Influence of vitamin D receptor gene polymorphisms on secondary hyperparathyroidism and bone density after kidney transplantation.

Secondary hyperparathyroidism and immunosuppressive treatments are the most important pathogenetic factors for bone disease after kidney transplantation. The aim of study was to compare the influence of vitamin D receptor (VDR) genotype on the PTH level and bone mineral density (BMD) in 67 patients, including 45 immunosuppressed with cyclosporine (CsA) and 22 with tacrolimus (Tac) versus 147 healthy volunteers. Two VDR polymorphisms: BsmI and FokI were assayed with RFLP-PCR. Scantibodies were utilized to evaluate 1-84 PTH. BMD was measured by DEXA. Hormone levels were measured on the third day and sixth month after transplantation. BMD was examined at the third and ninth month. The distribution of FokI genotype differed, but the BsmI genotypes did not differ between the transplant patients and the control group. All transplanted patients showed an elevated tPTH at the first examination. The highest PTH values, which were observed in bb genotype, significantly decreased after the transplant procedure. Patients with the FF genotype who were treated with CsA showed higher levels of tPTH than those with the Ff genotype. At 6 months, a decrease in tPTH occurred in both the CsA and the Tac patients. A low BMD at the third month was more frequent among patients of the BB genotype treated with CsA. The Z-score remained low at the third month and at the ninth month. In conclusion, kidney graft recipients show overrepresentation of the Ff genotype. Our preliminary data suggest that the bb genotype exhibits a protective effect on bone loss after renal transplantation.

The brain as a target organ of gonadal steroids.

Gonadal steroids have many effects in the central nervous system. Through a feedback mechanism, they influence the synthesis and release of hypothalamic gonadotropin-releasing hormone (GnRH) and/or pituitary gonadotropic hormones (luteinizing hormone, LH, and follicle stimulating hormone, FSH). Endogenous opioid peptides (EOPs) represent one of the key factors modulating the activity of sex steroids on the hypothalamus-pituitary-gonadal (HPG) axis. In particular, these peptides control the secretion of LH by inhibiting the activity of the hypothalamic neurons which produce GnRH. The EOP effect is dependent on the steroid hormone milieu, as shown by different responses to naloxone administration, both in animals and in humans. For the naloxone-induced increase in LH secretion to occur, relatively high levels of sex steroids are required. In humans, LH release is absent before sexual maturation. In fertile women, naloxone administration increases LH levels in the luteal phase but not in the follicular phase. In the postmenopausal period, naloxone has no effect on LH release; estrogen/progestin therapy does restore the LH response.

Acetyl-L-carnitine effect on pituitary and plasma beta-endorphin responsiveness to different chronic intermittent stressors.

The aims of the present study were: 1) to compare the effect of two different chronic intermittent stressors i.e. cold-swimming versus ether, on the pituitary opioidergic system; 2) to evaluate the response of pituitary and plasma beta-endorphin (beta-EP) to an acute stress in chronically stressed rats; and 3) to evaluate the effect of acetyl-l-carnitine treatment (10 mg/day/rat per os at night) on pituitary and plasma beta-EP changes induced by two different types of chronic stress. The stressors were applied twice a day for 10 days. Rats were killed either before, during or after the last swimming or ether stress session. beta-EP was measured by radioimmunoassay in anterior pituitary and in neurointermediate lobe extracts and in plasma. The following observations were made: 1) Chronic intermittent cold-swimming stress increased anterior pituitary contents and plasma beta-EP levels; 2) both chronic intermittent cold-swimming stress and ether stress caused an increase of neurointermediate lobe beta-EP contents; 3) as in control animals, rats exposed to chronic intermittent swimming stress reduced pituitary beta-EP contents and raised plasma beta-EP levels in response to the last acute swimming stress; 4) in contrast to control animals, rats exposed to chronic intermittent ether stress did not show any significant response of the pituitary-plasma opioidergic system to the last acute ether session; 5) the acetyl-l-carnitine treatment counteracted the changes evoked by chronic intermittent cold-swimming stress on the pituitary and plasma beta-EP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Modified dexamethasone and gonadotropin-releasing hormone agonist (Dx-GnRHa) test in the evaluation of androgen source(s) in hirsute women.

