Serotonin and melatonin secretion and metabolism in patients with liver cirrhosis.

INTRODUCTION: Hepatic encephalopathy is one of the symptoms of liver failure. The exact causes of encephalopathy are complex and still unclear. Apart from elevated blood ammonia levels, the role of numerous other factors is being considered. OBJECTIVES: The aim of the study was to determine the serum level of serotonin and melatonin and the urinary excretion of their metabolites (5-hydroxyindoleacetic acid [5-HIAA] and 6-sulfatoxymelatonin [6-HMS]) in patients with various stages of liver cirrhosis. PATIENTS AND METHODS: The study comprised 75 patients with alcohol-induced liver cirrhosis and 25 healthy subjects (control group). Based on the Child-Pugh classification, 3 groups of 25 patients each were distinguished - group A, B, and C with grade A, B, and C of liver failure, respectively. Blood samples were drawn at fasting at 9 a.m., and 24-hour urine collection was performed. Immunoenzymatic assays were used to determine serum melatonin and serotonin levels as well as urine 5-HIAA and 6-HMS concentrations. RESULTS: Serum serotonin levels were 159.8 ± 23.1 ng/ml in controls, 179.3 ± 21.1 ng/ml in group A (P >0.05), 143.2 ± 22.8 ng/ml in group B (P >0.05), and 114.5 ± 37.6 ng/ml in group C (P <0.01). Serum melatonin levels were 10.6 ± 1.7 in controls, 31.2 ± 9.8 pg/ml in group A (P <0.01), 49.8 ± 12.2 pg/ml in group B (P <0.001), and 94.8 ± 22.6 pg/ml in group C (P <0.001). Urinary 5-HIAA excretion was 5.9 ± 2.1 mg/24 h in controls, 5.9 ± 1.9 mg/24 h in group A (P >0.05), 4.8 ± 1.2 mg/24 h in group B (P >0.05), and 4.6 ± 1.4 mg/24 h in group C (P <0.05). Urinary 6-HMS excretion was 26.6 ± 15.1 µg/24 h in controls, 23.2 ± 7.9 µg/24 h in group A (P >0.05), 18.3 ± 10.6 µg/24 h in group B (P >0.05), and 6.5 ± 3.6 µg/24 h in group C (P <0.001). CONCLUSIONS: Disturbances in serotonin and melatonin homeostasis observed in patients with liver cirrhosis may be associated with advanced encopaholopathy.

Decreased melatonin nocturnal concentrations in hemodialyzed patients.

OBJECTIVES: In spite of broad interest, intensive studies on function of melatonin have not yielded much information about relationships between this hormone and kidneys in health, and particularity, in disease. There are only a few studies dealing with melatonin concentrations in renal diseases, mainly performed in hemodialyzed patients with end-stage renal disease (ESRD). Moreover, the most melatonin assays were performed during the daytime, and the results are conflicting. Therefore, the aim of the present study was to determine the circadian melatonin profiles in patients ESRD before and after hemodialysis. MATERIAL AND METHODS: Thirty patients (19 males and 11 females) with ESRD undergoing dialysis, aged 22 to 64 years (mean+/-SEM: 49.1.0+/-1.9 years) were included in the study. The control group consisted of 20 healthy volunteers (13 males and 7 females) aged 35 to 55 years (mean+/-SEM: 46.2+/-1.4 years) matched according to sex and age. Blood samples were collected on the day preceding hemodialysis and one day following dialysis at 08:00, 12:00, 16:00, 20:00, 24:00, 02:00, 04:00, and 08:00 h. Melatonin concentration was measured by enzyme immunoassay. RESULTS: In patients with renal insufficiency undergoing dialysis mean melatonin nocturnal concentrations were significantly lower then those in healthy volunteers. The presence of the circadian rhythm in melatonin concentrations (although of significantly lower nocturnal amplitude) was detected only in 8 patients with renal failure undergoing hemodialysis, whereas in remaining 22 patients no such rhythm was found. Hemodialysis did not influence melatonin concentrations. CONCLUSIONS: The mechanism of depressed melatonin concentrations in hemodialyzed patients observed in our study remains unclear. However, it seems possible that decline in melatonin levels is due to impairment in adrenergic function that occurs in renal failure. Because the studies on the melatonin secretion in chronic renal failure bring about conflicting results, the relationship between renal diseases and melatonin secretion needs further investigations.

Serum melatonin circadian profiles in women suffering from cervical cancer.

