Leptin concentration in plasma and in milk during the interpartum period in the mare

The aim of this work is to investigate on plasma profiles of leptin and estradiol 17beta during the interpartum period and leptin concentrations in the milk and in the colostrum during the period from parturition to the successive delivery in mare. Leptin plasma concentration varied from 5.1+/-2.3 ng/ml after the first parturition (week 0) to 3.0+/-0.7 at week 21 (p<0.05), then it increased to maximal level at week 49 (6.9+/-1.0 ng/ml, p<0.05). Leptin concentration in the colostrum and in the milk has been significantly (p<0.05) higher than that in plasma samples at week 1 (milk 8.8+/-2.3 versus plasma 5.2+/-0.6 ng/ml) and between week 12 and 17. This difference may be explained with a local leptin production at mammary level and supports a role of leptin in the mammary gland and/or in foal intestine. Estradiol 17beta increased from week 15 (17.9+/-2.3 pg/ml) up to 487.9+/-67.7 pg/ml at week 43. Plasma estradiol 17beta rise anticipated by 4 weeks plasma leptin increase and it does not seem to be positively correlated to leptin secretion.     

Ghrelin is present in human colostrum, transitional and mature milk

Ghrelin and its mRNA have recently been found in numerous human tissues including breast. The aim of this study was to compare the ghrelin levels in colostrum, mature and transitional milk and plasma in lactating women with plasma samples from non-lactating women. Venous blood samples were obtained from 17 healthy lactating women aged 22-35 years and from 16 age-matched controls. Colostrum, transitional and mature milk samples were collected just before suckling. The level of bioactive ghrelin was determined by RIA. Comparison of ghrelin values for lactating women showed significantly lower concentrations in colostrum (70.3 +/- 18 pg/ml), transitional milk (83.8 +/- 18pg/ml) and mature milk (97.3 +/- 13 pg/ml) than in the corresponding plasma samples (first day 95 +/- 16 pg/ml, 10th day 111 +/- 13 pg/ml and 15th day 135 +/- 16 pg/ml). The plasma concentrations were lower in the lactating than in the non-lactating women. Thus, the ghrelin levels in colostrum, transitional and mature milk were elavated concomitantly with increasing plasma ghrelin after delivery. The origin of milk ghrelin is not known, but it probably comes from the plasma.     

High concentrations of procalcitonin but not mature calcitonin in normal human milk.

Procalcitonin (PCT) is one of the precursors in the synthesis of calcitonin in thyroidal C-cells and other neuroendocrine cells. PCT and other calcitonin precursors in serum are present at less than 50 pg/ml in healthy individuals, but are highly elevated in serum where conditions leading to systemic inflammatory response syndrome or sepsis prevail. We measured PCT concentrations in milk and serum samples taken from 9 healthy women after delivery. PCT concentrations were below 10 pg/ml in serum samples, but were more than 100 times as high in the corresponding milk samples. PCT in milk reached a maximum within the early days after delivery, with a median peak concentration of 2310 pg/ml (range 223 - 4224 pg/ml) at day one and 2442 pg/ml (range 952 - 4488 pg/ml) at day two, then declining over the next days to a median concentration of 747 pg/ml (range 443 - 1656 pg/ml) at day 10 (p = 0.012, by Friedman ANOVA). PCT values reached a steady state of 504 pg/ml median value. Mature calcitonin values measured in parallel with a specific assay were not above the normal range of 10 pg/ml in any samples measured. The strong discrepancy between serum and milk PCT suggests that PCT (but not mature calcitonin) is synthesised in the breast of healthy mothers after delivery. The precise mechanism and the physiological relevance are unclear. Since PCT levels increase drastically in serum from patients suffering from sepsis and related conditions, and since PCT has been ascribed a pro-inflammatory function, we propose that milk PCT might contribute to the activation of the developing neonatal immune system. Similar speculations were proposed for a variety of other pro-inflammatory cytokines, which had comparable kinetics in human milk.     