INTRODUCTION: Polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (COH) are heterogeneous disorders, in which excess of androgens may be caused by improper function of ovaries and/or adrenals. In many cases an overlap between ovarian and adrenal type of functional hyperandrogenism has been observed. The relationship between adrenal and ovarian metabolism in hyperandrogenic women is not totally known and etiologic diagnosis of female hyperandrogenism is often difficult. The aim of the present study was to evaluate the usefulness of combined Dexamethasone-Triptoreline testing in distinguishing ovarian and adrenal type of functional hyperandrogenism, and checking if the test could be shortened in order to economise it. MATERIALS AND METHODS: We have examined 57 women with androgen excess divided into two groups: ovarian (n = 42) and adrenal (n = 15) and 20 women with idiopathic hirsutism. There was also one patient suffering from Morris syndrome taken under examination just for curiosity. The blood for hormonal assay was taken in baseline conditions at 8.00 a.m. for LH, FSH, PRL, cortisol, T, DHEAS, 17OHP, E2. Dx was given for 4 days 0.5 mg p.o. every 6 hours. 8 hours after the last Dx administration, the blood was taken for 17OHP and T. Immediately after that Triptorelin 100 mg was given s.c. Then the blood was collected every 4 hours during 24 hours for 17OHP estimation. RESULTS: Decrease in T levels (from 1.65 +/- 0.52 to 0.73 +/- 0.25 ng/ml) after Dexamethasone administration was observed in adrenal group, which indicates adrenal glands as a source of excessive androgen production. No significant differences were seen in ovarian group. But in women from ovarian group supranormal 17OHP response after Triptoreline administration was seen: (ng/ml): at 8.00 am-0.68 +/- 0.44, 12.00--1.21 +/- 0.7*, 16.00--1.71 +/- 1.19*, 20.00--2.39 +/- 1.81*, 24.00--3.41 +/- 2.64*, 4.00--3.91 +/- 2.82*, 8.00--6.06 +/- 2.43* (*p < 0.01, **p < 0.001). Such a response is typical for women with well defined PCOS and other forms of functional ovarian hyperandrogenism and indicates ovary as a source of androgens. Significant differences were also noticed in idiopathic group: 8.00--0.31 +/- 0.09, 12.00--0.38 +/- 0.17, 16.00--1.41 +/- 0.62*, 20.00--1.52 +/- 0.97*, 24.00--1.89 +/- 0.83*, 4.00--2.17 +/- 0.83*, 8.00--1.83 +/- 0.71** (*p < 0.01). 17OHP levels did not change significantly during the whole test in adrenal group: 8.00--1.83 +/- 1.24, 12.00--1.91 +/- 1.37, 16.00--1.95 +/- 0.86, 20.00--2.19 +/- 0.93, 24.00--2.63 +/- 1.58, 4.00--2.56 +/- 1.78, 8.00--237 +/- 0.94. But patients from this group had exaggerated 17OHP response to ACTH (from 4.32 +/- 1.31 to 15.34 +/- 4.1 ng/ml). In patient suffering from Morris syndrome, after Triptoreline, serum 17OHP levels reminded on the same level as they were before drug administration. CONCLUSIONS: Combined Dx-Triptorelin test can be very useful to distinguish ovarian and adrenal type of functional hyperandrogenism. The number of times of blood collection for 17OHP can be reduced to 4 times a day (during 24 hours): at 8.00, 20.00, 24.00, 8.00.

1,25-dihydroxyvitamin D deficiency predicts poorer outcome after renal transplantation.

OBJECTIVE: To assess 1,25-dihydroxyvitamin D status and the effect of vitamin concentration on transplantation outcome in renal allograft recipients. PATIENTS AND METHODS: Ninety patients underwent renal transplantation between 2002 and 2005. All received alfacalcidol supplementation before surgery. 1,25-Dihydroxyvitamin D concentration was determined on day 3 posttransplantation and at 1-, 6-, 12-, 18-, and 24-month follow-up. RESULTS: Severe 1,25-dihydroxyvitamin D deficiency was noted in 83% of patients immediately posttransplantation. From 1 to 12 months thereafter, concentrations increased almost 3-fold, and remained constant to 24 months. In 50% of patients, the 1,25-dihydroxyvitamin D concentration reached a concentration of more than 30 pg/mL, similar to that in healthy volunteers; in the other 50%, the concentration reached 17.2 pg/mL. A high incidence of delayed graft function was observed in patients with 1,25-dihydroxyvitamin D deficiency (44% vs 6%). There was a negative correlation between the initial 1,25-dihydroxyvitamin D and serum creatinine concentrations at day 3 and month 6 (P < .03). Similarly, the 1,25-dihydroxyvitamin D concentration at 1 month was negatively correlated with creatinine concentration at months 1 through 24 (P < .01). Poor outcome was observed primarily in patients with 1,25-dihydroxyvitamin D deficiency; 2 patients developed cancer, 5 grafts were lost, and 4 patients died of cardiovascular events. CONCLUSIONS: 1,25-Dihydroxyvitamin D deficiency is highly prevalent in renal allograft recipients. Patients with 1,25-dihydroxyvitamin D deficiency are at greater risk of delayed graft function, and the graft is more likely to be lost. These findings suggest the necessity of adequate vitamin D supplementation both before and after transplantation.