Although there is an increasing evidence that the pineal gland may play a role in human malignancy, the studies on melatonin concentrations in different types of malignant tumors brought about controversial results. However, changes in melatonin concentrations have been observed in some types of human malignant tumors. Therefore, we decided to study the circadian melatonin rhythm in patients suffering from cervical cancer in different stages of progression and to compare them with those in subjects free from neoplastic disease. A total of 45 women were analyzed in this study. The subjects were divided into two groups. The first group consisted of 31 patients [mean age 52.1 +/- 1.8 yr (mean +/- S.E.M.), range 32-77 yr] with cervical cancer in various stages of the disease. The second group consisted of 14 healthy volunteers [mean age 53.5 +/- 2.0 yr (mean +/- S.E.M.), range 42-63] who served as the control group. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00, and 08:00 hours. Melatonin concentration was measured by immunoenzymatic method. There were significant differences in circadian melatonin profiles as well as in the area under curve among the two studied groups. Melatonin concentrations were significantly lower in cancer patients in comparison with healthy individuals. Taking into consideration stage of the cervical cancer significantly lower melatonin secretion has been found in all subgroups of patients in comparison with that of tumor-free control group. Additionally, nocturnal melatonin concentrations as well as area under curve were significantly lower in advanced stage of cancer (stages 3 and 4) in comparison with patients with preinvasive cancer (stage 0) at 24:00, 02:00, and 04:00 hours and patients with stage 1 disease at 02:00 and 04:00 hours. The results of the present study indicate that the presence of cervical cancer influences melatonin levels in women. Moreover, stage dependence in reduction of melatonin concentrations has been found.

Melatonin circadian rhythm in women with idiopathic hyperprolactinemia.

OBJECTIVES: Relationship between melatonin and prolactin has been suggested on the basis of both experimental and clinical studies. However, there are scarce and controversial data concerning melatonin concentrations in hyperprolactinemic patients. Therefore, the aim of the present study was to evaluate the circadian rhythm of melatonin in female patients suffering from hyperprolactinemia. MATERIAL AND METHODS: The study was performed on 28 women aged 17-58 years (mean+/-SEM: 30.5+/-1.8 years) suffering from idiopathic hyperprolactinemia and 14 healthy volunteers aged 20-50 years (mean+/-SEM: 36.4+/-3.0 years) with normal prolactin levels. Blood samples for measurements of serum melatonin and prolactin concentrations were collected at 08:00, 12:00, 16:00, 20:00, 24:00, 02:00, 04:00, 06:00, and 08:00 h. Melatonin and prolactin concentrations were measured by enzyme immunoassay. RESULTS: Significant increase in melatonin serum concentrations was also observed in hyperprolactinemic patients in comparison with healthy volunteers during the night. Similar increase was also observed in the area under curve of melatonin concentrations. However, no correlation was found between prolactin and melatonin concentrations in any examined time points. CONCLUSION: The results of the present study confirm suggestions of the presence of the relationship between melatonin and prolactin secretion.

Circadian serum melatonin profiles in patients suffering from chronic renal failure.

OBJECTIVES: In spite of broad interest, intensive studies on function of melatonin have not yielded much information about relationships between this hormone and kidneys in health, and particularity, in disease. Very little is known about the circadian plasma melatonin concentrations in patients with chronic renal failure (CRF). There are only a few studies dealing with melatonin concentrations in renal diseases, mainly performed in hemodialyzed patients with end-stage renal disease (ESRD). Moreover, the most melatonin assays were performed during the daytime, and the results are conflicting. Therefore, the aim of the present study was to determine the circadian melatonin profiles in patients with different stages of CRF. MATERIAL AND METHODS: Twenty four patients (13 males and 11 females) with CRF aged 35 to 58 years (mean+/-SEM: 47.0+/-1.6 years) were included in the study. Patients were divided into two groups: group 1 -- patients with compensated CRF (serum creatinine: 2.0-5.0 mg/dL), group 2 -- patients with ESRD (serum creatinine: > 8,0 mg/dL). The control group consisted of 20 healthy volunteers (10 males and 10 females) aged 35 to 55 years (mean+/-SEM: 46.0+/-1.5 years) checked not to have renal failure [serum creatinine: 0.8-1.4 mg/dL], and matched according to sex and age. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 24:00, 02:00, 04:00, and 08:00 h. Melatonin concentration was measured by enzyme immunoassay. RESULTS: In both groups of patients with chronic renal failure, i.e. in patients with compensated disease and in patients with end-stage renal disease melatonin nocturnal concentrations were significantly lower then those in healthy volunteers. Moreover, in patients with compensated renal failure also day-time melatonin concentrations were significantly depressed. Area under curve was significantly lower in both groups of patients in comparison with the control group. CONCLUSIONS: The mechanism of depressed melatonin concentrations in CRF observed in our study remains unclear. However, it seems possible that decline in melatonin levels is due to impairment in adrenergic function that occurs in CRF. Because the studies on the melatonin secretion in CRF bring about conflicting results, the relationship between renal diseases and melatonin secretion needs further investigations.

