Serum concentrations of ethinylestradiol, 3-keto-desogestrel, SHBG, CBG and gonadotropins during treatment with a biphasic oral contraceptive containing desogestrel.

During a cross-over study, the pharmacokinetics of ethinylestradiol (EE) and 3-keto-desogestrel (KDG) were investigated on days 7 and 22 of one cycle of treatment with two biphasic formulations containing 50 micrograms EE (7 tablets) and 50 micrograms EE + 125 micrograms desogestrel (DG) (15 tablets) (50/50 EE) or 40 micrograms EE + 25 micrograms DG (7 tablets) and 30 micrograms EE + 125 micrograms DG (15 tablets) (40/30 EE). Peak serum levels and areas under the curve of EE increased significantly by 50% between days 7 and 22 of those taking 50/50 EE, while during treatment with 40/30 EE, no difference was found between days 7 and 22. Both formulations caused identical KDG levels on day 22. There were only slight differences in the effects of both preparations on sex-hormone-binding globulin (SHBG; +150 to +160%) and on corticosteroid-binding globulin (CBG; +130 to +150%) on day 7. On day 22, the changes were more pronounced with 50/50 EE (SHBG, +310%; CBG, +240%) than with 40/30 EE (SHBG, +250%; CBG, +180%). On day 22 after discontinuation of treatment, the SHBG and CBG levels were still significantly above the control values. Using both formulations, LH and FSH levels were significantly suppressed on day 22, while on day 7 no significant reduction was observed. The rise in the EE levels between days 7 and 22 of 50/50 EE intake and the time course of the EE concentrations during treatment with 40/30 EE appear to be due to an inhibition of hepatic metabolism by the contraceptive steroids, as EE is nearly exclusively bound to albumin which does not change.     

Protein binding of the contraceptive steroids gestodene, 3-keto-desogestrel and ethinylestradiol in human serum

The protein binding of ethinylestradiol (EE2), gestodene (GEST) and 3-keto-desogestrel (KDG) has been determined by ultrafiltration in the serum of women who had either taken a gestodene (n = 37) or desogestrel (n = 28) containing oral contraceptive for a time period of at least 3 months. GEST and KDG were analyzed in individual serum pools whereas EE2 was repeatedly measured in two serum pools, each one representing one treatment group. The respective free fractions of the three steroids were 0.6 +/- 0.1% (GEST), 2.5 +/- 0.2% (KDG), 1.7 +/- 0.6% (EE2, in the gestodene-group) and 1.5 +/- 0.2% (EE2, in the desogestrel-group). EE2 was exclusively bound to albumin, whereas GEST and KDG were also bound to sex-hormone-binding globulin (SHBG). The distribution of the two progestins over the serum binding proteins was determined after heat-treatment of serum samples. For GEST, the contribution of albumin and SHBG was 24.1 +/- 9.1 and 75.3 +/- 9.1%, respectively and for KDG it was 65.9 +/- 11.9 and 31.6 +/- 12.0%, respectively. SHBG and corticosteroid-binding globulin (CBG) concentrations were measured in the serum samples obtained from both treatment groups. In the gestodene-group 180 +/- 61 nmol/l (SHBG) and 89 +/- 13 mg/l (CBG) were measured, the corresponding values in the desogestrel-group were 226 +/- 64 nmol/l (SHBG) and 93 +/- 14 mg/l (CBG). SHBG concentrations were correlated with the total concentration of GEST and its free fraction and a positive (r = 0.395) and negative (r = -0.491) correlation respectively was found. Only a weak negative correlation (r = -0.291) was found for SHBG and the free fraction of KDG in the serum. These data demonstrate that the three contraceptive steroids EE2, GEST and KDG were all bound extensively to serum proteins, however, with pronounced differences concerning their distribution over the various binding proteins.     