Increased plasma macrophage inflammatory protein (MIP)-1alpha and MIP-1beta levels in type 1 Gaucher disease

Pancytopenia, hepatosplenomegaly and skeletal complications are hallmarks of Gaucher disease. Monitoring of the outcome of therapy on skeletal status of Gaucher patients is problematic since currently available imaging techniques are expensive and not widely accessible. The availability of a blood test that relates to skeletal manifestations would be very valuable. We here report that macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, both implicated in skeletal complications in multiple myeloma (MM), are significantly elevated in plasma of Gaucher patients. Plasma MIP-1alpha of patients (median 78 pg/ml, range 21-550 pg/ml, n=48) is elevated (normal median 9 pg/ml, range 0-208 pg/ml, n=39). Plasma MIP-1beta of patients (median 201 pg/ml, range 59-647 pg/ml, n=49) is even more pronouncedly increased (normal median 17 pg/ml, range 1-41 pg/ml, n=39; one outlier: 122 pg/ml). The increase in plasma MIP-1beta levels of Gaucher patients is associated with skeletal disease. The plasma levels of both chemokines decrease upon effective therapy. Lack of reduction of plasma MIP-1beta below 85 pg/ml during 5 years of therapy was observed in patients with ongoing skeletal disease. In conclusion, MIP-1alpha and MIP-1beta are elevated in plasma of Gaucher patients and remaining high levels of MIP-1beta during therapy seem associated with ongoing skeletal disease.     

Identification and characterization of cyclo(His-Pro)-like immunoreactivity in amniotic fluid

Amniotic fluid (AF) from 25 term pregnancies was analyzed for cyclo(His-Pro)-like immunoreactivity (CHP-LI). CHP-LI was detected in all AF samples and was indistinguishable from synthetic CHP by immunoidentity, by gel chromatography on Sephadex G-25, and by high pressure liquid chromatography. The mean concentration of CHP-LI in AF was 13,622 +/- 1288 pg/ml (+/- SE) and concentrations were not altered by maternal labor. Plasma concentrations of CHP-LI were similar in 4 pregnant and 4 control subjects [2260 +/- 432 pg/ml vs. 2162 +/- 419 pg/ml (+/- SE), respectively]. We conclude that 1) CHP-LI is readily detected in AF from term pregnancies and is indistinguishable from synthetic CHP, and 2) concentrations of CHP-LI in human AF are significantly higher than concentrations of maternal plasma CHP-LI, suggesting CHP AF originates by mechanisms other than diffusion from maternal plasma.     

Gonadal steroid hormone level in blood plasma and milk of primiparous and multiparous nonpregnant and pregnant buffaloes

Changes in the concentration of progesterone and estradiol-17beta were measured by radioimmunoassay in 11 primiparous and 17 multiparous buffaloes at estrus and daily post insemination and in 6 nonbred buffaloes at 6 hour intervals from 4 days before expected estrus to one day after estrus. Plasma progesterone concentration at estrus was 0.1 ng/ml which rose to a peak level of 3.47 ng/ml on day 17. It fluctuated around this level in those animals which conceived, but followed a declining trend in those which failed to do so and attained lowest values on the day of next estrus. Temporal changes of the hormone revealed that the occurrence of major decline varjed between 16 and 62 h before estrus. The average concentration in milk was about three to four times higher than in plasma. The concentration of estradiol-17beta about 23.50 pg/ml at estrus and fluctuated around 10 pg/ml in animals that returned to estrus with a peak around estrus. Temporal changes of hormone revealed that peak level occurred 8-17 h before estrus. The concentration of estradiol in pregnant animals fluctuated around 10 pg/ml. The concentration in milk was about 2-3 times higher than in plasma. There was no significant (P > 0.05) difference in the concentrations of progesterone and estradiol-17beta between primiparous and multiparous animals.     