[Modulation of hypothalamo-pituitary axis by stress during labor]. / Modulacja osi podwzgórze-przysadka podczas stresu zwiazanego z porodem w ciazy donoszonej.

OBJECTIVES: The present study is aimed to investigate the function of hypothalamo-pituitary-adrenal axis of women during late pregnancy and term labor. DESIGN: Levels of hormones were measured in blood of 34 women undergoing spontaneous labor and elective cesarean section, 2 days before and after delivery, and during labour. Additionally, blood from the umbilical vein and artery was also collected. MATERIALS AND METHODS: We have evaluated changes in corticotropin releasing hormone (CRH), adrenocorticotropin (ACTH) and dehydroepiandrosterone (DHEA) in vein blood of 34 subjects. The concentrations of hormones were measured by dint of RIA method. RESULTS: No significant correlation was found between hormone measurements and fetal outcome. CRH level in the umbilical vein was higher than in the umbilical artery, suggesting the placental origin of hormone. Prepartum CRH concentration was significantly higher in the group of spontaneously delivered patients. There were no correlations between CRH levels and ACTH and DHEA concentration in mother's blood plasma. In fetuses, higher prepartum CRH concentrations resulted in elevated levels of ACTH. No changes were found in DHEA concentration, in both mother and fetus. CONCLUSIONS: These results suggest that placental CRH may modulate a fetus's pituitary but not mother's. The observed high levels of this hormone play an important role mainly in preparation of mother and fetus for delivery.

Melatonin concentrations in patients with large goiter before and after surgery.

OBJECTIVES: Surgical removal of a very large goiter may traumatize adjacent anatomical structures. The manipulations that involve superior cervical ganglia may alter melatonin secretion. To test this hypothesis we decided to study diurnal serum melatonin profiles in patients with a very large goiter before and after the surgery. MATERIAL AND METHODS:The study was performed on 10 women (mean age-46.5+/-1.6 years; mean+/-SEM; range 39-54 years) with very large non-toxic nodular goiter (mean thyroid volume-125.8+/-25.9 cm (3); mean+/-SEM; range 82.6-326.7 cm(3)). Diurnal serum melatonin profiles were estimated two days before the operation and 10 days after the surgery. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00 and 08:00 h. Melatonin concentration was measured using RIA kit. RESULTS: Nocturnal serum melatonin concentrations (at 24, 02, and 04 hours) were significantly higher after the surgery than before the operation. CONCLUSIONS: Very large goiter may compress the superior cervical ganglia altering indirectly the melatonin synthesis. It cannot be excluded, however, that the presence of the large goiter in some other way affects melatonin secretion.

Serum melatonin circadian profile in women suffering from the genital tract cancers.

OBJECTIVES: Although there is increasing evidence that the pineal gland may play a role in human malignancy, the studies on melatonin concentrations in different types of malignant tumors brought about controversial results. However, changes in melatonin concentrations have been observed in some types of human malignant tumors. Therefore we decided to study the circadian melatonin rhythm in patients suffering from malignant tumors of the female genital tract, and to compare them with subjects free from neoplastic disease (healthy volunteers and patients with myomatous uterus). MATERIAL AND METHODS: A total of 46 women were analyzed in this study. The subjects were divided into 3 groups. The first group consisted of 23 patients with malignant tumors of the genital tract (mean age 50.3+/-2.2 years; mean+/-SEM, range 32-77 years). The second group consisted of 16 healthy volunteers (mean age 50.9+/-1.8 years; mean+/-SEM, range 42-63) who served as the first control group, whereas the third group consisted of 7 subjects who suffered from myomatous uterus (mean age 45.7+/-2.3 years; mean+/-SEM, range 39-56) and served as the second control group without malignancy. Blood samples were collected at 08:00, 12:00, 16:00, 20:00, 22:00, 24:00, 02:00, 04:00, 06:00 and 08:00 h. Melatonin concentration was measured using RIA kit. RESULTS: There were no significant differences in circadian melatonin profiles among the three groups studied. Taking into consideration the type of tumor of the genital tract, significantly lower melatonin secretion has been found in patients with endometrial cancer in comparison with tumor-free control groups, whereas no significant differences in melatonin secretion have been observed between tumor-free control groups and patients with invasive ovarian cancer and squamous cervical cancer. However, significant differences have been observed between endometrial cancer and invasive ovarian cancer. CONCLUSION: Its seems probable that melatonin concentrations in human malignancy may, at least partly, depend on hormone dependency of the particular type of tumor.