Effect of electroacupuncture at Zusanli (ST36) and Sanyinjiao (SP6) acupoints on adrenocortical function in etomidate anesthesia patients.

BACKGROUND: We aimed to investigate the effect of electroacupuncture at Zusanli (ST36) and Sanyinjiao (SP6) on adrenocortical function in patients with etomidate anesthesia. MATERIAL AND METHODS: We randomly divided 80 patients who underwent elective surgery into 4 groups: group etomidate (ETO), group etomidate + electroacupuncture (ETO+EA), group etomidate + sham acupuncture (ETO+SEA), and group propofol (PRO). The patients in group ETO, ETO+EA, and ETO+SEA were induced with etomidate and sufentanil and maintained with intravenous infusion of etomidate and remifentanil. Group PRO was induced with propofol and sufentanil and maintained with propofol and remifentanil. Group ETO+EA received electro-acupuncture stimulation at Zusanli and Sanyinjiao throughout the operation, while group ETO+SEA received electro-acupuncture stimulation at non-acupoints. We recorded the values of MAP, HR, BIS, CVP, cortisol, ACTH, epinephrine, norepinephrine, and arterial blood gas during the perioperative period. RESULTS: Cortisol concentrations were significantly higher at all times except T0 in group ETO+EA compared with group ETO. The ACTH concentrations were lower in group ETO+EA than that in group ETO at point T3. CONCLUSIONS: Electroacupuncture at ST 36 and SP 6 can mitigate the adrenal cortical inhibition induced by etomidate and can reduce the secretion of catecholamines during surgery.

The relationship between adrenocortical function and Hsp70 expression in socially isolated Japanese quail.

Physiological responses to social isolation stress were compared in 56-day-old male Japanese quail. Birds were fed pretreated diets for 3 days as follows: (i) Basal diet (control); (ii) Basal diet+1500 mg/kg metyrapone (BM); (iii) Basal diet+30 mg/kg corticosterone (BCO); (iv) Basal diet+250 mg/kg ascorbic acid (BC); (v) Basal diet+250 mg/kg α-tocopherol (BE); (vi) Basal diet+250 mg/kg ascorbic acid and 250 mg/kg α-tocopherol (BCE). The birds were subsequently socially isolated in individual opaque brown paper box for 2 hours. Plasma corticosterone (CORT) concentration and heart and brain heat shock protein 70 (Hsp 70) expressions were determined before stress and immediately after stress. Two hours of isolation stress elevated CORT concentration significantly in the control and BE birds but not in the BC, BCE and BM birds. There was a significant reduction in CORT concentration after isolation stress in the BCO group. Isolation stress increased Hsp 70 expression in the brain and heart of control and BM birds. However, brain and heart Hsp 70 expressions were not significantly altered in the isolated BC, BCE and BE birds. Although, the CORT concentration of BM birds was not affected by isolation stress, Hsp70 expression in both brain and heart were significantly increased. Moreover, exogenous corticosterone supplementation did not result in elevation of Hsp 70 expression. It can be concluded that, although Hsp 70 induction had not been directly affected by CORT concentration, it may be modulated by the HPA axis function via activation of ACTH.

The function of the adrenocortical axis in permanent middle cerebral artery occlusion: effect of glucocorticoids on the neurological outcome.

We characterized the effect of acute ischemic stroke on the activation of the hypothalamic-pituitary-adrenal (HPA) axis and evaluated the role of glucocorticoids (GC) in the clinical outcome following ischemic stroke. Male spontaneous hypertensive rats underwent permanent middle cerebral artery occlusion (PMCAO) and developed a cortical infarct. At 4h post-PMCAO or sham operation, serum levels of ACTH and corticosterone (CS) were elevated 5 and 4 fold respectively as compared to controls and then returned to basal levels at 24h post surgery. In these experimental groups we found also a significant depletion of median eminence (ME)-CRH(41). In adrenalectomized (Adx) rats that underwent PMCAO the degree of motor disability and infarct volume was similar to that of intact rats. Administration of dexamethasone (Dex) to Adx-PMCAO rats significantly improved the motor disability and decreased the infarct volume. However, in sham-Adx with PMCAO, Dex had no effect on these two parameters. In rats with PMCAO or sham-PMCAO, brain production of PGE(2) was significantly increased. This effect was further enhanced in Adx-PMCAO rats and significantly inhibited by Dex. In conclusion, activation of the HPA axis following PMCAO is due to stress induced by surgery. This activation is mediated by hypothalamic CRH(41). Absence of endogenous GC or administration of Dex in naïve rats does not alter motor and pathological parameters in the acute stage following PMCAO. In contrast, administration of Dex significantly improved the outcome following cerebral ischemia in Adx rats which may be due to increased glucocorticoid receptors. Brain production of PGE(2) does not play an important role in the pathophysiology of the acute phase of cerebral ischemia.

