The CSF and arterial to internal jugular venous hormonal differences during exercise in humans.

Strenuous exercise increases the cerebral uptake of carbohydrate out of proportion to that of oxygen, but it is unknown whether such enhanced carbohydrate uptake is influenced by the marked endocrine response to exercise. During exhaustive exercise this study evaluated the a-v differences across the brain (a-v diff) of hormones that could influence its carbohydrate uptake (n= 9). In addition, neuroendocrine activity and a potential uptake of hormones via the cerebrospinal fluid (CSF) were assessed by lumbar puncture postexercise and at rest (n= 6). Exercise increased the arterial concentration of noradrenaline and adrenaline, but there was no cerebral uptake. However, following exercise CSF noradrenaline was 1.4 (0.73-5.5) nmol l(-1), and higher than at rest, 0.3 (0.19-1.84) nmol l(-1) (P < 0.05), whereas adrenaline could not be detected. Exercise increased both the arterial concentration of NH(4)(+) and its a-v diff, which increased from 1 (-12 to 5) to 17 (5-41) micromol l(-1) (P < 0.05), while the CSF NH(4)(+) was reduced to 7 (0-10) versus 11 (7-16) micromol l(-1) (P < 0.05). There was no release from, or accumulation in the brain of interleukin (IL)-6, tumour necrosis factor (TNF-alpha), heatshock protein (HSP72), insulin, or insulin-like growth factor (IGF)-I. The findings indicate that for maximal exercise, the concentration of noradrenaline is increased within the brain, whereas blood borne hormones and cytokines are seemingly unimportant. The results support the notion that the exercise-induced changes in brain metabolism are controlled by factors intrinsic to the brain.

Changes with aging of steroidal levels in the cerebrospinal fluid of women.

OBJECTIVE: Age-related changes of steroid levels in the central nervous system (CNS) are not well understood. To investigate whether steroidal conditions in the CNS of women change with aging and menopause, steroid levels have been measured in serum and cerebrospinal fluid (CSF), and examined correlations with aging. METHODS: Serum and CSF concentrations of estradiol (E2), cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS) and albumin were measured in 80 female patients who underwent operations for benign gynecological diseases. They had no endocrinological or neurological disorders and were aged 17-71 years; 62 patients were in premenopause and 18 were in postmenopause. RESULTS: Serum levels of E2 decreased markedly after menopause, while levels of DHEA and DHEAS decreased gradually with age. There was no significant change with age of serum cortisol levels. The CSF concentrations of E2 (0.2-3 pg/ml) decreased with age [correlation coefficient (r)= 0.31, P < 0.01]. The CSF DHEA levels (0.1-0.8 ng/ml) did not change with age although not significantly, but CSF cortisol levels (0.1-0.6 microg/dl) increased with age (r = 0.35, P < 0.01). The CSF DHEAS concentrations were below the sensitivity of the radioimmunoassay (RIA) (1 ng/ml). The CSF/serum ratios of cortisol increased with age (r = 0.30, P < 0.01), as did those of DHEA (r = 0.55, P < 0.01). Although serum albumin levels did not change throughout life, CSF albumin levels and CSF/serum albumin ratios increased gradually with age (r = 0.28, P = 0.052; r = 0.23, P = 0.114, respectively), but there was no significance. There were marked decreases of serum E2 and DHEA levels and CSF E2 levels in postmenopausal women (P < 0.05), but CSF cortisol levels increased (P < 0.05) and DHEA levels in CSF were maintained after menopause. CONCLUSION: These results indicate that steroids in CSF become cortisol dominated and deficient in estrogens with aging, especially after menopause.

CSF and endocrine studies of premenstrual syndrome.

