Thyroid function during intermittent exposure to hypobaric hypoxia

Circulatory levels of triiodothyronine (T₃) and thyroxine (T₄) and their kinetics were studied in rabbits exposed to intermittent hypobaric hypoxia (5200 m, 395 mm Hg,PO₂ 83 mm Hg) 6 h daily for 5 weeks in a decompression chamber maintained at room temperature of 22°–24° C. Kinetics of T₃ and T₄ were studied on days 21 and 28 of hypoxic exposure. The T₃ and T₄ values were found to be significantly lower on day 8 of exposure to hypoxia compared to the pre-exposure values. The decreased levels were maintained throughout the entire period of hypoxic stress. The metabolic clearance rate, production rate, distribution space and extrathyroidal T₃ and T₄ pools were significantly decreased in animals under hypoxic stress compared to the control animals. The decline in thyroid hormone levels and their production in rabbits under hypoxic stress indicate an adaptive phenomenon under conditions of low oxygen availability.     

The age at onset of diabetes influences functional and structural changes in the pituitary-thyroid axis of streptozocin-diabetic male rats

Severe structural changes leading to marked alterations in secretory activity are known to occur in the pituitary-thyroid axis 1 month after induction of postpuberal streptozocin (SZ)-diabetes. However, SZ-diabetic rats of different age groups have not been compared, nor has the maturity of the pituitary and thyroid glands at the onset of diabetes been correlated with the type and evolution of functional and structural changes. We thus induced diabetes in 1-month (prepuberal or 3-month (postpuberal) old male rats and compared diabetic with control groups 4 and 8 months after SZ or saline injection. We determined: 1) pituitary and thyroid weights, 2) the basal plasma TSH, T₃, and T₄ concentrations, and 3) several morphometrical measurements in the pituitary and thyroid glands. After 4 months, 1) the pituitary and thyroid weights were decreased, 2) plasma TSH and T₃ were unchanged, plasma T₄ was reduced, and 3) the number of thyrotropes, degenerative changes of follicle cells, and colloid area were increased, the follicle cell height as well as the number of fused cold follicles decreased, and the follicle area was unchanged in diabetic compared with control rats. The lesions were more conspicuous in prethan in postpuberal diabetic animals. After 8 months, plasma TSH, T₃, and T₄ were decreased in diabetic compared with control rats. Except for the increased colloid area, all other lesions were similar, though more severe in prepuberal diabetic rats after 8 than 4 months. Few changes were found in postpuberal diabetic rats. We concluded that: 1) the effects of diabetes on the mature hypothalamus, pituitary, and thyroid gland seem to be reversed by aging and 2) the diabetic hypothalamic disorder we previously described appears to play a major pathogenetical role in the development of pituitary and thyroidal lesions.     

The influence of inorganic silicon (Si) on pituitary-thyroid axis

The influence of silicon-treatment on the levels of TSH and thyroid hormones was studied in rats. Concentrations of thyrotropin (TSH), triiodothyronine (T₃), and thyroxine (T₄) were estimated in sera of rats receiving per os a soluble silicon compound—sodium metasilicate nonahydrate (Na₂SiO₃·9H₂O), dissolved in the animals' drinking water. An increase in the TSH level in the tested group was observed, without statistically significant differences in T₃ and T₄ concentrations between the two groups of animals. The results provide evidence for the influence of silicon on the endocrine balance. They could also prove that this chemical element is capable of modifying the rate of some hormones' synthesis.     

Free and total thyroid hormones in humans at extreme altitude

Alterations in circulatory levels of total T₄ (TT₄), total T₃ (TT₃), free T₄ (FT₄), free T₃ (FT₃), thyrotropin (TSH) and T₃ uptake (T₃U) were studied in male and female sea-level residents (SLR) at sea level, in Armed forces personnel staying at high altitude (3750 m) for prolonged duration (acclimatized lowlanders, ALL) and in high-altitude natives (HAN). Identical studies were also performed on male ALL who trekked to an extreme altitude of 5080 m and stayed at an altitude of more than 6300 m for about 6 months. The total as well as free thyroid hormones were found to be significantly higher in ALL and HAN as compared to SLR values. Both male as well as female HAN had higher levels of thyroid hormones. The rise in hormone levels in different ALL ethnic groups drawn from amongst the southern and northern parts of the country was more or less identical. In both HAN and ALL a decline in FT₃ and FT₄ occurred when these subjects trekked at subzero temperatures to extreme altitude of 5080 m but the levels were found to be higher in ALL who stayed at 6300 m for a prolonged duration. Plasma TSH did not show any appreciable change at lower altitudes but was found to be decreased at extreme altitude. The increase in thyroid hormones at high altitude was not due to an increase in hormone binding proteins, since T₃U was found to be higher at high altitudes. A decline in TSH and hormone binding proteins and an increase in the free moiety of the hormones is indicative of a subtle degree of tissue hyperthyroidism which may be playing an important role in combating the extreme cold and hypoxic environment of high altitudes.     