Molecular regulation of the hypothalamic-pituitary-adrenal axis in adult male guinea pigs after prenatal stress at different stages of gestation.

Studies in humans and animals have demonstrated that maternal stress during fetal development can lead to altered hypothalamic-pituitary-adrenal (HPA) axis function and behaviour postnatally. We have previously shown adult male guinea pigs that were born to mothers exposed to a stressor during the phase of rapid fetal brain growth (gestational days (GD) 50, 51 and 52; prenatal stress (PS)50) exhibit significantly increased basal plasma cortisol levels. In contrast, male guinea pig offspring whose mothers were exposed to stress later in gestation (GD60, 61 and 62; PS60) exhibited a significantly higher plasma cortisol response to activation of the HPA axis. In the present study, we hypothesized that the endocrine changes in HPA axis function observed in male guinea pig offspring would be reflected by altered molecular regulation of the HPA axis. Corticosteroid receptors in the hippocampus, hypothalamus and pituitary were measured, as well as corticotropin-releasing hormone (CRH), pro-opiomelanocortin (POMC) and adrenal enzymes in the paraventricular nucleus, pituitary and adrenal cortex, respectively, by in situ hybridization and Western blot. PS50 male offspring exhibited a significant reduction in glucocorticoid receptor (GR) mRNA (P <0.01) in the CA3 region of the hippocampus and significantly increased POMC mRNA (P <0.05) in the pituitary, consistent with the increase in basal HPA axis activity observed. In line with elevated activity of the HPA axis, both PS50 and PS60 male offspring exhibited significantly higher steroidogenic factor (SF)-1 (P <0.001) and melanocortin 2 receptor (MC2-R) mRNA (P <0.001) in the adrenal cortex. This study demonstrates that short periods of prenatal stress during critical windows of neuroendocrine development affect the expression of key regulators of HPA axis activity leading to the changes in endocrine function observed in prenatally stressed male offspring. Further, these changes are dependent on the timing of the maternal stressor, a pattern that is emerging in human studies.

Estrogens contribute to a sex difference in plasma potassium concentration: a mechanism for regulation of adrenal angiotensin receptors.

BACKGROUND: The adrenal mineralocorticoid aldosterone promotes sodium (Na(+)) reabsorption and potassium (K(+)) loss from the kidney. Female sex steroids such as estrogen and progesterone are known modulators of the renin-angiotensin-aldosterone system. OBJECTIVE: We conducted studies to determine if there is a sex difference in plasma Na(+) concentration ([Na(+)]) and plasma K(+) concentration ([K(+)]), and if interactions between female sex steroids and aldosterone contribute to a sex difference in these electrolytes. METHODS: Plasma [Na(+)] and [K(-)] were determined in weight-matched male and female Sprague-Dawley rats using an ion-selective electrode system. To assess the sensitivity of males and females to aldosterone, the mineralocorticoid was infused chronically by osmotic minipump. The role of female sex steroids in the regulation of plasma electrolyte concentrations was determined in bilaterally ovariectomized (OVX) female rats treated daily with SC injections of progesterone, 17beta-estradiol (E(2)), or selective estrogen receptor (ER) modulators. The role of plasma [K(+)] in the regulation of adrenal angiotensin II type 1 receptor (AT(1)R) expression was determined by manipulating plasma [K(+)] by varying dietary K(-). Adrenal AT(1)R expression was assessed using a radioligand binding assay. RESULTS: Plasma [Na(-)] was not different between male and female rats, but plasma [K(-)] was reduced in females compared with males (P = 0.003). In aldosterone-infused female rats, plasma [Na(+)] was increased and plasma [K(+)] was reduced further than in male rats infused with aldosterone (both, P = 0.001). In OVX female rats, progesterone reduced plasma [Na(+)] (P = 0.04) but had no effect on plasma [K(+)]. In contrast, E(2) increased plasma [Na(+)] (P = 0.01) and reduced plasma [K(+)] (P = 0.001). Dietary K supplementation in E(2)-treated rats returned plasma [K(+)] and adrenal AT(1)R binding to levels observed in control rats. Both an ERa and ERP agonist decreased plasma [K(+)] and decreased adrenal AT(1)R binding (both, P < 0.01). CONCLUSIONS: In these studies, plasma [K(+)] was reduced in female Sprague-Dawley rats compared with males. The effects of aldosterone on plasma electrolytes were enhanced in females compared with males. E(2) treatment reduced plasma [K(+)] and adrenal AT(1)R binding in OVX rats, and the decrease in plasma [K(+)] contributed to the decrease in adrenal AT(1)R binding. Both ERalpha and ERbeta contributed to the estrogen-induced decrease in plasma [K(+)] and adrenal AT(1)R binding.

