Molecular Regulation of the CNS by Vitamin D.

Vitamin D is a lipid-soluble vitamin that can be found in some foods. It is also produced endogenously (in the presence of ultraviolet light), transported through the blood to the targets organs and this is the reason to consider vitamin D as a hormone. It is known that vitamin D has genomic and non-genomic effects. This review is focused mainly on the vitamin D receptors, the importance of vitamin D as a neuromodulator, the role of vitamin D in the pathophysiology of devastating neurological disorders such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and the benefit of vitamin D and its derivates in alleviating these disorders.

Steroids, steroid associated substances and gestational diabetes mellitus.

As gestational diabetes mellitus (GDM) is both a frequent and serious complication, steroid levels in pregnancy are extremely elevated and their role in pregnancy is crucial, this review focuses on the role of steroids and related substances in the GDM pathophysiology. Low SHBG levels are associated with insulin resistance and hyperinsulinemia, while also predicting a predisposition to GDM. Other relevant agents are placental hormones such as kisspeptin and CRH, playing also an important role beyond pregnancy, but which are synthesized here in smaller amounts in the hypothalamus. These hormones affect both the course of pregnancy as well as the synthesis of pregnancy steroids and may also be involved in the GDM pathophysiology. Steroids, whose biosynthesis is mainly provided by the fetal adrenal glands, placenta, maternal adrenal glands, and both maternal and fetal livers, are also synthesized in limited amounts directly in the pancreas and may influence the development of GDM. These substances involve the sulfated ?5 steroids primarily acting via modulating different ion channels and influencing the development of GDM in different directions, mostly diabetogenic progesterone and predominantly anti-diabetic estradiol acting both in genomic and non-genomic way, androgens associated with IR and hyperinsulinemia, neuroactive steroids affecting the pituitary functioning, and cortisol whose production is stimulated by CRH but which suppresses its pro-inflammatory effects. Due to the complex actions of steroids, studies assessing their predominant effect and studies assessing their predictive values for estimating predisposition to GDM are needed.

A method for determination of one hundred endogenous steroids in human serum by gas chromatography-tandem mass spectrometry.

Steroid profiling helps various pathologies to be rapidly diagnosed. Results from analyses investigating steroidogenic pathways may be used as a tool for uncovering pathology causations and proposals of new therapeutic approaches. The purpose of this study was to address still underutilized application of the advanced GC-MS/MS platform for the multicomponent quantification of endogenous steroids. We developed and validated a GC-MS/MS method for the quantification of 58 unconjugated steroids and 42 polar conjugates of steroids (after hydrolysis) in human blood. The present method was validated not only for blood of men and non-pregnant women but also for blood of pregnant women and for mixed umbilical cord blood. The spectrum of analytes includes common hormones operating via nuclear receptors as well as other bioactive substances like immunomodulatory and neuroactive steroids. Our present results are comparable with those from our previously published GC-MS method as well as the results of others. The present method was extended for corticoids and 17alpha-hydroxylated 5alpha/ß-reduced pregnanes, which are useful for the investigation of alternative "backdoor" pathway. When comparing the analytical characteristics of the present and previous method, the first exhibit by far higher selectivity, and generally higher sensitivity and better precision particularly for 17alpha-hydroxysteroids.

May circulating steroids reveal a predisposition to intrahepatic cholestasis of pregnancy in non-pregnant women?

Intrahepatic cholestasis of pregnancy (ICP) is a frequent liver disorder, mostly occurring in the third trimester. ICP is not harmful to the mothers but threatens the fetus. The authors evaluated steroid alterations in maternal and mixed umbilical blood to elucidate their role in the ICP development. Ten women with ICP were included in the study. Steroids in the maternal blood were measured by Gas Chromatography-Mass Spectrometry (GC-MS) (n=58) and RIA (n=5) at the diagnosis of ICP, labor, day 5 postpartum, week 3 postpartum and week 6 postpartum. The results were evaluated by ANOVA consisting of the subject factor, between subject factors ICP, gestational age at the diagnosis of ICP and gestational age at labor, within-subject factor Stage and ICP × Stage interaction. The 17 controls were firstly examined in the week 36 of gestation. ICP patients showed reduced CYP17A1 activity in the C17,20 lyase step thus shifting the balance between the toxic conjugated pregnanediols and harmless sulfated 5alpha/beta-reduced-17-oxo C19 steroids. Hence, more toxic metabolites originating in maternal liver from the placental pregnanes may penetrate backward to the fetal circulation. As these alterations persist in puerperium, the circulating steroids could be potentially used for predicting the predisposition to ICP even before next pregnancy.