[Function of endogenous opioid peptides and sex steroids at the level of the central nervous system]. / Dzialanie endogennych peptydów opioidowych i steroidów plciowych na poziomie osrodkowego ukladu nerwowego.

Gonadal steroids and beta-endorphin (beta-EP) (and probably other - EOP endogenous opioid peptides) play a role of the pivotal hormones involved in integration of several neurophysiological mechanisms. The reproductive system could be disturbed at hypothalamic level by interference of beta-EP and GnRH secretion and/or at pituitary level with response of gonadotropes to GnRH. Gonadal steroids, through a feedback mechanism, may exert similar effect on hypothalamus and/or pituitary. The action of EOP on the hypothalamo-pituitary-gonadal axis may be influenced by physiological and pathological changes in gonadal steroids during puberty, menstrual cycle in females, menopause, in case of idiopathic delayed puberty, in patients with gonadal dysgenesis or after castration. EOP seems to be "gonadostat" system that have a key role in the transmission of gonadal feedback signals to the brain.

Perimenopausal obesity.

In recent years perimenopausal obesity has attracted much attention, because it affects as many as 60% of women of menopausal age. The severe clinical implications of obesity directed our efforts to establish etiological factors and possible ways of treatment. It is clear that there are numerous conditions that underly perimenopausal obesity. Among these, genetic factors, neuropeptides, adrenergic nervous system activity and hormones play a role. Reproductive hormones are also an important factor, but their influence on adipose tissue is only indirect because there are no receptors for sex steroids in fatty tissue. Reports of hormone replacement therapy in women of postmenopausal age have come to different conclusions, so its influence on the etiology of perimenopausal obesity cannot be completely excluded. However, the potential benefit of this kind of treatment in female patients at menopausal age must always be considered.

Plasma insulin, cholecystokinin, galanin, neuropeptide Y and leptin levels in obese women with and without type 2 diabetes mellitus.

Obesity is an important factor predisposing to type 2 diabetes mellitus, especially for postmenopausal women. Experimental studies provided evidences that leptin, cholecystokinin (CCK), galanin (GAL), neuropeptide Y (NPY) and insulin are involved in feeding behaviour. The aim of the study was to evaluate their possible relationships in obese and diabetic women. Three groups of postmenopausal women (FSH > 30 mIU/ml) were evaluated: 8 diabetic (mean age 56.6 +/- 6.9 y, BMI 29.8 +/- 5.3 kg/m2), 10 obese non-diabetic (mean age 49.6 +/- 5.4 y, BMI 36.0 +/- 3.7 kg/m2) and 12 non-diabetic controls (mean age 52.7 +/- 3.5 y, BMI 27.3 1.9 kg/m2). For each patient BMI and WHR were measured and calculated. Blood samples were collected at 8:00 a.m. after an overnight fast. Plasma concentrations of FSH, leptin, CCK, GAL, NPY and insulin were determined using commercial RIA kits. Mean plasma NPY concentration was significantly higher in diabetic women than in controls (190.1 pg/ml +/- 85.4 vs 120.4 +/- 36.6). Compared to controls, mean plasma leptin level was significantly higher in obese non-diabetic women (32.9ng/ml +/- 9.2 vs 18.9 +/- 9.1). No significant differences were found between obese non-diabetic and diabetic women. In diabetic subjects positive correlations were found between: CCK and leptin (r= 0.8295; P= 0.011), CCK and insulin (r=0.7832; P=0.022), leptin and insulin (r=0.9302; P=0.001). In obese subjects a positive correlation between WHR and GAL (r= 0.6624; P= 0.037) and a negative between GAL and insulin (r= -0.6795; P= 0.031) were found. In controls positive correlations were found between WHR and CCK (r=0.6412; P=0.025), GAL and insulin (r=0.630; P=0.028) and negative between CCK and NPY (r = -0.6505; P= 0.022). Our results, ie higher mean plasma NPY levels in postmenopausal diabetic women and positive correlation of CCK with leptin and insulin, may suggest the role of these neuropeptides in metabolic disorders leading to type 2 diabetes mellitus.