Salivary cortisol as an indicator of adrenocortical function in healthy infants, using massage therapy.

CONTEXT AND OBJECTIVE: The evaluation of adrenocortical function with the use of therapeutic massage has been little studied in Brazil. The purpose of this study was to evaluate the salivary cortisol levels before and after Shantala massage therapy on healthy infants. DESIGN AND SETTING: Prospective case series, in a public nursery, in São Paulo. METHODS: Saliva was obtained from 11 infants at the times of 8:00-9:00 a.m. and 4:00-5:00 p.m. in a nursery and 9:00-10:00 p.m. at home. They received a 15-minute therapeutic massage on two consecutive days, and saliva was collected before and after the massage. The procedure was repeated after a one-week interval. Cortisol values (intra-assay < 5%; inter-assay < 10%) at different times of the day were compared by ANOVA. RESULTS: The mean cortisol values (nmol/l +/- SD) on the first day were: morning (M) = 14.1 +/- 5.7, afternoon (A) = 8.3 +/- 2.7, night (N) = 3.3 +/- 1.1; after two consecutive days of therapeutic massage: M = 22.3 +/- 13.5, A = 13.4 +/- 6.0, N = 5.8 +/- 3.5; after a one-week interval: M = 15.8 +/- 7.7, A = 14.3 +/- 7.7, N = 3.4 +/- 2.0. CONCLUSION: There was a modification in the salivary cortisol values following massage, thus reflecting possible adaptation of the hypothalamic-pituitary-adrenal axis.

Modeling robust oscillatory behavior of the hypothalamic-pituitary-adrenal axis.

A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis of the human endocrine system is proposed. This new model provides an improvement over previous models by introducing two nonlinear factors with physiological relevance: 1) a limit to gland size; 2) rejection of negative hormone concentrations. The result is that the new model is by far the most robust; e.g., it can tolerate at least -50% and +100% perturbations to any of its parameters. This high degree of robustness allows one, for the first time, to model features of the system such as circadian rhythm and response to hormone injections. In addition, relative to its closest predecessor, the model is simpler; it contains only about half of the parameters, and yet achieves more functions. The new model provides opportunities for teaching endocrinology within a biological or medical school context; it may also have applications in modeling and studying HPA axis disorders, for example, related to gland size dynamics, abnormal hormone levels, or stress influences.

Effects of milk production capacity and metabolic status on HPA function in early postpartum dairy cows.

Increasing milk yields in modern dairy cows cause concern that high yield may impair the cows' health and welfare, for example, via negative effects on metabolic status and hypothalamo-pituitary-adrenocortical (HPA) function. This study aims to investigate whether a high level of milk production, and the associated metabolic status, affects HPA function in dairy cows and changes their adaptive capacity. Additionally, it aims to establish whether possible effects of milk production level only show under challenging conditions. Holstein-Friesian cows, which produced on average 11,443 and 7727 kg of fat and protein-corrected milk (FPCM)/305 d in their previous lactation, were compared. During the dry period, the cows were fed to requirements or overfed. High milk yield and the concomitant large energy deficit were associated with 1) increased pituitary (re)activity, i.e., increased ACTH baseline concentrations and higher ACTH concentrations after corticotropin-releasing hormone (CRH) administration, and 2) decreased adrenocortical reactivity, i.e., lower cortisol responses after ACTH administration. Although significant, the effects of milk production level on HPA function were relatively small. Animals showed seemingly normal hormonal responses to CRH and ACTH administration. Also, cortisol baseline concentrations were unaffected. It seems, therefore, unlikely that the adaptive capacity of the high-producing cows was significantly impaired compared with their low-producing herdmates.

Prenatal glucocorticoid exposure alters hypothalamic-pituitary-adrenal function and blood pressure in mature male guinea pigs.

