A biological characterization of patients with postmenopausal Parkinson's disease.

Menopause increases the risk for Parkinson's disease (PD), although the underlying biological mechanisms have not been established in patients. Here, we aimed to understand the basis of menopause-related vulnerability to PD. Main motor and non-motor scores, blood levels of estradiol, testosterone, follicle-stimulating hormone, and luteinizing hormone, CSF levels of total α-synuclein, amyloid-ß-42, amyloid-ß-40, total tau, and phosphorylated-181-tau were examined in 45 women with postmenopausal-onset PD and 40 age-matched controls. PD patients had higher testosterone and lower estradiol levels than controls, and the residual estradiol production was associated with milder motor disturbances and lower dopaminergic requirements. In PD but not in controls, follicle-stimulating hormone levels correlated with worse cognitive scores and CSF markers of amyloidopathy and neuronal loss. In conclusion, menopause-related hormonal changes might differentially contribute to clinical-pathological trajectories of PD, accounting for the peculiar vulnerability to the disease.

Mullerian-inhibiting substance in women with polycystic ovary syndrome: relationship with hormonal and metabolic characteristics.

The aim of the present study was to examine the relationship between Mullerian-inhibiting substance (MIS) levels and metabolic characteristics in women with polycystic ovary syndrome. Increased ovarian MIS production may exert a paracrine negative control on follicle growth sufficiently to prevent selection of a dominant follicle.

Cerebrospinal fluid and blood concentrations of luteinizing hormone, follicle stimulating hormone and prolactin following castration of adult male rats.

Comparative levels of LH, FSH, and PRL in the serum and cerebrospinal fluid (CSF) of adult male rats were studied at different periods following castration. Intact and sham-operated animals served as controls. Blood and CSF were collected at 1, 3, 7, 14, 21, 28, 35 and 46 days following castration. The CSF was collected via cisterna-magna puncture, while the blood was collected from abdominal aorta. Serum gonadotropins increased progressively beginning day 1 post-castration to reach maximum by day 35 or 46 post-castration. Sham operation and castration did not affect mean CSF, LH and FSH levels compared to intact controls. Analysis of the temporal pattern of serum and CSF gonadotropin levels following castration revealed significant positive correlation between CSF and serum LH (r = 0.58) and FSH (r = 0.64) levels respectively. The data suggest that CSF gonadotropins may be derived from systemic circulation. Serum PRL levels were not affected by castration, but CSF PRL levels were significantly reduced at days 28, 35 and 46 post-castration compared to intact controls. CSF PRL levels showed negative correlation with serum LH and FSH levels but failed to show a correlation with serum PRL levels. Hypothalamic norepinephrine turnover rate increased at days 28, 35 and 46 post-castration. Hypothalamic dopamine contents and turnover rates were reduced at days 21 and 28 post-castration. It is suggested that CSF PRL may have a role in the regulation of serum gonadotropins.

Dopamine in the cerebrospinal fluid of prepubertal and adult horses.

Catecholamine concentrations (pg/ml) in the cerebrospinal fluid (CSF) of prepubertal (n = 9) and adult (n = 18) horses were determined by radioenzymatic assay. Norepinephrine was low or non detectable in all CSF samples. In contrast, measurable CSF dopamine concentrations were effected by age, reproductive status and exogenous steroid treatments. The concentration of dopamine in the CSF of prepubertal females (733 +/- 92) was greater (p less than 0.05) than the concentration in the CSF of prepubertal males (117 +/- 67). Prepubertal male horses which were treated with testosterone for 5 days (50 mg/day) had elevated (p less than 0.05) dopamine concentrations (2,533 +/- 1,160) in the CSF compared to control males. In adult mares, dopamine was lower (p less than 0.05) in the ovulatory season (25 +/- 10) than during the anovulatory season (200 +/- 101). Daily intramuscular estradiol-17 beta (5 mg/day) injections had no effect (p less than 0.05) on dopamine concentrations in the CSF of seasonally anovulatory mares (250 +/- 35). Further, concentrations of dopamine in the CSF of long-term ovariectomized mares (80 +/- 21) were not influenced (p less than .05) by season. These results suggest that age, sex and gonadal steroids may effect dopamine, but not norepinephrine, concentrations in the brain ventricular system of the equine species. Further, seasonal effects on CSF dopamine concentrations are dependent upon the presence of the ovaries.