Group X Secretory Phospholipase A2 Regulates the Expression of Steroidogenic Acute Regulatory Protein (StAR) in Mouse Adrenal Glands

We developed C57BL/6 mice with targeted deletion of group X secretory phospholipase A₂ (GX KO). These mice have ∼80% higher plasma corticosterone concentrations compared with wild-type (WT) mice under both basal and adrenocorticotropic hormone (ACTH)-induced stress conditions. This increased corticosterone level was not associated with increased circulating ACTH or a defect in the hypothalamic-pituitary axis as evidenced by a normal response to dexamethasone challenge. Primary cultures of adrenal cells from GX KO mice exhibited significantly increased corticosteroid secretion compared with WT cells. Conversely, overexpression of GX secretory phospholipase A₂ (sPLA₂), but not a catalytically inactive mutant form of GX sPLA₂, significantly reduced steroid production 30–40% in Y1 mouse adrenal cell line. This effect was reversed by the sPLA₂ inhibitor, indoxam. Silencing of endogenous M-type receptor expression did not restore steroid production in GX sPLA₂-overexpressing Y1 cells, ruling out a role for this sPLA₂ receptor in this regulatory process. Expression of steroidogenic acute regulatory protein (StAR), the rate-limiting protein in corticosteroid production, was ∼2-fold higher in adrenal glands of GX KO mice compared with WT mice, whereas StAR expression was suppressed in Y1 cells overexpressing GX sPLA₂. Results from StAR-promoter luciferase reporter gene assays indicated that GX sPLA₂ antagonizes StAR promoter activity and liver X receptor-mediated StAR promoter activation. In summary, GX sPLA₂ is expressed in mouse adrenal glands and functions to negatively regulate corticosteroid synthesis, most likely by negatively regulating StAR expression.     

Effect of selenium depletion and supplementation on the kinetics of type 1 5′-iodothyronine deiodinase and T3/T4 in rats

Presently, the effect of selenium (Se) deficiency and excess of Se (1 ppm) on the activity of selenoenzymes type 1 5′-iodothyronine deiodinase (5′-DI), glutathione peroxidase (GSH-Px), and level of thyroid hormones (T₃ and T₄) was studied in rats. Se levels in the serum and liver, T₃ and T₄ in the serum, GSH-Px levels in the liver, and 5′-DI activity in the liver/aorta/thyroid were estimated after 1, 2, and 3 mo of Se-deficient (0.02 ppm), Se-adequate (0.2 ppm), and Se-excess (1 ppm) diet feeding. All of these parameters decreased significantly in the Se-deficient group as compared to the adequate group. Within the deficient group, as the Se deficiency progressed, all of the parameters except 5′-DI decreased after 2 and 3 mo in comparison to 1-mo data. Thyroidal 5′-DI activity in Se deficiency showed the maximum increase. A significant increase was observed in all of the above parameters in the 1 ppm Se-supplemented diet group when compared with the adequate Se group; also, as the Se deposition increased within the Se-excess diet group, a significant increase was observed in all of the above parameters. However, as observed by others, the intake of excess of Se (i.e., 2 ppm in the diet) did not elevate the activities of selenoenzymes and thyroid hormones; rather, it had adverse effects. The present study concludes that Se supplementation at least up to 1 ppm enhances the selenoenzyme activities, and above this level, it may not be considered as an indicator of selenoenzyme activities.     