Immunoreactive and biologically active somatostatin in human and sheep milk

The presence of immunoreactive and biologically active somatostatin in sheep and human milk has been demonstrated. Milk somatostatin exhibits similar chromatographic behavior to that of synthetic somatostatin-14 on both reversed-phase C18 and cation-exchange high-performance liquid chromatography columns. Milk, in contrast to plasma, contains only somatostatin-14-like material. Milk somatostatin was capable of inhibiting the basal and the prostaglandin-induced release of growth hormone from anterior pituitary cell cultures in a pattern similar to synthetic somatostatin-14. The concentrations of the peptide, as determined by radioimmunoassay, were found to be 113 pg/ml in human milk and 150 +/- 4.8 pg/ml (mean +/- range) in sheep milk. These values are severalfold higher than the corresponding concentration of the peptide in the plasma of these species. These findings are analogous to our previous observations concerning two other hypothalamic hormones, luliberin and thyroliberin [Baram, T., Koch, Y., Hazum, E. and Fridkin, M. (1977) Science (Wash. DC) 198, 300-302]. The high concentration of somatostatin and other neuropeptides in milk implies either an active concentrating mechanism in the mammary gland or an additional extrahypothalamic source for the synthesis and release of these peptides.     

Outer membrane vesicles from Neisseria meningitidis: effects on cytokine production in human whole blood

The Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine consists of outer membrane proteins (OMPs) as main antigens with significant amounts of lipopolysaccharide (LPS; 5-9% relative to protein). We have studied the ability of this OMV vaccine preparation to induce secretion of pro-inflammatory cytokines, tumour necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8) and anti-inflammatory cytokines, interleukin 4 (IL-4), interleukin 10 (IL-10) and interleukin 13 (IL-13) in a human whole blood model. Plasma levels of TNF-alpha, IL-1beta, IL-6 and IL-8 were massively increased; mean peak levels of TNF-alpha 44 696+/-7764, IL-1beta 38 043+/-5411, IL-6 10 057+/-1619 and IL-8 30 449+/-5397 pg/ml were obtained with an OMV-LPS concentration of 1 microg/ml; corresponding levels in control plasmas were below the detection limit of the assay. Mean maximal level of IL-10 (2540+/-144 pg/ml) was obtained at OMV-LPS concentration of 10 microg/ml, after 24 h; while the level in control plasma was below detection limit. OMV-LPS did not induce release of IL-4 and IL-13 in doses from 0.001-10 microg/ml. The present results show that OMVs from meningococci have potent pro-inflammatory properties and are likely to contribute to the observed local and systemic inflammatory effects.     

Plasma transforming growth factor beta1 as a biomarker of psoriasis activity and treatment efficacy.

Transforming growth factor-beta(1) (TGFbeta(1)) is thought to be an inhibitor of the keratinocyte hyperproliferation associated with psoriasis. The aim of this study was to evaluate plasma TGFbeta(1) and TGFbeta(2) concentrations in psoriatic patients as possible indicators of treatment efficacy. TGFbeta concentrations were measured in the plasma of 26 patients with psoriasis using an enzyme immunoassay and analysed with respect to the psoriasis area and severity index (PASI) before and after treatment with salicylic acid and/or sulphur followed by dithranol ointment. Baseline plasma concentrations of both TGFbeta(1) and TGFbeta(2) (20.3+/-2.2 ng ml(-1) and 0.14+/-0.02 ng ml(-1), respectively) did not differ significantly from control values (18.3+/-1.6 ng ml(-1) and 0.14+/-0.03 ng ml(-1), respectively). However, a significant positive correlation (r=0.69) between the baseline PASI and TGFbeta(1), but not TGFbeta(2), values was demonstrated. The pretreatment TGFbeta(1) concentration in patients with a PASI >/=15 (26.6+/-3.2 ng ml(-1)) was significantly higher than control values. There were no significant elevation of pretreatment TGFbeta(1) concentrations in patients with a PASI<15, or with respect to TGFbeta(2) in both groups. Treatment caused a significant decrease in TGFbeta(1), but only in patients with a PASI>/=15. Patients with baseline TGFbeta(1) concentrations exceeding the mean of the control group had a PASI value that was significantly higher than that of patients with a TGFbeta(1) concentration below the mean of the controls. These results confirmed an association between plasma TGFbeta(1) concentration and psoriasis severity, and demonstrated its normalization during treatment. Measurement of TGFbeta(1) in plasma should be considered as a possible biomarker of psoriasis activity during its management.     