Comparison of serum ethinyl estradiol, sex-hormone-binding globulin, corticoid-binding globulin and cortisol levels in women using two low-dose combined oral contraceptives

The study included 69 women taking a desogestrel (n = 30)- or gestodene (n = 39)-containing low-dose combined oral contraceptive for at least 3 months. Group size was calculated to detect a difference in mean values of 80% of 1 standard deviation (alpha = 0.05, beta = 0.1). Seven serum samples were obtained up to 4 h, and 1 sample 24 h, after drug intake on 1 day between the 10th and the 21st day of the cycle. The concentrations of sex-hormone-binding globulin (SHBG), corticoid-binding globulin (CBG) and cortisol were measured in a 0- to 4-hour serum pool by radioimmunoassay. Ethinyl estradiol (EE2) levels were analyzed in single and pooled samples using anti-EE2-6 beta-carboxymethyloxime-bovine serum albumin antiserum. The area under the curves (AUC) up to 4 and 24 h and Cmax and tmax were evaluated. Statistical analysis (analysis of covariance) did not reveal a dependence of values on duration of treatment or day of cycle. Both treatments resulted in almost identical values for all parameters evaluated. The mean levels of SHBG, CBG and cortisol were in the range of 186-226 nmol/l, 89-93 mg/l and 280-281 micrograms/l, respectively. Mean maximum EE2 levels of 106-129 pg/ml were found 1.6-1.8 h after pill intake and AUC0-4 h accounted for 329-374 pg.h.ml-1. The recently reported differences in serum EE2 and CBG levels between two groups of 11 women each treated with desogestrel- and gestodene-containing pills, respectively, could not be confirmed.     

Estrone sulfate and dehydroepiandrosterone sulfate concentrations in normal subjects and men with cirrhosis.

Circulation levels of estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHAS) have been measured in plasma using a radioimmunoassay for estrone and dehydroepiandrosterone following extraction and hydrolysis of the sulfate. The mean +/- SE concentrations of E1S and DHAS in normal men were 458 +/- 25 pg/ml and 1.45 +/- 0.19 micrograms/ml, respectively. In normal women the values for days 5-7 of the cycle were 880 +/- 117 pg/ml and 1.25 +/- 0.12 micrograms/ml which were not different than the values for days 20-22 of 1195 +/- 176 pg/ml and 1.58 +/- 0.29 micrograms/ml. The mean values in post-menopausal women were 250 +/- 33 pg/ml and 0.47 +/- 0.07 micrograms/ml, both lower than the values in young women. In a group of cirrhotic men the mean values were 325 +/- 55 pg/ml and 0.38 +/- 0.12 micrograms/ml, both significantly lower than the normal values. This suggests a defect in sulfurylation in men with hepatic cirrhosis.     

Effects of synthetic ovine corticotropin-releasing factor (CRF) on plasma ACTH and cortisol in 31 normal human males

Responses of plasma ACTH and cortisol to corticotropin-releasing factor (CRF) were evaluated in 31 normal human males. 1.0 micrograms/ks of sterilized synthetic ovine CRF was administered to the subjects, aged 19 to 53 yr and weighing 50 to 78 kg, at between 9:30 a.m. and 10:30 a.m. as an intravenous bolus injection after an overnight fast. Blood specimens were drawn before and 15, 30, 60, 90 and 120 min after injection for later determination of plasma ACTH and cortisol concentrations by radioimmunoassays. Plasma ACTH and cortisol levels for all subjects rose significantly (p less than 0.001) from the basal level (mean +/- SEM, 26.8 +/- 4.5 pg/ml and 12.6 +/- 0.9 micrograms/dl) to peak levels (58.4 +/- 5.5 pg/ml and 22.9 +/- 1.0 micrograms/dl) at 30 min and at 60 min, respectively. Although the plasma concentrations of ACTH and cortisol thereafter declined gradually, the levels at 120 min (43.4 +/- 5.2 pg/ml and 18.9 +/- 0.9 micrograms/ml, respectively) were still significantly higher than the basal levels (p less than 0.001). Significant inverse correlations were observed between the basal levels of each hormone and the ratio of the peak level to the basal level (p less than 0.01), and the increases in plasma ACTH and cortisol concentrations were either not significant or much smaller for the individuals in whom the basal levels were higher than 65 pg/ml and 17.0 micrograms/dl, respectively. No serious subjective symptom was observed during the experimental period in any of the subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of hexose transport in respiration deficient hamster lung fibroblasts