Pregnant guinea pigs were treated with dexamethasone (1 mg kg(-1)) or vehicle on days 40-41, 50-51 and 60-61 of gestation, after which animals delivered normally. Adult male offspring were catheterized at 145 days of age and subjected to tests of hypothalamic-pituitary-adrenal (HPA) axis function in basal and activated states. Animals exposed to dexamethasone in utero (mat-dex) exhibited increased hippocampus-to-brain weight ratio, increased adrenal-to-body weight ratio and increased mean arterial pressure. There were no effects on gestation length, birth weight and postnatal growth. There were no overall differences in diurnal plasma adrenocorticotropic hormone (ACTH) and cortisol profiles, though there were subtle differences during the subjective afternoon between control and mat-dex offspring. A significant decrease in initial ACTH suppression was observed following dexamethasone injection in mat-dex offspring compared to control offspring. Molecular analysis revealed significantly increased MR mRNA expression in the limbic system and particularly in the dentate gyrus in mat-dex offspring. In the anterior pituitary, both pro-opiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA levels were significantly elevated in mat-dex offspring. In conclusion, (1) repeated prenatal treatment with synthetic glucocorticoid (sGC) permanently programmes organ growth, blood pressure and HPA regulation in mature male offspring and these changes involve modification of corticosteroid receptor expression in the brain and pituitary; (2) the effects of prenatal sGC exposure on HPA function appear to change as a function of age, indicating the importance of investigating HPA and cardiovascular outcome at multiple time points throughout life.

Ontogeny of the hypothalamo-pituitary-adrenocortical axis in the chicken embryo: a review.

The embryo of the domestic fowl (Gallus domesticus) tenders one distinctive advantage over general mammalian models for investigating the development of the hypothalamo-pituitary-adrenocortical (HPA) axis. This is the relative simplicity with which the embryonic endocrine environment can be influenced without confounding maternal influences. The ease of direct manipulation of the embryonic endocrine system has facilitated analysis of the development and function of the HPA axis in the chick embryo. As the chick embryo develops, functional activation of the adrenal gland is regulated at three different levels: the adrenal gland itself, the anterior pituitary, and the hypothalamus. The adrenal gland appears capable of independent secretion of glucocorticoids from day 8 until shortly after day 14 of embryonic development, at which point the pituitary influences adrenocortical activity. Around the same age, the hypothalamic level of control also begins. The information covered in this review will describe the major steps in the development of the HPA axis in the chicken embryo and show that the chicken has an emblematic HPA neuroendocrine axis.

Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.

Repeated citalopram treatment but not stress exposure attenuates hypothalamic-pituitary-adrenocortical axis response to acute citalopram injection.

Many experimental, clinical and epidemiological studies have shown a direct connection between exposure to stress or adverse life events and disease, but little is known about the effect of stress on the action of drugs. The aim of this study was to test the hypothesis that previous exposure to stress changes the action of the antidepressant drug citalopram (10 mg/kg, i.p.) on hypothalamic-pituitary-adrenocortical (HPA) axis function, gene expression of selected neuropeptides and serotonin reuptake. Three different stress models were used, which included immobilization, restraint and unpredictable stress stimuli. Samples of plasma for hormone measurement were taken from conscious cannulated animals. Changes in corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) gene expression in the paraventricular nucleus of the hypothalamus and the anterior pituitary, respectively, and the ability of citalopram to inhibit serotonin reuptake were investigated. The exposure to three different stress models did not influence citalopram action on individual parameters of HPA axis and on serotonin reuptake. On the other hand, repeated administration of the drug led to significant attenuation of ACTH and CRH mRNA responses. The present results allow to suggest that the stressors used did not influence serotonergic neurotransmission to the extent that would modify HPA axis response to citalopram challenge. Activation of HPA axis by acute citalopram treatment was found to be accompanied by increased CRH gene expression in the hypothalamus. Repeated administration of the drug led to the development of tolerance to activation of central and peripheral components of HPA axis, but not to serotonin reuptake inhibition.

Modulation of steroidogenesis by selenium in a novel adrenal cell line developed using targeted tumorigenesis.