A rare allele combination of the interleukin-1 gene complex is associated with high interleukin-1 beta plasma levels in healthy individuals

Increases in the plasma levels of the inflammatory cytokines can be detected in various infectious and inflammatory diseases, but in healthy individuals these levels are in most cases low or undetectable. There is now increasing evidence that genes of the inflammatory cytokines are polymorphic and the various alleles may differ in their capability to produce the cytokine. We have measured the plasma levels IL-1 beta of 400 healthy blood donors and correlated these to the genotype (biallelelic base exchanges at the position - 889 of the IL-1 alpha gene, and at the position - 511 of the IL-1 beta gene and the pentaallelic VNTR in the second intron of the IL-1Ra gene). The median concentration of IL-1 beta was 5.8 pg/ml (upper and lower quartiles 2.2-13.6). The polymorphisms of the IL-1 beta and IL-1 Ra genes did not have any significant influence on the IL-1 beta levels, but the IL-1 alpha 2.2 homozygotes (32/400 blood donors) had significantly elevated levels (median 7.0 pg/ml, quartiles 2.2-22.4, one-way ANOVA p < 0.008 as compared to the IL-1 alpha 1.1 homozygotes and p < 0.02 as compared to the IL-1 alpha 1.2 heterozygotes). This effect of IL-1 alpha 2.2 homozygosity was more pronounced in donors, who also were carriers of the IL-1 beta allele 2. Thus these data suggest that this allele combination has a regulatory effect on basal IL-1 beta production.     

Circulating oestrogen concentrations during pregnancy in the African elephant (Loxodonta africana)

Oestrone, oestradiol-17 beta and oestriol were measured in plasma samples from non-pregnant and pregnant African elephants shot in the wild. Enzymic hydrolysis of plasma showed that approximately 90 and 96% of the total (i.e. conjugated plus unconjugated) concentrations of oestrone and oestradiol-17 beta, respectively were represented by conjugated hormones. Unconjugated oestrogens remained low (less than 50 pg ml) in all samples, with no distinction between non-pregnant and pregnant animals. Levels of total oestrone during pregnancy varied between 160 and 594 pg/ml but were not significantly different from non-pregnant values. Total oestradiol-17 beta concentrations were significantly elevated during pregnancy (P less than 0 X 01) and, despite considerable individual variation (193-1428 pg/ml), were consistently higher than non-pregnant values after 6 months of gestation. The elevated levels of oestradiol-17 beta resulted in a reversal of the total oestradiol-17 beta: oestrone concentration ratio at about 6 months of pregnancy. Concentrations of total oestriol did not exceed 103 pg/ml. An indirect method of measurement indicated that oestradiol-17 beta sulphate was probably the most abundant circulating oestrogen during pregnancy in the African elephant.     

Beta-endorphin-like and alpha-MSH-like immunoreactivities in human milk

We measured with radioimmunoassay the beta-endorphin-like and alpha-MSH-like immunoreactivities in milk and plasma of 8 lactating women. Mean beta-endorphin concentrations ( +/- SD) were 16.6 +/- 6.7 fmol/ml in milk and 9.9 +/- 4.1 fmol/ml in plasma. alpha-MSH concentrations (mean +/- SD) were 39.4 +/- 15.5 pg/ml in milk and 18.2 +/- 8.4 pg/ml in plasma. The concentrations of both peptides in milk were significantly (p less than 0.05) higher than in plasma. No significant correlation between milk and plasma concentrations of these peptides was found.     