[Hypoplasia of Leydig's cells as a cause of male pseudohermaphroditism]. / Hipoplazja komórek Leydiga jako przyczyna meskiego pseudohermafrodytyzmu.

A case of male hermaphroditism is presented. It complied with all traditional criteria of male hermaphroditism due to Leydig's cells hypoplasia (anomaly of the internal genitalia, karyotype 46, XY, presence of the testicular tissue, no response of the hypoplastic Leydig's cells to HCG stimulation with simultaneous dramatic decrease in their number in the interstitial tissue. Emphasis is on the marked difference in incomplete virilization of the external genitalia related to the occurrence of Leydig's cells insufficiency.

Influence of obesity and menopausal status on serum leptin, cholecystokinin, galanin and neuropeptide Y levels.

Obesity occurs in 60% of women after menopause and is characterized by an excess of adipose tissue that depends on several orexigenic (neuropeptide Y (NPY) stimulates carbohydrate ingestion, galanin stimulates fat intake) and anorectic (leptin, cholecystokinin (CCK)) factors. Both leptin and insulin can reduce hypothalamic NPY production and secretion. Behavior related to the consumption of food is probably attributed to the NPY-galanin signalling route. We investigated basal levels of serum leptin, CCK, galanin and NPY in 16 non-obese premenopausal women, in 15 obese premenopausal women (body mass index (BMI) 34.6 +/- 1.3 SD) and in ten obese postmenopausal women (BMI 34.7 +/- 1.5 SD) to determine the relationship between obesity, menopause and these neuropeptides. Obese premenopausal women had three-fold elevations of serum leptin (32.1 +/- 3.2 ng/ml) in comparison to non-obese premenopausal women (10.3 +/- 1.5 ng/ml), but similar levels to those in obese postmenopausal women (35.3 +/- 4.1 ng/ml). In all 44 patients and in both sub-groups of premenopausal and postmenopausal women, serum leptin exhibited a strong positive correlation with BMI (r = 0.8692, p < 0.0001; r = 0.8803, p = 0.0001; r = 0.8184, p = 0.0001, respectively). Serum galanin values showed a statistically significant increment in the obese postmenopausal group (51.1 +/- 8.1 pg/ml) compared to both premenopausal groups: the non-obese (34.9 +/- 5.8 pg/ml) and the obese (36.0 +/- 5.5 pg/ml). Non-obese menstruating women demonstrated NPY levels (175.0 +/- 12.8 pg/ml) significantly higher than those of obese premenopausal women (126.0 +/- 12.1 pg/ml) and obese postmenopausal women (138.1 +/- 15.4 pg/ml). CCK values showed no differences between non-obese and obese pre- and postmenopausal groups. Basal insulin values were elevated in both obese groups compared to non-obese premenopausal women. Significantly increased leptin and galanin levels in postmenopausal obese women coupled with decreased NPY levels revealed some changes in the neuropeptides regulating eating behavior, which may be the reason for the onset of postmenopausal obesity.

[Treatment of hyperandrogenic manifestations in polycystic ovary syndrome]. / Leczenie objawów hiperandrogenizmu w zespole wielotorbielowatych jajników.