Neuroactive steroids in periphery and cerebrospinal fluid.

Some peripheral steroids penetrate the blood-brain barrier (BBB), providing at least substances for the CNS steroid metabolome. That is why the predictive value of the peripheral steroids appears to be comparable with that of the cerebrospinal fluid (CSF) steroids. The concentrations of the CSF steroids are pronouncedly lower in comparison with the ones in circulation. The available data indicate that the levels of pregnenolone sulfate substantially increase in the rat brain tissue after the administration of pregnenolone into the circulation. In the human circulation there are about two orders of magnitude higher levels of pregnenolone sulfate compared to the free pregnenolone. Our data show insignificant correlation between CSF and serum pregnenolone, but a borderline one between CSF pregnenolone and serum pregnenolone sulfate. Therefore in humans, the circulating pregnenolone sulfate might be of an importance for pregnenolone concentration in the CNS. In contrast to free pregnenolone, dehydroepiandrosterone (DHEA) in the CSF correlates with both unconjugated and conjugated DHEA in the serum. These data as well as the low C17-hydroxylase-C17,20-lyase activity in the CNS might indicate that DHEA levels in the CNS are influenced by peripheral levels of DHEA and its sulfate. According to the information, available part of the neurosteroids may be synthesized de novo in the CNS, but substantial part of the steroid metabolites may be also synthesized in the CNS from the steroid precursors or directly transported through BBB from the periphery. The processes mentioned above may be complimentary in some cases. Brain synthesis may provide minimal level of neurosteroids, which are indispensable for the CNS functions. Thus, brain steroids of peripheral origin may reflect various physiological situations or even pathologies. This article is part of a Special Issue entitled: Neuroactive Steroids: Focus on Human Brain.

Reduced progesterone metabolites in human late pregnancy.

In this review, we focused on the intersection between steroid metabolomics, obstetrics and steroid neurophysiology to give a comprehensive insight into the role of sex hormones and neuroactive steroids (NAS) in the mechanism controlling pregnancy sustaining. The data in the literature including our studies show that there is a complex mechanism providing synthesis of either pregnancy sustaining or parturition provoking steroids. This mechanism includes the boosting placental synthesis of CRH with approaching parturition inducing the excessive synthesis of 3beta-hydroxy-5-ene steroid sulfates serving primarily as precursors for placental synthesis of progestogens, estrogens and NAS. The distribution and changing activities of placental oxidoreductases are responsible for the activation or inactivation of the aforementioned steroids, which is compartment-specific (maternal and fetal compartments) and dependent on gestational age, with a tendency to shift the production from the pregnancy-sustaining steroids to the parturition provoking ones with an increasing gestational age. The fetal and maternal livers catabolize part of the bioactive steroids and also convert some precursors to bioactive steroids. Besides the progesterone, a variety of its 5alpha/beta-reduced metabolites may significantly influence the maintenance of human pregnancy, provide protection against excitotoxicity following acute hypoxic stress, and might also affect the pain perception in mother and fetus.

Sulphates of 3beta-hydroxy-5-ene steroids in women with epilepsy.

Epilepsy is associated with various reproductive disorders and some antiepileptic drugs also influence the steroid metabolism. There is only limited data concerning the role of steroid sulphates in human epilepsy. Moreover, the substitution treatment with therapeutic substances also improves cognitive functions in humans. Therefore, we evaluated the balance between free and Delta5 sulphated steroids in women with epilepsy on various antiepileptic drugs. The study included 28 patients (17.0-51.0 years), with generalized (n=16) or catamenial epilepsy (n=12) followed in the follicular (FP) and luteal (LP) phases of menstrual cycle. Fifteen patients were on monotherapy and 13 were on polytherapy with 2 or 3 drugs. RIA was used for the steroid analyses. Statistical evaluation was done by Mann-Whitney tests and multivariate regression with reduction of dimensionality (Orthogonal Projections to Latent Structures, O2PLS). The final O2PLS model found a single significant predictive component extracting the variability shared between carbamazepine therapy, age of the subjects, and steroid levels and correlating with the variables as follows pregnenolone sulphate (PregS)-FP: R= -0.844, p<0.01; DHEAS-FP: R= -0.923, p<0.01; PregS-LP: R= -0.876, p<0.01; DHEAS-LP: R= -0.902, p<0.01; carbamazepine therapy: R=0.441, p<0.01; age of the participants (R=0.584, p<0.01). Carbamazepine significantly decreased DHEAS in both FP (p=0.02) and LP (p=0.003) and PregS in LP (p=0.03) and tended to decrease the PregS levels in FP (p=0.10), while primidone decreased DHEAS in both FP and LP (both p=0.05) and did not significantly change the levels of PregS. In conclusion, carbamazepine and primidone therapies significantly suppressed the sulphated steroids in serum.