Bombesin, neurotensin and pro-gamma-melanotropin immunoreactants in human milk

The concentration of bombesin-like, neurotensin-like and pro-gamma-melanotropin-like immunoreactants in human skim milk was measured by radioimmunoassay and found to be 235 pg/ml (mean, n = 13, range 60-430 pg/ml), 63 pg/ml (mean, n = 13, range 20-105 pg/ml) and 2.4 ng/ml (mean, n = 6, range 1.2-5 ng/ml), respectively. The concentrations were 5-10 times higher than in plasma. High performance liquid chromatography showed that the neurotensin and pro-gamma-melanotropin immunoreactants co-eluted with the authentic peptides. Bombesin gave three peaks, one co-eluting with authentic bombesin and one with porcine gastrin releasing peptide 14-27, whereas another one had a shorter elution time, suggesting a less hydrophobic fragment, possibly even smaller than gastrin releasing peptide 14-27.     

Atrial natriuretic peptide in the sheep

To study atrial natriuretic peptide (ANP) physiology in the chronically catheterized pregnant sheep model we developed a heterologous radioimmunoassay for ovine ANP using an antiserum raised against 1-28 human ANP. This antiserum (Tor I) is specific for the aminoterminus of the human ANP molecule and shows little cross reaction with any carboxyterminus ANP fragments. Ovine ANP immunoreactivity was characterized using this antiserum and a commercially available carboxyterminus ANP antiserum obtained from Peninsula Laboratories. Each antiserum detected 2 peaks of immunoreactivity in ovine atrial extracts chromatographed on a Biogel P-10 column. The minor peak migrated at a position close to 125I-human ANP whereas the major peak represented a larger molecular weight species of ANP. Examination of gel filtration eluates of ovine plasma extracts showed one immunoreactive ANP peak using the Tor I assay system and 2 peaks with the Peninsula Laboratories assay. Plasma immunoreactive ANP levels were determined in 9 sheep using both radioimmunoassay systems. Mean (+/- SEM) levels were similar using the Peninsula Laboratories and the Tor I assay systems (57 +/- 8 pg/ml versus 43 +/- 4 pg/ml, P greater than 0.05). Using the Tor I antiserum, fetal plasma immunoreactive ANP levels were found to be significantly higher than maternal levels (188 +/- 17 versus 48 +/- 8 pg/ml, P less than 0.01) whereas pregnant and nonpregnant adult sheep had similar plasma immunoreactive ANP levels (48 +/- 8 versus 43 +/- 4 pg/ml, P greater than 0.05). Disappearance curves of synthetic human ANP from the plasma of maternal and fetal sheep were assessed using both immunoassay systems and found to be similar.     

Concentrations and origin of oxytocin in breast milk

Samples of human milk obtained from lactating women in the early postpartum period were assayed for oxytocin concentrations by specific RIA, following extraction procedures with Florisil. Mean oxytocin concentrations in human milk at postpartum day 1 to 5 were 4.5 +/- 1.1, 4.7 +/- 1.1, 4.0 +/- 1.3, 3.2 +/- 0.4, 3.3 +/- 0.6 microunits/ml (+/- SE), respectively. Oxytocin levels in milk were significantly increased by nursing (3.1 +/- 0.6, 5.3 +/- 1.0 microunits/ml, respectively). 3H-oxytocin in human milk was stable even after incubation at 37 degrees C for 2 hours. The dilution curve for milk was parallel to the curve for the standard oxytocin. The chromatographic fraction of immunoreactive oxytocin was identical to that of 3H-oxytocin. 3H-oxytocin was administered to lactating rats. Radioactivity in the neonatal gastric contents and plasma were 12.8% and 4.4% of the counts in the maternal plasma. It was made clear that oxytocin is stable in milk and that oxytocin in maternal blood can be transferred to mik and then to neonates.     