Eight women with prospectively documented premenstrual syndrome (PMS) underwent multiple samplings for estradiol, progesterone, prolactin, cortisol, and plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) during an asymptomatic midcycle (late follicular) and a symptomatic premenstrual (late luteal) phase of the menstrual cycle. Cerebrospinal fluid (CSF) was collected for analysis of MHPG, norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC), gamma-aminobutyric acid (GABA), homovanillic acid (HVA), tyrosine, tryptophan, beta-endorphin, prostaglandins, adrenocorticotropic hormone (ACTH), and arginine vasopressin (AVP). In subsequent months, a dexamethasone suppression test (DST) and a thyrotropin-releasing hormone (TRH) stimulation test were performed during midcycle and premenstrual phases. Significant results included increased CSF concentrations of MHPG in the premenstrual, as compared with the midcycle, phase of the cycle, and increased plasma cortisol concentrations during the midcycle phase. The DST showed a 62% overall rate of nonsuppression, irrespective of menstrual cycle phase. Though there were no abnormalities of thyrotropin-stimulating hormone (TSH) after TRH stimulation, the mean delta maximum prolactin values after TRH stimulation were higher than reported normal values both at midcycle and premenstrually. These pilot data suggest hormonal axes that might be worthy of further systematic investigation in future studies of PMS.

Cerebrospinal fluid estrone in pseudotumor cerebri: a change in cerebral steroid hormone metabolism?

Estrogen and androgen hormones were studied in the plasma and cerebrospinal fluid (CSF) of five patients affected by pseudotumor cerebri (PTC). Six men and six women without cerebral or endocrine diseases were selected as controls. Androstenedione (A), testosterone (T), 17-hydroxyprogesterone (17OH-P), E1 and E2 were measured in plasma and CSF in baseline conditions and following 1 month prednisone therapy (2 mg/die, per os) using RIA following chromatographic separation on celite microcolumns. Men and women affected by PTC show increased CSF E1 levels and marked decreased CSF A levels, with respect to controls. In plasma, on the contrary, normal values of these parameters were observed in PTC. In normal subjects A/E1 ratio shows the same values in plasma and CSF, suggesting for the two hormones analogous feasibility to cross the blood brain barrier. In PTC patients A/E1 ratio is comparable to controls in plasma, but lower in CSF as a result of decreased A and increased E1 contents. The CSF imbalance between A and E1 attenuates but does not disappear after treatment. No correlation is found between pressure levels and steroid pattern both in baseline condition or after one month of treatment. In conclusion, our results demonstrate that PTC is not only associated with increased CSF E1 levels, as previously suggested, but, above all, with decreased CSF A levels and this hormonal impairement seems to be confined to the CSF compartment and not observed in plasma. These data do not lead to any definitive conclusion about the role of altered CSF estrogen and androgen levels in PTC pathogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonal changes in cerebral infarction in the young and elderly.

Fifty-one patients with CCT verified cerebral infarction were submitted to serum and CSF radioimmunoassay of FSH, LH, estradiol (E2), progesterone, testosterone, cortisol and T4. The results were compared to those of 82 matched controls. Our findings suggest that (1) high serum E2 is a risk factor of stroke in males; (2) low serum T4 is a risk factor in males; (3) serum testosterone is reduced in acute stroke in males confirming that it is stress sensitive; (4) serum LH was higher in hypertensive thrombotic males when compared to normotensive ones, and (5) FSH, LH, E2 and T4 are undetectable in CSF of patients and controls.

Physiological neuroendocrinology of peptides, steroids and other hormones in cerebrospinal fluid.

Cerebrospinal fluid acts as a conduit in neuroendocrine regulation. Valid assessment of normal cerebrospinal fluid levels of peptides, steroids and other hormones requires clarification of reference concentrations in control patients and normal volunteers. Awareness of factors which may alter neuronal activity and, in turn, the relative composition of cerebrospinal fluid constituents is essential to the accurate sampling and hormonal analysis of cerebrospinal fluid.

Neuroendocrinology of cerebrospinal fluid: peptides, steroids, and other hormones.

Cerebrospinal fluid (CSF) has been implicated as a conduit in neuroendocrine integration. Evidence suggests that the ventricular CSF may promote the central distribution, enable the dilutional inactivation (sink effect), and facilitate the peripheral delivery of neurally secreted hormones. This discussion of the sites of origin and concentration gradients of CSF hormones and of both physiological and pharmacological variations in the hormonal content of the CSF provides insight into the putative role of CSF in neuroendocrine regulation. Normal or control concentrations of peptides, steroids, and other hormones present in human lumbar CSF are listed to provide a physiological base line to which the CSF hormonal profile of patients may be compared. The individual, somatotopic, chronological, endocrinological, pharmacological, and possible artifactual variations in CSF hormonal composition are presented to facilitate the formulation of clinical protocols and to eliminate possible sources of error.