UNLABELLED: Glutathione peroxidase (GPx-1) is a selenoenzyme that metabolizes H(2)O(2), a source of potentially toxic free radicals. Steroidogenesis is markedly inhibited by H(2)O(2) in vitro. OBJECTIVE: to study the effects of selenium deficiency on GPx activity and adrenal steroidogenesis in a novel adrenal cell line developed using targeted tumorigenesis. METHODS: AN4Rppc7 cells were grown for 7 days in serum-free medium. 8-Br-cAMP-stimulated concentrations of steroid hormones were measured by RIA. StAR (Steroid Acute Reactive Protein) mRNA was measured by Northern blot. RESULTS: selenium deficiency caused a 99% There was a 51%, progesterone, corticosterone and aldosterone production, respectively (p<0.05 by ANOVA). StAR mRNA was not affected by selenium. CONCLUSIONS: selenium deficiency causes a marked decrease in GPx activity. Decreased steroid hormone production occurs for selenium concentrations equal or lower than 5 nM. The absence of changes in StAR mRNA content suggests that selenium deficiency does not affect cholesterol access to the mitochondria.

Ouabain, a new steroid hormone of adrenal gland and hypothalamus.

Ouabain has been isolated and identified as a constituent of human blood, bovine adrenal glands and hypothalamus. This water soluble inhibitor of the sodium pump (Na+/K+-ATPase) circulates in elevated concentrations in blood plasma of 50% of Caucasians with elevated blood pressure. It is released from adrenal cortical cells in tissue culture by angiotensin II. A ouabain antagonist, PST2238, lowers blood pressure in hypertensive rats. Hence, ouabain is most probably a new steroid hormone formed in adrenal glands and hypothalamus. Consistent therewith is the demonstration of a specific binding globulin for cardiac glycosides in blood plasma.

Selective activation of the hypothalamic vasopressinergic system in mice deficient for the corticotropin-releasing hormone receptor 1 is dependent on glucocorticoids.

Deficiency of CRH receptor 1 (CRHR1) severely impairs the stress response of the hypothalamic-pituitary-adrenocortical (HPA) system and reduces anxiety-related behavior in mice. Intriguingly, in mice deficient for the CRHR1 (Crhr1-/-), basal plasma levels of ACTH are normal, suggesting the presence of compensatory mechanisms for pituitary ACTH secretion. We therefore studied the impact of the hypothalamic neuropeptides arginine vasopressin (AVP) and oxytocin (OXT) on HPA system regulation in homozygous and heterozygous Crhr1 mutants under basal and different stress conditions. Basal plasma AVP concentrations were significantly elevated in Crhr1-/- mice. AVP messenger RNA expression was increased in the paraventricular nucleus of Crhr1-/- mutants together with a marked increase in AVP-like immunoreactivity in the median eminence. Administration of an AVP V1-receptor antagonist significantly decreased basal plasma ACTH levels in mutant mice. After continuous treatment with corticosterone, plasma AVP levels in homozygous Crhr1-/- mice were indistinguishable from those in wild-type littermates, thus providing evidence that glucocorticoid deficiency is the major driving force behind compensatory activation of the vasopressinergic system in Crhr1-/- mice. Neither plasma OXT levels under several different conditions nor OXT messenger RNA expression in the paraventricular nucleus were different between the genotypes. Taken together, our data reveal a selective compensatory activation of the hypothalamic vasopressinergic, but not the oxytocinergic system, to maintain basal ACTH secretion and HPA system activity in Crhr1-/- mutants.

Different pathways of neurohormonal hypothalamic control of the adrenal cortex function in young and old rats.

The pathways of hypothalamic control of the adrenal cortex function were studied in the experiments on young and old male Wistar rats. Immunohistochemical, morphometric, densitometric and radioimmunoassay methods were used. It was shown that in young rats under stress vasopressin (VP) is released into the portal circulation and probably in this way stimulates ACTH and enhances secretion of corticosterone in the adrenal cortex. In old rats stress-reaction is delayed and less adequate compared to young animals. It seems likely that in old rats VP is secreted into the general circulation mainly via the posterior pituitary lobe (PP), exerting a direct influence on the adrenal cortex. The conclusion is made that in old rats regulation of the adrenal cortex function is realised via the pathway phylogenetically more ancient than in young animals.

Accelerative effect of olive oil on adrenal corticosterone secretion in rats loaded with single or repetitive immersion-restraint stress.