The transport of [3H]2-deoxy-D-glucose (2DG) and [3H]3-O-methyl-D-glucose (3-OMG) was elevated in a respiration deficient (NADH coenzyme Q [Co Q] reductase deficient) Chinese hamster lung fibroblast cell line (G14). This sugar transport increase was related to an increased Vmax for 2DG transport, 26.9 +/- 4.2 nmoles 2DG/mg protein/30 sec in the G14 cell line vs 9.5 +/- 0.6 nmoles 2DG/mg protein/30 sec in the parental V79 cell line. No differences were observed in their respective Km values for 2DG transport (3.9 +/- .6 vs. 3.0 +/- .13 mM). Factors which increase sugar transport (e.g., glucose deprivation, serum or insulin exposure) or decrease sugar transport (e.g., serum deprivation) in the parental V79 cell line had little effect on sugar transport in the G14 respiration deficient cell lines. Amino acid transport, specific 125I-insulin binding to cells, and insulin-stimulated DNA synthesis, however, were similar in both cell lines. Exposure of both cell lines to varying concentrations of cycloheximide (0.1-50 micrograms/ml) for 4 h resulted in differential effects on 2DG transport. In the parental cell line (V79) low cycloheximide concentrations resulted in decreased 2DG transport, while higher concentrations (greater than or equal to 1 microgram/ml) resulted in elevated 2DG transport. In the G14 cell line, 2DG transport decreased at all concentrations of cycloheximide (up to 50 micrograms/ml). The data indicate that the G14 mutant has been significantly and specifically affected in the expression of sugar transport activity and in the regulatory controls affecting sugar transport activity.     

Possible involvement of endogenous beta-endorphin in the pathophysiological mechanisms of Pichinde virus-infected guinea pigs.

Previously, we demonstrated that naloxone, an opiate antagonist, prolonged survival of strain 13 guinea pigs infected with Pichinde virus. Thus, endogenous opiates may be involved in the pathogenesis of this viral disease. To determine whether endogenous opiate levels were affected by Pichinde viral infection, beta-endorphin concentrations in plasma and cerebrospinal fluid (CSF) of normal and infected strain 13 guinea pigs were measured by radioimmunoassay. Cerebrospinal fluid beta-endorphin concentrations were 78.0 +/- 13.2 pg/ml on postinoculation day (PID) 7, 59.0 +/- 5.6 pg/ml on PID 12, and 58.8 +/- 5.4 pg/ml on PID 14. These values were significantly higher than baseline levels of CSF beta-endorphin: 30.8 +/- 1.9 pg/ml. Plasma beta-endorphin concentrations of infected animals increased significantly to 202.1 +/- 17.9 pg/ml on PID 7 and to 154.2 +/- 21.4 pg/ml on PID 12 from a mean baseline value of 84.2 +/- 13.1 pg/ml. After a primer intravenous injection of beta-endorphin (10, 15, or 30 micrograms/kg), followed by constant infusion of beta-endorphin (15, 45, or 90 micrograms/kg.hr) to control noninfected guinea pigs, heart rate (except with the lowest dose) and mean blood pressure decreased markedly. Under these experimental conditions, concentrations of plasma and CSF beta-endorphin increased simultaneously with different magnitude. Because both Pichinde viral infection and beta-endorphin administration produced a similar trend of cardiovascular disturbances, leading to hypotension and bradycardia, increased concentrations of plasma and CSF beta-endorphin may play a partial role in the pathophysiological mechanisms of Pichinde virus infection.     