LH and FSH levels in serum and cerebrospinal fluid (CSF) of human fetus.

The concentration of LH and FSH was measured in the fetal blood and cerebrospinal fluid (CSF) of 4 human fetuses between 21 and 24 weeks old. A comparison was made with 6 post menopausal females. In one fetus the serum and CSF levels of both hormones were determined after administration of 200 micrograms LRH and 400 micrograms TRH. The mean serum fetal levels of LH and FSH of 76.6 mIU/ml (range, 29.5-152.0) and 30.5 mIU/ml (range 3.1-60.3), respectively, were not significantly different from those of postmenopausal females, whereas the fetal CSF levels of these hormones were significantly higher (p less than 0.02) than those of post menopausal females. The serum to CSF ratios for the fetal LH and FSH were 4.6 +/- 1.1 and 2.4 +/- 0.61 respectively, significantly different (p less than 0.02 and p less than 0.001 respectively) from those of post menopausal females (29.1 +/- 6.6 for LH and 50.9 +/- 10.9 for FSH). In one fetus LRH did not provoke any change in circulating FSH and LH level 20 min. after administration, while a slight increase of these hormone in the CSF was observed. These data suggest that the permeability of blood-CSF barrier to gonadotropins in the fetus seems to be higher than in the adult who has no blood-CSF barrier (B--CSF--B) alterations.

LH and FSH in human cerebrospinal fluid.

LH and FSH of cerebrospinal fluid (CSF) and serum were radioimmunologically measured. Samples were obtained simultaneously from 116 subjects of the following groups: A. 22 patients with non-endocrine diseases, B. 18 patients with cranial diabetes insipidus (DI) of whom 4 with metastatic carcinomas, C. 5 patients with primary empty sella syndrome, D. one with hydatiform mole, and E. 70 patients with pituitary adenomas, i.e. growth hormone--or prolactin-secreting or "non-secreting" adenomas, of whom 38 patients with invasive and 32 with enclosed adenomas. LH and FSH are normal constituents of CSF and their CSF levels poorly correlates with the serum ones (LH r = 0.477 p less than 0.01). Enclosed adenomas with SSE showed low levels of LH in CSF. High CSF-gonadotropins concentrations (above 4.0 mIU/ml) with a low serum/CSF ratio (below 3) was frequently, but not constantly found in patients with invasive adenomas and are not indicative per se of this diagnosis. Some patients with brain metastasis from breast carcinoma and DI, or with non-tumoral diseases and DI showed similar high patterns of CSF gonadotropins though the serum levels were within normal range. This suggests that local vascular mechanisms, including the retrograde circulation of gonadotropins from the pituitary to the hypothalamus, influence the blood-brain barrier much more than the release of gonadotropins into the systemic blood circulation.

Adenohypophyseal hormone levels in the cerebrospinal fluid of patients with pituitary disease.

Measurement of adenohypophyseal hormones in the cerebrospinal fluid (CSF) was recently proposed as an useful procedure to differentiate pituitary intra and extrasellar tumors. So far, data reported are conflicting. We measured the concentrations of GH, TSH, LH and PRL in CSF and plasma in 30 controls and in 37 patients with various pituitary diseases (18 intrasellar adenomas, 14 extrasellar adenomas and 5 empty sella syndromes). The concentrations of examined hormones in CSF were very low or undetectable in all control subjects. In most patients with pituitary tumors, adenohypophyseal hormones were found to be present in CSF, in great amounts. No significant differences were found between intra and extrasellar tumors. In agreement with recently reported data, no significant correlation was found between GH, TSH, FSH and LH levels in CSF and plasma, while a significant correlation (p less than 0.01) was obtained between CSF and plasma levels of PRL, either in all patients or in those with extrasellar tumors only. All patients bearing an empty sella had PRL detectable in CSF: in 2 cases PRL levels were very high. In conclusion our data do not confirm that measurement of adenohypophyseal hormones in CSF represents an useful screening to differentiate tumors with extrasellar extension. PRL data deserve interest in order to gain understanding of the hormone dynamics between CSF and vascular compartments.

Adenohypophyseal hormones in the CSF.