Protective role of Mangifera indica, Cucumis melo and Citrullus vulgaris peel extracts in chemically induced hypothyroidism

An investigation was made to evaluate the pharmacological importance of fruit peel extracts of Mangifera indica (MI), Citrullus vulgaris (CV) and Cucumis melo (CM) with respect to the possible regulation of tissue lipid peroxidation (LPO), thyroid dysfunctions, lipid and glucose metabolism. Pre-standardized doses (200 mg/kg of MI and 100 mg/kg both of CV and CM), based on the maximum inhibition in hepatic LPO, were administered to Wistar albino male rats for 10 consecutive days and the changes in tissue (heart, liver and kidney) LPO and in the concentrations of serum triiodothyronine (T₃), thyroxin (T₄), insulin, glucose, α-amylase and different lipids were examined. Administration of three test peel extracts significantly increased both the thyroid hormones (T₃ and T₄) with a concomitant decrease in tissue LPO, suggesting their thyroid stimulatory and antiperoxidative role. This thyroid stimulatory nature was also exhibited in propylthiouracil (PTU) induced hypothyroid animals. However, only minor influence was observed in serum lipid profile in which CM reduced the concentrations of total cholesterol and low-density lipoprotein-cholesterol (LDL-C), while CV decreased triglycerides and very low-density lipoprotein-cholesterol (VLDL-C). When the combined effects of either two (MI + CV) or three (MI + CV + CM) peel extracts were evaluated in euthyroid animals, serum T₃ concentration was increased in response to MI + CV and MI + CV + CM treatments, while T₄ level was elevated by the combinations of first two peels only. Interestingly, both the categories of combinations increased T₄ levels, but not T₃ in PTU treated hypothyroid animals. Moreover, a parallel increase in hepatic and renal LPO was observed in these animals, suggesting their unsafe nature in combination. In conclusion the three test peel extracts appear to be stimulatory to thyroid functions and inhibitory to tissue LPO but only when treated individually.     

Noise Induces Hypothyroidism and Gonadal Dysfunction Via Stimulation of Pineal–Adrenal Axis in Chicks

Noise is a world-wide problem that causes nervous, endocrine and cardiovascular disorders, and eventually health hazards in humans and animals. Objective of the current work is to investigate endocrine interaction in noise stress, which subsequently affects other endocrine functions including gonads in a poultry bird like chicks. Gravimetric, ultrastructural and hormonal status of the endocrine organs were examined to ascertain the effects of noise stress. Acute noise at 60 dB had no effect, but at 80 and 100 dB each for 3 h, increased pineal and serum serotonin, and adrenal and serum corticosterone, epinephrine and norepinephrine concentrations, without any change in thyroid or gonadal hormones. Chronic noise exposure at 60, 80 and 100 dB each for 6 h, daily for 7 days, drastically disturbed normal behavior, and quantum of food consumption and water intake. Chronic exposure also significantly decreased body weight including thyroid, ovary and testis weight, and increased adrenal weight. Noise stress caused ultrastructural changes leading to stimulations of pinealocytes (with abundance of rough endoplasmic reticulum and mitochondria), adrenocortical cells (enlarged nuclei and abundance of smooth endoplasmic reticulum) and adrenomedullary cells (enlarged nuclei with presence of chromaffin granules) were observed in noise stress. Additionally, pineal and serum serotonin, N-acetyl serotonin and melatonin, and adrenal and serum corticosterone, epinephrine and norepinephrine levels were significantly elevated following chronic noise exposure. Contrarily, thyroid activity was suppressed with atrophied thyroid follicles followed by declined levels of serum T₃ and T₄ with elevation of TSH level. Simultaneously, serum 17β-estradiol (E₂) and testosterone (T) concentrations were also significantly declined in all the doses of chronic noise. These changes were dose dependent of noise exposure. The findings suggest that (a) adrenal and pineal glands respond primarily to noise and secondarily act on other endocrine organs including gonads in chicks, (b) adrenal directly and/or indirectly causes thyroid and gonadal dysfunctions via pineal following noise exposure in chicks.     

The use of small subcutaneous transponders for quantifying thermal biology and torpor in small mammals

Remote measurements of body temperature (T_b) in animals require implantation of relatively large temperature-sensitive radio-transmitters or data loggers, whereas rectal temperature (T_rec) measurements require handling and therefore may bias the results. We investigated whether ∼0.1 g temperature-sensitive subcutaneously implanted transponders can be reliably used to quantify thermal biology and torpor use in small mammals. We examined (i) the precision of transponder readings as a function of temperature and (ii) whether subcutaneous transponders can be used to remotely record subcutaneous temperature (T_sub). Five adult male dunnarts (Sminthopsis macroura, body mass 24 g) were implanted with subcutaneous transponders to determine T_sub as a function of time and ambient temperature (T_a), and in comparison to thermocouple readings of T_rec. Transponder temperature was highly correlated with water bath temperature (r²=0.96–0.99) over a range of approximately 10.0–40.0 °C. Transponders provided reliable data (±0.6 °C) over the T_sub of 21.4–36.9 °C and could be read from a distance of up to 5 cm. Below 21.4 °C, accuracy was reduced to ±2.8 °C, but individual transponder accuracy varied. Consequently, small subcutaneous transponders are useful to remotely quantify thermal physiology and torpor patterns without having to disturb the animal and disrupt torpor. Even at T_sub<21.4 °C where the accuracy of the temperature readings was reduced, transponders do provide reliable data on whether and when torpor is used.     