[Progesterone neuroactive metabolites in human pregnancy]. / Progesteron a jeho neuroaktivní metabolity v mechanismu porodu.

OBJECTIVE: Review of the physiological role of neuroactive and neuroprotective steroids in human pregnancy. DESIGN: A review article. SETTING: Gynecological-Obstetrical Clinic, 1st Medical Faculty, Charles University and General Hospital, Prague. CONCLUSION: Human parturition is a multi-factorial process. Various mechanisms related to the onset of labor were suggested. Estrogens show accelerating increase in late pregnancy, which probably reflect the increasing activity of fetal zone of the fetal adrenal. This zone is stimulated by progressive increase of placental CRH resulting in excessive production of conjugated 3beta-hydroxy-5-en-steroids, which are transported by circulation to placenta and further metabolized to active hormones. Some progesterone metabolites probably participate in pregnancy sustaining via modulation of ligand-gated ion channels in the CNS and periphery. In this review, the question was addressed whether the catabolism of pregnancy sustaining progesterone metabolites accelerate like the estrogen formation.

Melatonin negatively correlates with C-peptide after food intake.

Melatonin plays a key role in the circadian timing system. At present, many other functions of melatonin are known. Question remains whether changes in endogenous melatonin may be associated with food intake. Hence, the levels of melatonin, C-peptide and glucose were followed during a daily regimen (16 hours) including standardized food intake using commercial kits. The diurnal profiles of the hormones and serum glucose were evaluated using ANOVA with Period and Subject as independent factors. Pearson's correlations and using a multiple stepwise backward regression model consisting of the time factor as a polynomial, and serum C-peptide and glucose assessed the correlations between melatonin and the remaining parameters. Our results showed a significant negative correlation between melatonin and C-peptide. The profile of melatonin was physiological, decreasing after wake-up, showing minor changes during the daytime and increasing in the evening. As documented, lesser alterations were indicated in the course of the melatonin daytime profile, which may reflect periodic food intake. Food intake is not the primary factor influencing the melatonin course. While previous studies have mostly considered the protective effect of melatonin in diabetic subjects, our study brought the results suggesting food intake as a factor contributing to daytime melatonin variation in humans. However, the physiological role of melatonin association with food intake in daytime remains in question and should be further investigated.

Increase of nocturnal melatonin levels in hemodialyzed patients after parathyroidectomy: a pilot study.

In hemodialyzed patients hormonal disturbances are known to occur. However, melatonin levels have not been completely studied. The aim of the study was to find whether changes in calcaemia affect melatonin secretion. For this reason we followed the nocturnal serum concentrations of melatonin and parathyroid hormone (PTH) in 9 hemodialyzed patients (6 women and 3 men, aged 37-65 years) both before and 1-3 months after parathyroidectomy at 6 p.m., 9 p.m., 11 p.m., 2 a.m., 5 a.m. and 7 a.m. At 6 p.m. blood samples to evaluate the levels of calcium and phosphate were also collected. Parathyroidectomy resulted in an increase in nocturnal melatonin levels. As expected, the parathyroidectomy was followed by considerable PTH decrease. PTH showed no nocturnal variation before or after parathyroidectomy. Calcium levels significantly decreased after the operation while phosphate levels increased. In summary, in hemodialyzed patients with hyperparathyroidism, parathyroidectomy significantly increases the nocturnal secretion of melatonin. Relationships between the pineal gland and parathyroid glands have yet to be elucidated.

Pregnanolone isomers, pregnenolone and their polar conjugates around parturition.