Etiopathogenesis of the polycystic ovarian disease is not clarified. Therefore, optimum therapy of hyperandrogenic syndromes, menstrual and fertility disorders pose a difficult problem. Sequential therapy with estrogens and progestagens is of value in young women, who are not planning to conceive in order to reduce hirsutism and regulate menses. A reduction of hirsutism, acne and seborrhea is produced within 3 months. However, cessation of the treatment produces the symptoms of excessive androgen production. Another method is therapy with antiandrogens, especially cyproterone acetate. This drug inhibits androgens biosynthesis and has also peripheral activity. Spironolactone is another antiandrogen frequently used, but it is known as a primarily diuretic agent. It acts primarily at the androgen receptor sites. Other antiandrogens such as ketoconazole and flutamide are used less frequently. It has been shown, that cimetidine--known H2 receptor inhibitor--also decreases the symptoms of hyperandrogenism. However, cimetidine has not been used for the treatment of polycystic ovarian disease. In cases of enzymatic defects in adrenocortical steroido-synthesis glucocorticoids are used, mainly low doses of triamcinolone and dexamethasone. Other therapies are preferred in case of polycystic ovarian disease in women, who want to conceive. Clomiphene citrate and gonadotropins, mainly FSH, are used to induce ovulation. If pharmacotherapy does not produce ovulation, wedge resection of the ovaries must be performed.

Influence of dehydroepiandrosterone on platelet aggregation, superoxide dismutase activity and serum lipid peroxide concentrations in rabbits with induced hypercholesterolemia.

UNLABELLED: Special interest in the role of DHEA dates back to the finding of a correlation between low serum DHEA concentrations and a higher morbidity and mortality rate due to coronary diseases in humans. Animal studies with experimental atherosclerosis confirmed the anti-sclerotic effect of DHEA. The mechanism of DHEA action remains unclear. We determined the influence of dehydroepiandrosterone (DHEA) administration, a potential anti-atherogenic agent, on platelet aggregation, platelet superoxide dismutase (SOD) activity and serum lipid peroxide (LPO) levels in male rabbits fed on a normal and atherogenic diet. 44 adult male New Zealand white rabbits were divided into 4 groups: 1--control group fed on standard rabbit food, 2--fed on an atherogenic diet, 3--fed on an atherogenic diet with DHEA, 4--fed on standard food with DHEA. We detected blood platelet aggregation following (ADP) and collagen activation by means of photometry. Platelet SOD activity was detected by means of fluorometry determining the inhibition of adrenaline auto-oxidation. The serum LPO concentration was measured by means of the colorimetric method. The serum DHEA-S concentration was measured by means of RIA methods, and serum lipid levels were measured by means of Biomérieux manufactured kits. Results demonstrate that (1) elevated LPO concentrations in rabbits with hyperlipidemia did not decrease following DHEA administration. (2) In rabbits fed on a normal diet, DHEA caused a decrease of LPO, which emphasizes the positive influence of this steroid on the oxidative stress in healthy animals. Such a result was not seen in the group with severe hyperlipidemia. (3) Rabbits with hyperlipidemia demonstrated a significantly decreased SOD activity. (4) In healthy animals as well as in those with hyperlipidemia, DHEA administration caused an increase of platelet SOD activity, the main enzyme of the antioxidant defence system, which protects the organism against free radical damage (5) (DHEA had no influence on platelets aggregation in both tested groups). IN CONCLUSION: DHEA administration improves platelet SOD activity, which protects cells against oxidative damage. The hypothesis that DHEA administration leads to an increase in antioxidant potency requires further investigations.

Serum lipid peroxides and total antioxidant status in postmenopausal women on hormone replacement therapy.

Estradiol (E2) has antioxidant properties. The role of progestins in antioxidant defense is still unknown. We have evaluated the influence of E2 and E2 plus medroxyprogesterone acetate (MPA) on serum lipid peroxide (LPO) levels, a marker of free radical reactions, and serum total antioxidant status (TAS) in postmenopausal women. Subjects consisted of 26 women with surgical menopause, before and after 4 months of estrogen replacement therapy (ERT; E2), and 54 women with natural menopause on hormone replacement therapy (HRT; E2 plus MPA). Forty premenopausal women served as a control group. Serum E2 was estimated by radioimmunoassay, follicle-stimulating hormone by IRMA methods, LPO and TAS by colorimetric methods. Before therapy, LPO levels in the postmenopausal women were significantly higher (p < 0.001) than in the control group. After both ERT and HRT, LPO decreased significantly and did not differ between both groups and the control group. TAS was significantly lower in postmenopausal women (p < 0.001) than in the control group before therapy. After both ERT and HRT, TAS increased significantly and did not differ between both groups and the control group. We conclude that oxidative stress is increased after menopause. ERT and HRT inhibit the generation of free radicals and raise antioxidant potential to the levels found in premenopausal women. MPA did not influence the antioxidant action of E2.