Ciprofloxacin concentrations in serum, bone and bone marrow of rabbits

Ciprofloxacin concentrations were determined in serum, bone and bone marrow of rabbits. Four experimental groups of animals were examined: group A (n = 6) received a dosage of 60 mg/kg/day intramuscularly for 4 weeks, groups B (n = 6), C (n = 15) and D (n = 15) received dosages of 120 mg/kg/day subcutaneously for 2 days, 2 weeks, and 4 weeks, respectively. In the kinetic portion of the study, peak serum concentrations of ciprofloxacin measured at the 15 min sampling time were: 2.61 +/- 0.27 micrograms/ml in the 60 mg/kg/day group (group A) and 3.24 +/- 0.78 micrograms/ml in the 120 mg/kg/day group (group B). At necropsy, rabbits in group A had mean ciprofloxacin concentrations of 3.60 +/- 2.27 micrograms/ml in serum, 2.24 +/- 1.19 micrograms/g in marrow and 1.19 +/- 0.44 micrograms/g in bone. Rabbits in group B achieved mean levels of 4.02 +/- 1.23 micrograms/ml in serum, 2.48 +/- 0.79 micrograms/g in marrow, and 1.35 +/- 0.40 micrograms/g in bone. Rabbits in group C achieved mean levels of 5.65 +/- 2.16 micrograms/ml in serum, 3.74 +/- 1.33 micrograms/g in marrow and 1.92 +/- 0.94 micrograms/g in bone. Rabbits in group D achieved mean levels of 7.24 +/- 2.50 micrograms/ml in serum, 4.48 +/- 1.68 micrograms/g in marrow, and 1.93 +/- 0.54 micrograms/g in bone. Differences between mean values for the four experimental groups were not statistically significant.     

Lipid peroxidation at various estradiol concentrations in human circulation during ovarian stimulation with exogenous gonadotropins.

The aim of our study was to investigate the correlation between serum malondialdehyde levels and serum estradiol concentrations in healthy human female subjects. Nine hundred and fifty-five blood samples, from infertile women undergoing controlled ovarian hyperstimulation treatment with recombinant follicle-stimulating hormone, were collected for estradiol and malondialdehyde measurements. Five groups were formed according to serum estradiol levels: Group I (< 50 pg/ml), group II (50 - 299 pg/ml), group III (300-999 pg/ml), group IV (1000-1999 pg/ml) and group V (> or = 2000 pg/ml). One-way analysis of variance was used for comparisons. Mean malondialdehyde concentrations were 1.74 +/- 0.24 mmol/ml (group I), 1.53 +/- 0.20 mmol/ml (group II), 1.69 +/- 0.24 mmol/ml (group III), 1.77 +/- 0.21 mmol/ml (group IV) and 1.86 +/- 0.20 mmol/ml (group V), respectively. Mean serum malondialdehyde level at physiological estradiol concentrations (50-199 pg/ml, group II) was significantly (p < 0.01) lower than the mean malondialdehyde levels in other groups. Mean malondialdehyde concentrations among the remaining groups did not significantly differ. Our findings suggest that in vivo lipid peroxidation might be increased when circulating estradiol concentrations are below (< 50 pg/ml) or above (> 300 pg/ml) the physiological limits. High blood estradiol levels in human female subjects during ovarian stimulation with exogenous gonadotropins could be associated with increased serum malondialdehyde concentrations.     