The levels of four pregnanolone isomers and their polar conjugates and pregnenolone sulfate were measured in the plasma of 13 and 7 women at delivery with subarachnoidal and epidural analgesia, respectively, and in corresponding samples of umbilical plasma using a simple quadrupole GC/MS system with electron impact ionization (pregnenolone isomers), RIA following HPLC separation (pregnenolone) and specific RIA (pregnanolone sulfate). The concentration of epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one) in both maternal and umbilical plasma was much lower than that of other pregnanolone isomers. The levels of 3beta-hydroxy-pregnanolone isomers were significantly higher in the umbilical plasma than in the maternal, while the differences in 3alpha-hydroxy-isomers were insignificant. The differences in conjugates were insignificant with the exception of allopregnanolone, the levels of which were lower in umbilical plasma. In all the pregnanolone isomers, a significantly lower conjugated/unconjugated steroid ratio was found in the umbilical plasma than in the maternal plasma. In addition, time profiles of the steroids were measured around parturition and in the postpartum period in the maternal serum. Similarly, the levels of polar conjugates of all pregnanolone isomers were followed during parturition. Changes in concentrations of free steroids exhibited a similar pattern, with a fall primarily within the first hour after delivery. The decrease in conjugated steroids was shifted to the interval within the first hour and first day after delivery, and the changes were more pronounced. The time profiles of the conjugated/free steroid ratio exhibited a significant decrease within the first hour and the first day after delivery in all of the isomers investigated. A decrease was also observed in the ratio of 3alpha/3beta-isomers and 5alpha/5beta-isomers around parturition. The possible physiological consequences of the findings are indicated.

Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal and umbilical blood: 3.3beta-hydroxy-5-ene steroids.

Five 3beta-hydroxy-5-ene steroids involved in the metabolic route from pregnenolone sulfate to dehydroepiandrosterone and its sulfate, of which three are known allosteric modulators of neurotransmitter receptors, were monitored in the serum of 20 women around parturition. In addition, their levels in maternal and umbilical serum were compared at delivery. On the basis of these data, a scheme of steroid biosynthesis in maternal organism during the critical stages around parturition is proposed. In maternal serum, all the steroids except dehydroepiandrosterone sulfate decreased during labor and even first day after delivery, although their changes were less distinct the more distant from pregnenolone sulfate (PregS) in the metabolic pathway. Calculation of product/immediate precursor ratios in maternal serum over all stages around parturition enabled identification of the respective changes in the activities of the relevant enzymes. The ratio of 17-hydroxypregnenolone/pregnenolone did not change significantly, while that of dehydroepiandrosterone/17-hydroxypregnenolone grew, indicating increased C17,20 side chain cleavage on the account of C17-hydroxylation both catalyzed by C17-hydroxylase-C17,20-lyase. As was shown by factor analysis, the changes in the maternal steroids were associated with a single common factor, which strongly correlated with all the steroids except dehydroepiandrosterone sulfate. The lack of change in the pregnenolone sulfate/pregnenolone ratio and a marked increase of the ratio dehydroepiandrosterone sulfate to unconjugated dehydroepiandrosterone indicate a different means of formation of both steroid sulfates. On the basis of these data, a scheme of steroid biosynthesis in maternal organism during the critical stages around parturition is proposed.

Lack of melatonin response to acute administration of nifedipine and diltiazem in healthy men.

Calcium antagonists have been shown to influence some endocrinological processes in mammals. The use of calcium channel blockers in clinical practice is well documented. The current study monitored nocturnal melatonin, prolactin, and cortisol levels in 19 healthy volunteers before and after administration of calcium channel blockers. The effect of nifedipine was tested in 9 subjects, while diltiazem was administered in 10 men. The nocturnal profile of the given parameters was studied between 23:00 and 05:00 h. At midnight (zero time), the participants were given placebo, nifedipine (in a sublingual dose of 20 mg) or diltiazem (in a single dose of 90 mg). The hypothesis that calcium channel blockers decrease nocturnal melatonin secretion has not been confirmed. The mean nocturnal levels of melatonin between 01:00 and 05:00 h were: 78.1+/-8.8 (control study) vs. 82.4+/-10.2 ng/l (nifedipine study) and 73.0+/-5.3 ng/l (control study) vs. 75.1+/-5.1 ng/l (diltiazem study). In conclusion, the calcium channel blockers used in this study do not alter the nocturnal melatonin secretory process in healthy men.

Circulating beta(2) microglobulin in relation to bone metabolism: implications for bone loss with aging.

