal cortisol production capacity. Exposure of fasted fish to Aroclor 1254 resulted in a dose-dependent increase in brain total PCB content. This accumulation in fish with high PCB dose was threefold higher in fasted fish compared with fed fish. PCBs depressed plasma cortisol levels but did not affect in vitro interrenal cortisol production capacity in fasted charr. At high PCB dose, the brain GR content was significantly lower in the fasted fish and this corresponded with a lower brain hsp70 and hsp90 content. The elevation of plasma cortisol levels and upregulation of brain GR content may be an important adaptation to extended fasting in anadromous Arctic charr, and this response was disrupted by PCBs. Taken together, the hypothalamus-pituitary-interrenal axis is a target for PCB impact during winter emaciation in anadromous Arctic charr.     

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.