Serum concentrations of calcitonin and parathormone in the cord blood of premature infants

Determinations of serum calcium (Ca), calcitonin (CT) and parathyroid hormone (PTH) were carried out in mixed cord blood of 23 preterm infants. Gestational age ranged between 25 and 37 weeks. 17 of theme were vaginally delivered while 6 were delivered by emergency Caesarean section. 4 neonates died because of respiratory distress syndrome. The serum was stored at -30 degrees C until the determinations. Serum Ca levels were determined by spectrophotometry while CT and PTH levels by RIA (Immuno Nuclear Co). In cord serum the mean (M +/- SE) Ca,CT and PTH concentrations of all neonates examined were respectively: 9,9 +/- 0,6 mg/dl; 176 +/- 44 pg/ml and 1100 +/- 446 pg/ml. Serum values of CT and PTH in preterm newborns delivered by emergency Caesarean section were significantly higher than in those neonates vaginally delivered (CT: 302 +/- 115 vs 94 +/- 9 pg/ml; p less than 0.005) (PTH:2655 +/- 1857 vs 466 +/- 59 pg/ml; p less than 0.05). No differences were observed between serum CT and PTH levels in preterm neonates of different gestational age. Both CT and PTH serum concentrations were higher in neonates who died. In conclusion, the preterm neonate is able to secrete both peptides and to maintain Ca homeostasis; the mode of delivery likely affects the CT and PTH secretion; unexplainable high CT and PTH serum levels were detected in poor outcome preterm infants.     

Radioimmunoassay of testosterone in late fetal and newborn rabbit plasma, gonads and adrenal glands]

A radioimmunoassay was used for measuring testosterone in the plasma, gonads and adrenals of 28, 29, 30 and 31-day-old rabbit fetuses of both sexes and newborns. A marked sex difference was shown in the concentrations of testosterone in plasma and in gonads whereas in adrenals the levels of testosterone were low in both sexes (34 to 147 pg/10 mg). In male fetuses, plasma testosterone levels increased from the 28th (133 +/- 20 pg/ml) to the 31st day (361 +/- 119 pg/ml) of intrauterine life, reaching then the values observed in the newborns (387 +/- 73 pg/ml). Plasma from males, on the other hand contained, at all stages studied, significantly more testosterone than plasma from female fetuses (21 +/- 6 to 41 +/- 11 pg/ml) and female newborns (42 +/- 6 pg/ml). In the same way, fetal testicular testosterone concentrations varying from 1 382 +/- 218 to 2 317 +/- 333 pg/10 mg were similar to those measured in the newborns (1 940 +/- 304 pg/10 mg) and significantly higher than fetal (13 to 34 pg/10 mg) or neonatal (44 pg/10 mg) ovarian concentrations. These results showed at evidence the endocrine activity of the fetal testis during this period.     

Assay of ethynyloestradiol in human serum and its binding to plasma proteins

A radioimmunoassay for estimating both unconjugated and conjugated ethinyl estradiol (EE) in serum is described, along with a report of levels of EE attained after its administration and the binding of EE in plasma, as determined by this radioimmunoassay. Mean values for concentration of free EE were 38-87 pg/ml, 1-4 hours after administration, and by 24 hours levels in most subjects were below the sensitivity level of this assay, which is less than 25 pg/ml. Conjugated EE concentration in serum was considerably higher, with mean values of 370-770 pg/ml 1-4 hours after ingestion, decreasing slowly to mean values of 285 pg/ml at 8 hours and 100 pg/ml at 24 hours postadministration. Total EE (conjugated plus unconjugated) had a mean half-life of 3.8 hours during the period 2-8 hours after administration and 10.7 hours for the period 8-24 hours postadministration. EE in plasma was shown, by equilibrium dialysis, gel filtration on Sephadex G200, and polyacrylamide gel electrophoresis, to bind only to albumin, and no specific binding of EE occurred. The apparent association constant for the binding of EE to human serum albumin was 1.7 times 10 5 liter per mol.     