The presence of adenohypophyseal hormones in human cerebrospinal fluid (CSF) had been firmly established by radioimmunoassay procedures. The hormones can originate from the adenohypophysis itself and from brain, as well as from peripheral sites of production. These peptide hormones enter the CSF through the choroid plexus or by direct secretion. The hormones entering by direct secretion into the CSF have a higher CSF-blood ratio than the hormones entering through the choroid plexus. Elevated CSF levels of adenohypophyseal hormones are most likely to occur in the presence of hormone-producing pituitary tumors with suprasellar extension. Although the CSF concentrations of adenohypophyseal hormones may merely reflect their blood concentrations, it is more likely that these hormones also have paracrine as well as endocrine effects.

Anterior pituitary hormone levels in the cerebrospinal fluid of patients with pituitary and parasellar tumors.

Cerebrospinal fluid (CSF) concentrations of growth hormone, prolactin (PRL), adrenocorticotropin, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, and the glycoprotein hormone alpha subunit were determined in 30 patients with pituitary and parasellar tumors. Although many of the patients had elevated hormone levels, no differentiation between patients with intrasellar tumors and those with pituitary tumors with suprasellar extension or primary suprasellar tumors could be made based upon the absolute CSF hormone concentration. A highly significant correlation between serum and CSF PRL concentrations was found (r = 0.87; P less than 0.001), suggesting that CSF PRL is derived from the serum. No correlation was found between the serum and CSF concentrations of the other anterior pituitary hormones.

Suprasellar extension of tumour associated with increased cerebrospinal fluid activity of LH and FSH.

A 65 year old man with pituitary adenoma, partial hypopituitarism and normal serum FSH and LH concentration is described. LH (but not FSH) partially increased following the administration of LH-RH. Subsequent FSH and LH assays of the cerebrospinal fluid, however, showed a high and correctly predicted suprasellar extension of the tumour.

Effect of chlorpromazine treatment on prolactin levels in cerebrospinal fluid and plasma of psychotic patients.

In psychotic patients, levels of prolactin in cerebrospinal fluid (CSF) and plasma were determined by radioimmunoassay before and after 2 and 4 weeks of treatment with chlorpromazine (CPZ). CPZ was given in one of three randomly selected fixed doses: 200, 400 or 600 mg per day. Before treatment, low levels of immunoreactive prolactin-like material (PRL) were found in the CSF of most patients. The concentration in CSF was about 20% of the plasma level. In CSF but not in plasma, the pre-treatment level of PRL was significantly higher in women than in men. During CPZ treatment, the PRL levels in CSF as well as in plasma were significantly elevated in both sexes after 2 as well as 4 weeks. The elevation was significantly greater in women, and was similar at the two time intervals studied. There was a significantly positive relationship between the dose of CPZ and the PRL elevation in both body fluids in both men and women. Before treatment no significant correlation between the PRL levels in CSF and plasma in either sex could be observed. During treatment, there was a significant correlation between the change in PRL levels in CSF and plasma in both men and women. CPZ treatment did not increase the levels of total protein, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH) or oestradiol-(17-beta) in either the CSF or the plasma.

Cerebrospinal fluid hormone concentration in the evaluation of pituitary tumors.

Cerebrospinal fluid (CSF) concentrations of corticotropin, growth hormone, thyrotropin, prolactin, luteinizing hormone, and follicle stimulating hormone were measured in 28 patients with various neurologic disorders, in 49 patients with pituitary tumors of whom 22 had suprasellar extension, and in 6 patients with craniopharyngiomas. With the exception of 1 patient with pseudotumor cerebri, CSF adenohypophyseal hormone concentrations were low in patients with neurologic disease and in patients with pituitary tumor without suprasellar extension. In marked contrast, 21 to 22 patients with suprasellar extension of a pituitary tumor and 2 of 6 patients with a craniopharyngioma had elevations of one or more CSF adenohypophyseal hormones. Posttreatment CSF adenohypophyseal hormone levels fell from previously elevated levels in 4 of 5 patients. These data suggest that an elevated CSF adenohypophyseal hormone concentration is a sensitive indicator of suprasellar extension of a pituitary tumor, and posttreatment measurements are useful in determining efficacy of therapy.