The aim of this cross-sectional study was to evaluate the relationships between circulating beta(2) microglobulin (beta(2) m) and bone mineral density (BMD), parameters of bone remodeling, vitamin D metabolites, parathyroid hormone (PTH), estradiol levels, and age in a group of 165 clinically healthy or osteoporotic, but otherwise normal untreated women. In this group of women, systemic beta(2) m correlated with BMD (g/cm(2)) levels for total hip and Ward's triangle (r = -0.298, P < 0.0001; and r = -0.299, P < 0.0001, respectively), but only at the borderline level with BMD at the spine (r = -0.145, P = 0.0604). Serum beta(2) microglobulin markedly correlated with age (r = 0.512, P = 0.0001). beta(2) m levels correlated with indices of bone remodeling, as well as with serum creatinine and estradiol levels. However, after stratification of all analyses by age, body mass index, and serum 25OHD(3), 1, 25(OH)(2)D(3), PTH, or estradiol levels (using standard multiple regression and stepwise forward regression models), only 25OHD(3) was found to be an independent predictor of BMD at the hip, including Ward's triangle, as estradiol of BMD at the spine. On the other hand, beta(2) m was not associated with BMD at any of the measured regions. Also, no association was found between serum PTH and BMD values. Therefore, systemic beta(2) m seems to be an indicator of bone remodeling in the course of natural skeletal aging rather than a variable independently predicting bone loss.

Effect of 1,25(OH)2 vitamin D3 on circulating insulin-like growth factor-I and beta 2 microglobulin in patients with osteoporosis.

To test the hypothesis that growth factors mediate the stimulatory effect of 1,25(OH)2 vitamin D3 [1,25(OH)2D3] on bone remodeling in osteoporosis, the authors studied the effect of the secosteroid administration in two doses (1 microgram/day and 2 micrograms/day) for 14 days on circulating insulin-like growth factor-I (IGF-I), beta 2 microglobulin, and osteocalcin in 18 osteoporotic women. The biological effectiveness of the treatment was controlled by a decline of serum intact parathyroid hormone. Compared with the values before treatment, 1,25(OH)2D3 increased means of plasma IGF-I, beta 2 microglobulin, and serum osteocalcin significantly; however, the effects were only apparent after the higher dose of the drug (169 +/- 26 versus 134 +/- 28 ng/ml, P < 0.01; 2.08 +/- 0.1 versus 1.92 +/- 0.1 micrograms/ml, P < 0.05; and 8.5 +/- 1.3 versus 5.4 +/- 1.1 ng/ml, P < 0.01, respectively). The authors conclude that exogenous 1,25(OH)2D3 promotes the production of IGF-I and beta 2 microglobulin in osteoporotic patients in parallel to the marker of osteoblastic function, osteocalcin, which supports the tested hypothesis.

The effect of 1,25(OH)2 vitamin D3 on CD4+/CD8+ subsets of T lymphocytes in postmenopausal women.

The effect of exogenous 1,25(OH)2 vitamin D3 (1,25(OH)2D3) on the CD3+, CD4+ and CD8+ subsets (counts/ul) of T lymphocytes was investigated in two randomized groups of postmenopausal women. Group one (16 subjects) received 1 ug/day of the secosteroid for 14 days, while group two (14 participants) was treated with 2 ug/day for the same period. The placebo group comprised another 10 postmenopausal women. Compliance of the treatment was controlled by serum intact parathyroid hormone (PTH) levels, which markedly declined at the end of the treatment (p<0.01 for both doses). The vitamin D status of the women before the treatment was defined by serum 25(OH) vitamin D (25(OH)D) levels. The lower dose of the secosteroid did not change any of the measured immune parameters. After a higher dose of 1,25(OH)2D3 the mean values of CD3+ and CD8+ increased (p<0.05 for the both parameters), but no changes in total lymphocytes and the CD4+ subset were observed. There were no correlations between the immune response (delta CD3+, delta CD4+ and delta CD8+) and basal circulating 25(OH)D. Briefly, then, 1,25(OH)2D3 slightly but significantly increases CD3+ and CD8+ subsets independently on the initial vitamin D status of the postmenopausal women.

Effect of estrogen status on bone regulating hormones.