Testicular endocrine function, seasonality and semen quality of the stallion

To gain further information on gonadal function of the stallion, concentrations of testicular steroids in blood plasma (bpl) and seminal plasma (spl) and their distribution in the ejaculate were determined. Blood and semen samples from a total of 11 stallions were collected from November to July. Estrone (E1), estrone sulfate (E1S), estradiol-17beta (E2beta) and testosterone (T) were determined in bpl and spl, and in addition androstenedione (A), dehydroepiandrosterone (DHEA) and 5alpha-dihydrotestosterone (5alpha-DHT) were measured in spl. At certain points of time, aliquots of an ejaculate were centrifuged, washed and the distribution of E1, E1S, E2beta and T into seminal plasma and the sperm fraction was assessed. Hormone assay was by RIA, partly after prior separation by HPLC. Mean concentrations (X(g) x DF) were as follows: E2beta (bpl) 31.1 (1.16), (spl) 24.2 (1.42) pg ml(-1); E1 (bpl) 143.3 (1.21), (spl) 117.7 (1.53) pg ml(-1); E1S (bpl) 157.3 (1.44), (spl) 2.92 (1.42) ng ml(-1); T (bpl) 570.6 (1.43), (spl) 23.1 (1.68) pg ml(-1); A (spl) 17.9 (1.39) pg ml(-1); DHEH (spl) 12.4 (1.51) pg ml(-1); 5alpha-DHT (spl) 9.7 (1.29) pg ml(-1). Except for E2beta and A in seminal plasma, a seasonal pattern was established for all other steroids with lowest mean values occurring from November to April. From the semen parameters determined, only motility was correlated to season. There was a higher correlation among oestrogen in blp than in spl and the only correlation identified between oestrogenic and androgenic steroids was between T and E2beta in blp. In spl, T was correlated with A and 5alpha-DHT. T was the dominant free steroid in bpl while it was E1 in spl; T and E1S concentrations were about 23- and 54-fold lower in spl compared to bpl with E1S, however, showing the highest absolute values in both fluids. In the fractionated ejaculate an association of free oestrogens, particularly E2beta, with spermatozoa was observed.     

Secretion of unconjugated estrone during pregnancy and around parturition in goats

The secretion of unconjugated estrone and its production site in pregnant goats were investigated in vivo. The mean estrone concentration (n = 15) in the peripheral plasma increased gradually, being 83 pg/ml on Day 40 and 483 pg/ml on Day 140 after mating. The estrone concentration increased rapidly after Day 2 before partum, reaching a peak at parturition (2370 pg/ml), and falling to 171 pg/ml at Day 1 post partum. The concentrations of estrone from the umbilical vein and umbilical artery did not differ from that found in the maternal jugular vein, suggesting that the fetus does not take part in estrogen production. The estrone concentration from the uterine vein after the fetus was removed was higher than the concentrations found in the maternal jugular vein and umbilical artery. In the placental tissue, a high concentration of estrone (18157 pg per gram of wet tissue) was detected. These findings suggest that the main production site of unconjugated estrone is the placenta.     

Regulation of transforming growth factor-beta secretion by human peritoneal mesothelial and ovarian carcinoma cells