Paracoccidioidomycosis in the region of Botucatu (state of São Paulo,Brazil). Evaluation of serum thyroxine (T4) and triiodothyronine (T3) levels and of the response to thyrotropin releasing hormone (TRH)

T₄, T₃ and TSH serum levels were measured in 25 patients with paracoccidioidomycosis. Thyroid T₃ reserves were measured on the basis of the increase in T₃ (T₃) 2 h after intravenous injection of 200 g TRH, and pituitary TSH reserves were measured on the basis of TSH increase (TSH) 20 min after the same injection. Twenty healthy volunteers with no history of thyroid disease were used as controls. When the two groups were compared, the following results were obtained: (a) there was no significant difference in mean T₄, T₃, TSH between groups; (b) reduced T₃ levels were detected more frequently in patients with paracoccidioidomycosis, especially among those with the acute form of the disease or with the severely disseminated chronic form. The results suggest the occurrence of a reduction in peripheral conversion of T₄ to T₃, but do not indicate the occurrence of hypothyroidism in any of its forms (thyroid, pituitary or hypothalamic).     

Hyperlipidemia and type I 5′-monodeiodinase activity

Male New Zealand White rabbits were divided into three groups: (I) control, (II) high-fat-diet (HFD) fed, and (III) HFD fed+selenium supplemented. After 3 mo of treatment, there was a significant increase in serum cholesterol and triglycerides in the HFD-fed group as compared to the control. However in the selenium (Se)-supplemented group, the levels of serum cholesterol and triglycerides were significantly less as compared to group II. HFD feeding resulted in decreased serum Se levels, but supplementation of dietary Se along with HFD, as in group III, showed an apparent increase in its levels. The Se-dependent glutathione peroxidase (GSH-Px) activity in the liver and the aorta increased significantly in HFD-fed animals and also showed an additional significant increase on Se supplementation. Both serum T₃ and T₄ levels showed a significant decrease on HFD feeding. However, supplementation of Se led to a significant increase in the levels of these parameters viz-à-viz HFD-fed animals. HFD feeding significantly decreased the activity of type I iodothyronine 5′-deiodinase (5′-DI) in the liver from group II rats. On supplementation of Se along with HFD, the activity increased in the liver. However, there was no significant change in its activity in the aorta. The 5′-DI activity in the thyroid showed an opposite trend in comparison with peripheral tissues (i.e., liver). The important finding of this study is that in the hyperlipidemic state, deiodinase in the thyroid behaves in a different manner as compared to its activity in extrathyroidal tissues.     

Abnormal regulation of adrenal function in rats with streptozotocin diabetes.

The factors that control adrenal steroid secretion and metabolism were investigated in rats made diabetic with Streptozotocin (65 mg/kg) and used one month after treatment. Diabetic animals possessed high resting levels of plasma corticosterone accompanied by adrenal hypertrophy; the showed an increased response to the stress of i.p. cold water injection. Moreover, the pituitaries of diabetic rats seemed to be releasing ACTH continuously and not storing it. Upon adrenal inhibition with Aminoglutethimide the expected increase in adrenal cholesterol and weight was of a smaller magnitude than in controls. The activity of liver enzymes that reduce ring A of corticosterone showed decreased activity in diabetics, which suggests that more corticosterone rather than its inactive metabolites were available to--but not able to suppress--the steroid feedback sites. The half-life of corticosterone in blood was similar in diabetes and controls. These results suggest that (a) diabetic animals were in a chronic stress condition; (b) the threshold for steroid feedback was less sensitive to variations in plasma corticosterone; (c) there is an abnormal peripheral disposal of corticosterone, but that other factors, besides the liver, regulate the clearance of the hormone from the circulation in the diabetic animals.     