Serum lipid peroxide levels and erythrocyte glutathione peroxidase and superoxide dismutase activity in premenopausal and postmenopausal women.

Free radical reactions are involved in processes connected with aging. Estradiol acts as antioxidant and free radical scavenger, but the mechanism of this action remains unknown. Estradiol has a hydroxyphenolic structure and may donate hydrogen atoms to lipid peroxyradicals to terminate chain reactions. There are a few reports concerning the influence of estradiol on natural antioxidant enzyme activity, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). The aim of this study was to estimate the relationship between the levels of estradiol and lipid peroxide (LPO), a marker of membrane lipid peroxidation, and the correlation between estradiol and erythrocyte SOD and GSH-Px activity. The study included 13 premenopausal and 13 postmenopausal healthy women. Serum levels of estradiol, follicle-stimulating hormone (FSH) and LPO, and erythrocyte SOD and GSH-Px activity were estimated in all subjects. Premenopausal women revealed significantly higher estradiol levels and lower LPO concentrations, as well as significantly higher GSH-Px activity than the postmenopausal group. SOD activity did not differ between the two groups. There was a negative correlation between serum estradiol and LPO levels as well as a positive correlation between estradiol and GSH-Px activity. These results support the hypothesis that estradiol exerts its antioxidant action not only through its chemical structure but probably also through its influence on natural cellular antioxidant enzyme activity.

Melatonin treatment delays reproductive aging of female rat via the opiatergic system.

In female rat age-related reproductive decline is accompanied by progressive impairment of the neuroendocrine mechanisms that regulate LH secretion. The biosynthetic activity of the pineal gland is markedly depressed and the nocturnal secretion of melatonin decreases significantly. The aim of the present study was to evaluate whether the nocturnal administration of melatonin via the drinking water (0.4 micrograms/ml) throughout the course of aging from 14 to 24 months of age could (1) influence the age-related changes that occur in basal serum levels of LH and in the LH response to GnRH or to naloxone stimulation at 16, 18 and 20 months of age, and (2) delay the onset of the postreproductive constant estrous-anovulatory state as evaluated by the daily recording of vaginal smears and by occurrence of polyfollicular ovaries at 24 months of age. Our results demonstrate that melatonin replacement delays the increase in LH serum levels and the decrease in LH response to GnRH that occur in 18-month-old control animals. Furthermore, they show that melatonin treatment prevents the loss of LH response to naloxone manifested in control rats between 16 and 20 months of age. Melatonin also appears to prevent the progressive increase in the monthly occurrence of estrus phases as well as to decrease the number of rats with polyfollicular ovaries at 24 months of age in comparison to control animals. These results suggest that the age-related decrease in circulating melatonin during the night may contribute to the reproductive decline of aging, and that this effect may involve the central opioid system.

Effect of different chronic intermittent stressors and acetyl-l-carnitine on hypothalamic beta-endorphin and GnRH and on plasma testosterone levels in male rats.

Chronic stress affects the reproductive function by modifying the neuroendocrine homeostasis. The aim of the present study was to clarify the neuroendocrine and the gonadal changes following chronic intermittent stress in male rats and the action of a neuroactive drug, acetyl-l-carnitine (ALC). The effect of two different stressors, cold water swimming or ether, on central beta-endorphin (beta-EP) and GnRH contents, and on plasma testosterone levels was investigated. In addition, the response to an acute stress in chronically stressed rats, treated or untreated with ALC (10 mg/day/rat p.o.), was evaluated. The stressors were applied twice a day for 10 days, and rats were killed before, during and after the last stress session. Mediobasal hypothalamus (MBH) beta-EP and GnRH contents, and plasma testosterone levels were evaluated by radioimmunoassay. The following results were obtained: (1) both chronic swimming and ether stress caused a decrease in hypothalamic beta-EP contents; (2) MBH GnRH contents increased after chronic swimming stress but not after ether stress; (3) chronic swimming stress induced a twofold decrease in plasma testosterone levels, while no changes were observed after ether stress; (4) the treatment with ALC prevented the decrease in plasma testosterone levels after chronic swimming stress, and (5) acute stress in chronically stressed animals caused an increase in MBH-beta-EP. The present data showed that chronic swimming stress reduces the reproductive capacity and impairs the capacity to respond to the acute stress and that ALC modulates the hormonal changes to physical stress and prevents the antireproductive effect of chronic cold swimming.