The effect of surgically induced menopause and a subsequent estrogen monotherapy on the secretion of calciotropic hormones and serum minerals was evaluated in 11 perimenopausal menstruating women. In seven of them, plasma insulin growth factor-I was also assessed. In the 12th-16th week after bilateral oophorectomy, a decline of serum PTH (p < 0.01) and an increase of calcemia (p < 0.05), phosphatemia (p < 0.05), and IGF-I (p < 0.01) were documented. A subsequent transdermal estrogen substitution (100 micrograms/day for 6 weeks) returned these values to the preoperative range. However, neither the operation nor the estrogen treatment altered calcitonin secretion (basal and calcium stimulated), serum 1,25(OH)2, vitamin D3, or magnesium. The effectiveness of oophorectomy as well as compliance of estrogen substitution was documented by serum estradiol, FSH, and LH response. The results demonstrate a stimulating effect of estrogen on PTH secretion, secondary to an estrogen-induced reduction in plasma calcium. They further demonstrate an inhibitory effect on phosphatemia and IGF-I production, but no effect on calcitonin secretion and vitamin D metabolism.

[Melatonin--the hormone of darkness]. / Melatonin--hormon tmy.

Melatonin is a hormone produced mainly by the pineal gland during the dark phase of the circadian cycle with typical circadian rhythm with maximal secretion at night and depression during the day. The indoleamine has wide regulatory and integrative functions. Perhaps there is no organ and system which can escape the influence of epiphysis, incl. reproductive, cardiovascular gastrointestinal, respiratory as well as renal system and water and mineral metabolism. Melatonin regulates not only neuroendocrine functions but also has immunoenhancing and antitumor effects. That is why there are trials/attempts these properties to be utilized in the treatment of malignancies and AIDS patients. The hormone plays a certain role in temperature regulation in mammals as well as in the onset of puberty and senescence. Attention has been paid to its role as a scavenger of toxic free radicals and it is believed that melatonin is the most effective lipophilic antioxidant. However, the exact mechanism of action of this high active hormone remains to be elucidated. Further studies are also necessary for discovering the next its properties and functions.

Effect of surgically induced hypoestrinism on immunoregulation in perimenopausal women.

The object of the present study was to investigate the effect of bilateral oophorectomy (OOX) on CD4+ and CD8+ subsets of T-lymphocytes in 8 immunologically healthy perimenopausal women with regular bleeding. Between the 12th and 16th week after OOX, CD8+ (%) increased in all of the investigated women (mean values compared to values before OOX: 37.8 +/- 3.4 vs 26 +/- 4.13, p < 0.05). CD4+ increased in five women, and decreased in another three (means: 36.4 +/- 3.6 vs 38 +/- 4.6). The immunoregulatory index (CD4+/CD8+ ratio) declined in seven women, while it was unchanged in one (means: 1.09 +/- 0.2 vs 1.71 +/- 0.22, p < 0.05). The compliance of the treatment was controlled by serum estrogen, LH and FSH. From these results it is apparent that surgically induced hypoestrinism inhibits immunoregulation in perimenopausal women.

Adenohypophyseal-gonadal dysfunction in male haemodialyzed patients before and after subtotal parathyroidectomy.

The function of the adenohypophyseal-gonadal axis in haemodialyzed male patients is modified: the serum testosterone level is low, and the gonadotropin levels are increased. The pathogenetic role of secondary hyperparathyroidism in this disorder has not previously been defined. The area under the curve (AUC) and the secretion kinetics of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone after administration of LH-releasing hormone were examined in 7 dialyzed men with secondary hyperparathyroidism (mean age 36.2, range 20-47 years) before and 3 and 6 months after parathyroidectomy (PTX). The operation was successful in all 7 patients, as intact parathyroid hormone declined markedly during both postoperative periods as compared with the values before PTX: 81 +/- (SEM) 34 and 138 +/- 57 ng/1 versus 965 +/- 116 ng/l (p < 0.01 and p < 0.0l). The testosterone AUC prior to PTX (63 +/- 115 nmol/l x min) and 3 months (-4 +/- 36 nmol/l x min) and 6 months after PTX (-62 +/- 69) did not differ significantly, as was the case with LH AUC (1,110 +/- 223 and 1,214 +/- 331 and 1,020 +/- 314 U/l x min, respectively) and follicle-stimulating hormone AUC (525 +/- 334 and 634 +/- 347 and 533 +/- 264 U/l x min, respectively). The secretion kinetics of all three hormones was atypical as compared with healthy men of similar age, but it did not change after PTX. There were no correlations between the sexual indicators and parathyroid hormone, 1,25(OH)2D3, calcium, or phosphate during the individual periods. These findings indicate that secondary hyperparathyroidism is probably not involved in the dysfunction of the adenohypophyseal-gonadal axis in dialyzed men.