The Effects of Triiodothyronine on Rat Testis: A Morphometric and Immunohistochemical Study

The aim of present study was to investigate the effects of 3,3′,5-triiodothyronine (T₃) on rat testis both morphometrically and immunohistochemically with determining of insulin-like growth factor I (IGF-I) expression. Adult male Wistar-albino rats used in the study were divided into two groups; control and T₃-treated groups. After T₃ treatment there was observed to be a decrease in testicular weights, diameters of seminiferous tubules and the number of sertoli cells, and an increase in the number of leydig cells (P<0.05). Some of the seminiferous tubule lumens of T₃ administrated rats had cellular debris. IGF-I was localized in sertoli cells, late spermatids and leydig cells of all groups. IGF-I immunoreactivity in T₃ treated rats was higher than in controls in all stages of the cycle of rat seminiferous epithelium, but the staining intensity of leydig cells were similar in both groups. In conclusion, the present results suggest that T₃ may modulate the testicular function by affecting IGF-I activity at the gonadal level.     

Early molecular events in the hippocampus of rats with streptozotocin-induced diabetes

In our study, we tried to find whether changes in expressions of inducible nitric oxide synthase (iNOS), corticosteroid (gluco-and mineralocorticoid) receptors (GRs and MRs, respectively), and bcl₂ protein within the early stages of streptozotocin (STZ)-induced diabetes in Wistar rats can be involved in hippocampal dysfunction. Expressions of iNOS and bcl₂ were studied using indirect immunofluorescence techniques, while GR and MR expressions were estimated using in situ mRNA hybridization. The concentrations of insulin, ACTH, and corticosterone in the blood serum were measured using ELISA kits. It was found that expression of iNOS in the CA2 and CA3 hippocampal areas increased significantly at day 3 after STZ injection, and corticosterone and ACTH levels in the serum increased at day 14. The iNOS expression was downregulated at day 14 of the development of diabetes. These changes were accompanied by significantly increased expression of GRs in the hippocampus. Neither bcl₂ nor MR expression increased in the CA2 and CA3 hippocampal areas within the examined period of the development of diabetes. Thus, we first obtained proof of noticeable early molecular events in the rat hippocampus related to experimental diabetes. These events may be linked with diabetes-associated cognitive decline observed in patients suffering from diabetes. Neirofiziologiya/Neurophysiology, Vol. 39, No. 6, pp. 498–502, November–December, 2007.     

Immunocytochemical localization of oviduct-specific glycoproteins in the oviductal epithelium from cows at follicular and luteal phases

An immunoelectron-microscopic and morphometric study was carried out on the anterior pituitary prolactin (PRL) cells of adult male Wistar rats treated with a combination of thyroidectomy and administration of L-thyroxine (T₄) and/or synthetic thyrotropin-releasing hormone (TRH) in order to clarify the effects of changes in the hypothalamus-pituitary-thyroid axis on the ultrastructure and function of PRL cells. After thyroidectomy, PRL cells underwent atrophy and hypofunction of their cell organelles, but these changes tended to be restored to their normal level by T₄ treatment. On the other hand, the administration of TRH to intact rats produced hypertrophy and hyperfunction in the PRL cells, although this treatment had no effect on the PRL cells of thyroidectomized rats. However, treatment with a combination of T₄ and TRH had a strong effect and led to hypertrophy and hyperfunction in the PRL cells of thyroidectomized rats. Serum and pituitary PRL levels were measured by radioimmunoassay (RIA) for a comparison with the morphological results. They correlated well with the morphological changes. These results indicate that TRH stimulates PRL secretion in the presence of thyroid hormone, and that the thyroid hormone plays an important role in the basic maintenance of PRL cell function and its reactivity to TRH.     

The action of a synthetic derivative of Met5-enkephalin-Arg6-Phe7 on behavioral and endocrine responses

The neuroendocrine and behavioral effects of Tyr-d-Ala-Gly-Phe-d-Nle-Arg-Phe (DADN), a more stable derivative of the endogenous opiate Met-enkephalin related peptide Met⁵-enkephalin-Arg⁶-Phe⁷ were investigated in mice. The behavioral experiments consisted of monitoring the horizontal (square crossing) and vertical (rearing) locomotion in the open field system. To evaluate the effect of the heptapeptide on the hypothalamo-pituitary-adrenal (HPA) axis, the plasma corticosterone level was measured. DADN induced dose-dependent increases in locomotion and rearing 30 min after intracerebroventricular injection and also elicited marked activation of the hormonal stress response. To elucidate the receptors involved in the mediation of these actions, animals were pretreated with the nonselective opioid antagonist naloxone, the selective κ-receptor antagonist nor-binaltorphimine or the μ₁-receptor blocker naloxonazine. Both the HPA activation and the behavioral responses were diminished by the preadministration of naloxone. Nor-binaltorphimine did not display a significant effect, while naloxonazine completely abolished the hyperactivity and the corticosterone elevation elicited by the analog. These findings suggest that μ-receptors predominate in the mediation of the neuroendocrine actions of DADN, while κ-receptors do not play a significant role.     