The present study was performed to clarify the effects of dietary oils on physiological and metabolic changes induced by a stress, using one-time or repetitive water-immersion of restrained rats (single or repetitive stress) as an experimental stress load. In rats fed any test diets containing 20%) of the mixture of tripalmitin, tristearin, and corn oil (PSC), olive oil (OLI). safflower oil (SAF), and linseed oil (LIS) with repetitive stress loading, body weight gains and food intakes were generally reduced. The weights of the thymus and spleen also declined, but the adrenal weights were enhanced. Particularly, the increase in the adrenal weight of rats given the OLI diet was greater than of rats supplied with other diets. When the rats were loaded with the single or repetitive stress, the concentrations of urea, lipid peroxide, and corticosterone in the plasma were increased in rats fed any of dietary oils. The rise of plasma corticosterone level was especially great in rats fed the OLI diet. The concentrations of total cholesterol (T-CHOL) and triglyceride (TG) in the plasma and liver generally tended to be higher in rats fed the OLI diet than in rats given the other diets with and without stress exposure. Plasma corticosterone concentration was correlated to the adrenal weight (r=0.87, p<0.05). This study showed that OLI especially enhanced the adrenal weight in rats exposed to the repetitive stress and further raised the increased secretion of adrenal corticosterone in rats loaded with the single or repetitive stress compared with the other oils. The mechanism explaining these actions of OLI was inferred to be related to the levels of T-CHOL and TG in the plasma and liver generally enhanced by stress.

Phytoestrogens alter adrenocortical function: genistein and daidzein suppress glucocorticoid and stimulate androgen production by cultured adrenal cortical cells.

Phytoestrogens influence a variety of biological processes. As 17beta-estradiol alters adrenocortical cell function, we examined whether the dietary phytoestrogens, genistein and daidzein, have related effects. In cultured human fetal and postnatal adrenal cortical cells, genistein and daidzein (both 0.4-40 micromol/L) decreased ACTH-stimulated cortisol production to basal levels (ED50, 1-4 micromol/L). In the adult adrenocortical cell line, H295, genistein, daidzein, and 17beta-estradiol (10 micromol/L) decreased cAMP-stimulated cortisol synthesis in a similar fashion. Neither genistein nor daidzein altered basal or ACTH-stimulated dehydroepiandosterone sulfate (DHEA-S) production in fetal adrenocortical cells, whereas in postnatal adrenocortical cells, DHEA and DHEA-S were markedly increased (ED50, 1-4 micromol/L). In H295 cells, basal and cAMP-stimulated DHEA production were similarly increased by the phytoestrogens and 17beta-estradiol. Genistein and daidzein did not affect the expression of steroid-metabolizing enzymes. However, genistein and daidzein specifically inhibited the activity of 21-hydroxylase (P450c21); the activities of other steroidogenic enzymes were not affected. Thus, phytoestrogens may decrease cortisol synthesis by suppressing the activity of P450c21 and, as a consequence, increase DHEA/DHEA-S synthesis by shunting metabolites away from the glucocorticoid synthetic pathway. Therefore, consumption of foods containing phytoestrogens may alter adrenocortical function by decreasing cortisol and increasing androgen production.

Hypothalamic oxytocin in the developing ovine fetus: interaction with pituitary-adrenocortical function.

Oxytocin (OT) stimulates corticotroph function in adult sheep, however, there is little information on OT synthesis and its potential involvement in hypothalamo-pituitary-adrenal (HPA) function in the fetus. The objectives of this study were to examine developmental changes in hypothalamic OT synthesis and to investigate the actions of OT on fetal corticotroph function. Hypothalami were removed at various stages of pre- and post-natal development. OT mRNA levels were measured using in situ hybridization. For in vitro studies, fetal pituitaries were removed on days 129 and 138 of gestation. Anterior pituitary cells were dispersed and cells were treated with different concentrations and combinations of OT, corticotrophin-releasing hormone (CRH), vasopressin (AVP) and cortisol. OT mRNA was present in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) by day 60 of gestation, and levels significantly increased at term. OT mRNA was present in parvocellular and magnocellular fields of the PVN. In vitro, OT stimulated adrenocorticotropin (ACTH) output in a dose-dependent fashion, but had no effect on cellular pro-opiomelanocortin (POMC) mRNA levels. There was no significant difference in corticotroph responsiveness to secretagogues between cells harvested at gestation day 129 or gestation day 138. Simultaneous exposure to CRH and OT stimulated increases in ACTH output that were significantly greater than for OT or CRH alone. However, no similar synergistic interaction existed between OT and AVP. Cortisol attenuated OT-stimulated ACTH output. In conclusion, hypothalamic OT mRNA increases at term and OT can stimulate ACTH output from fetal corticotrophs. Together, these data indicate that OT may be involved in the regulation of ACTH secretion in fetal sheep in late gestation.