This study was conducted to compare the secretion of TGF-beta isoforms by human ovarian carcinoma (OVCA) cell lines (n=12) and human peritoneal mesothelial cells (HPMC;n=6) and to examine the regulation of their production by inflammatory cytokines. TGF-beta isoforms were furthermore analysed in OVCA-associated ascitic fluids. HPMC constitutively produced considerable amounts of TGF-beta1 (median 42 pg/10(5)cells; range 7-98) but only minimal amounts of TGF-beta2 (median 0.8 pg/10(5)cells; range 0-1.5). Treatment of HPMC with IL-1beta (10 ng/ml) resulted in a significant elevation of the secretion of both TGF-beta1 (median 187 pg/10(5)cells; range 71-264;P<0.001) and TGF-beta2 (median 1.8 pg/10(5)cells; range 0-13;P<0.01). In OVCA TGF-beta1 and TGF-beta2 were detected in 7/12 and 11/12 of the cell lines, respectively. The levels detected varied widely for TGF-beta1 (median 25 pg/10(5)cells; range 0-410) as well as for TGF-beta2 (median 14 pg/10(5)cells; range 0-419) and there was no correlation between the two isoforms. In contrast to HPMC, TGF-beta secretion by OVCA was not affected by any of the inflammatory cytokines tested. TGF-beta3 could not be detected in supernatants, neither in OVCA nor in HPMC. In ascitic fluids the median level of TGF-beta1 (median 5443 pg/ml; range 737-14687) was 10-fold higher than the level of TGF-beta2 (median 545 pg/ml; range 172-3537). The present data provide a model for the analysis of the molecular mechanisms of aberrant TGF-beta production by OVCA and support the hypothesis that HPMC are an important source of ascitic TGF-beta.     

Determination of cabergoline and L-dopa in human plasma using liquid chromatography-tandem mass spectrometry

We determined cabergoline and L-dopa in human plasma using liquid chromatography-mass spectrometry with tandem mass spectrometry (LC-MS-MS). The deproteinized plasma samples with organic solvent or acid were analyzed directly by reversed-phase liquid chromatography. Using multiple reaction monitoring (MRM, product ions m/z 381 of m/z 452 for cabergoline and m/z 152 of m/z 198 for L-dopa) on LC-MS-MS with electrospray ionization (ESI), cabergoline and L-dopa in human plasma were determined. Calibration curves of the method showed a good linearity in the range 5-250 pg/ml for cabergoline and 1-200 ng/ml for L-dopa, respectively. The limit of determination was estimated to be approximately 2 pg/ml for cabergoline and approximately 0.1 ng/ml for L-dopa, respectively. The method was applied to the analysis of cabergoline and L-dopa in plasma samples from patients treated with these drugs. The precision of analysis showed coefficients of variation ranging from 3.8% to 10.5% at cabergoline concentration of 13.8-26.2 pg/ml and from 2.9% to 8.9% at an L-dopa concentration of 302.5-522.1 ng/ml in patient plasma. As a result, the procedure proved to be very suitable for routine analysis.     

Endometrial tissue and plasma concentrations of 5-androstene-3 beta, 17 beta-diol during the menstrual cycle in normal premenopausal and perimenopausal women

A radioimmunoassay for 5-androstene-3 beta, 17 beta-diol (ADIOL) in human endometrium and plasma is described. The recognised criteria of reliability have been fulfilled. Plasma and endometrial tissue concentrations of ADIOL were determined in samples obtained from normal premenopausal and perimenopausal women (average ages 37 and 48 years respectively) at different phases of the menstrual cycle. In perimenopausal women plasma concentrations of ADIOL did not vary throughout the cycle (proliferative phase: 411 +/- 95 (SEM) pg/ml; secretory phase: 462 +/- 28.5 (SEM) pg/ml). For the premenopausal group the pattern was similar (proliferative phase: 568.4 +/- 56.9 (SEM) pg/ml; secretory phase: 663.1 +/- 64.7 (SEM) pg/ml) although a significant difference (P less than 0.05) was noted between late proliferative and late secretory phase levels in these women. A different pattern was observed for endometrial tissue concentrations of ADIOL. In both groups of women a significant (3-4-fold) increase occurred during the secretory phase. There was no apparent relationship between plasma and tissue concentrations of ADIOL either during the proliferative or the secretory phase. There was, however, an age associated decrease for both tissue and plasma ADIOL. Theories are proposed to account for the increase in ADIOL concentration during the luteal phase.