Thyroid hormones increase liver and muscle thermogenic capacity in the little buntings (Emberiza pusilla)

Thyroid hormones can increase energy expenditure and stimulate basal thermogenesis by lowering metabolic efficiency. In the present study, we examined the effects of thyroid hormones on basal heat production as well as on several physiological and biochemical measures indicative of thermogenic capacity to test our hypothesis that thyroid hormones stimulate increases in thermogenesis in little buntings. Little buntings that fed on thyroxine (T₄)–laced poultry food of 3 and 5 ppm concentrations showed increases in basal metabolic rate (BMR) during the 3-week acclimation. At the end, these buntings had lower body weights, higher levels of contents of mitochondrial protein, state 4 respiration and cytochrome c oxidase activity in liver and muscle, and higher concentrations of serum triiodothyronine (T₃) and T₄ compared to control buntings. These results support the argument that thyroid hormones play an important role in the regulation of thermogenic ability in buntings by stimulating mitochondrial respiration and enzyme activities associated with aerobic metabolism.     

Comparative in vitro responses of fetal, pregnant and non-pregnant rabbits' adrenal glands to steroidogenic agents

The in vitro secretion of aldosterone and corticosterone by the adrenal glands of fetal (day 30), pregnant and non-pregnant rabbits was examined under basal and stimulated conditions. In general, non-pregnant animals basally secreted less aldosterone than either pregnant or fetal rabbits, whereas basal corticosterone secretion by pregnant animals exceeded that of either fetal or non-pregnant animals. At similar doses of adrenocorticotropin (ACTH), fetal and pregnant adrenal glands produced comparatively more aldosterone than non-pregnant animals, while corticosterone secretion was accelerated to a greater degree in fetal rabbits than in the other groups. Angiotensin II had its greatest effect on the aldosterone secretory rates of fetal and non-pregnant animals without affecting corticosterone secretion in any group. Elevated potassium (K+) enhanced the secretory rates of aldosterone and corticosterone in fetal animals, while increasing only aldosterone secretion in non-pregnant rabbits. Serotonin accelerated aldosterone secretion in all animals, whereas it increased corticosterone secretion only in non-pregnant animals. These results suggest that (1) in fetal rabbits, the secretory rates of both aldosterone and corticosterone are regulated primarily by ACTH and to a much lesser extent by angiotensin II and K+, (2) the corticosterone secretory rates of pregnant and non-pregnant rabbits are controlled mainly by ACTH, and (3) aldosterone secretion by non-pregnant animals is regulated primarily by angiotensin II and secondarily by ACTH and K+, while in pregnant animals ACTH may be the primary regulator of aldosterone secretion as it is in the fetus.     

Selenium deficiency impairs corticosterone and leptin responses to adrenocorticotropin in the rat

Selenium deficiency causes oxidative stress and impairs steroidogenesis in vitro. Leptin is closely related to the hypothalamo-pituitary-adrenal (HPA) axis. Leptin inhibits the HPA axis at the central level while corticosteroids have been shown to stimulate leptin secretion in most studies. We hypothesized that oxidative stress impairs adrenal steroidogenesis and decreases leptin production in vivo. The goal of this study was to investigate in rats the effects of selenium deficiency and oxidative stress on adrenal function and on leptin concentrations. Weanling rats were fed a selenium-deficient (Se-) or selenium-sufficient (Se+) diet for 4-10 weeks. Selenium deficiency caused a marked decrease in liver (> or = 99%) and adrenal (> or = 81%) glutathione peroxidase (GPx) activities. Selenium deficiency did not affect basal and short-term adrenocorticotropin (ACTH) stimulated corticosterone or leptin concentrations. In contrast, after long-term ACTH stimulation, selenium deficiency caused a doubling in adrenal isoprostane content and blunted the increase in corticosterone and leptin concentrations observed in Se+ animals. Plasma leptin concentrations were 50% lower in Se- compared to Se+ animals following long-term ACTH. Our results suggest that oxidative stress causes a decrease in circulating corticosterone in response to ACTH, and, as a consequence, a decrease in plasma leptin concentrations.