Running and shipping elevate plasma levels of beta-endorphin-like substance (B-END-LI) in thoroughbred horses

A specific RIA for beta-endorphin (B-END) was developed to measure horse plasma levels of B-END-like material (B-END-LI) during exercises and shipping. Three exercise speeds and durations were: trot at 260-300 m/min for 10 min; slow gallop at 390-420 m/min for 5 min and fast gallop at 700-800 m/min for 2 min. Blood samples were taken from 4 horses before, immediately after, 30 and 60 min after exercise. Trotting increased plasma B-END-LI from a basal level of 109 +/- 7 pg/ml to 172 +/- 22 at the end of exercise and returned to 127 +/- 17 and 107 +/- 10 pg/ml at 30 and 60 min after exercise. Similar results were obtained in slow gallop (121 +/- 6 to 210 +/- 17 then 155 +/- 8 and 131 +/- 11 pg/ml). However, fast gallop caused the greatest increase (352%) in B-END-LI to concentrations of 544 +/- 93 pg/ml and 276 +/- 74 pg/ml at 5 and 30 min after exercise. Plasma B-END-LI returned to 199 +/- 46 pg/ml in 1 hr. Sequential exercises of trot, slow and fast gallop were conducted in 6 horses. Plasma B-END-LI were 116 +/- 19 pg/ml (pre-exercise), 198 +/- 21 (trot), 361 +/- 51 (slow gallop), 500 +/- 57 (fast gallop) and 248 +/- 29, 171 +/- 24, 143 +/- 20 and 139 +/- 21 pg/ml at 0.5, 1, 2 and 3 hr, respectively, following exercises. Transportation in horse trailer also significantly increased plasma levels of B-END-LI from a basal level of 138 +/- 12 to 196 +/- 24 pg/ml within 30 min and this levels were maintained at 45 min (177 +/- 3 pg/ml). Plasma levels of B-END-LI began to decline at 60 min of shipping. These results showed that plasma B-END-LI was increased in all speeds of exercise and by shipping and returned to pre-exercise and pre-shipping level in 30 min except fast gallop which returned to pre-exercise level in 1 hr.     

Immunoreactive parathyroid hormone and calcitonin in children's cerebrospinal fluid

Cerebrospinal fluid (CSF) levels of immunoreactive parathyroid hormone (iPTH) and immunoreactive calcitonin (iCT) were measured by radioimmunoassay in 23 outpatient leukemic children on maintenance chemotherapy. These hormones were detectable in the CSF of all patients: iPTH 148 +/- 11 pg/ml (mean +/- SEM); iCT 14.3 +/- 0.8 pg/ml. iPTH and iCT were also measured in serum (iPTH 396 +/- 18 pg/ml; iCT 32.3 +/- 1.4 pg/ml). CSF values were significantly lower (p less than 0.001) than serum concentrations; no significant correlation between the two compartments was found. Our study indicates the presence of iPTH and iCT in the CSF of children.     

Transforming growth factor beta1 and soluble Fas serum levels in hepatocellular carcinoma

In this study we assessed the usefulness of serum Transforming Growth Factor-beta1 (TGF-beta1) and soluble Fas (sFas) in distinguishing liver cirrhosis (LC) with and without hepatocellular carcinoma (HCC) as compared with alpha-fetoprotein (AFP). Serum TGF-beta1 and sFas levels were measured by ELISA in 51 LC patients, 54 patients with HCC and 30 healthy donors. Considering as a cut-off limit (mean+1SD of controls) 74 pg/ml and 637 pg/ml for TGF-beta1 and sFas, respectively, we computed serum concentrations of TGF-beta1 and sFas as a score (mean+/-SD). The positive frequency of serum TGF-beta1 levels in HCC patients (54%) was greater than in LC patients (26%) and healthy donors (3%). TGF-beta1 levels were higher in HCC (1.6+/-0.5) than in LC (1.1+/-0.2) (P<0.0001) and healthy donors (0.6+/-0.2). Using a cut-off limit of 82 pg/ml (mean+2SD), the positive frequency of TGF-beta1 was 20% in HCC patients. None of the controls and LC patients had TGF-beta1 levels higher than 82 pg/ml. The positive frequency of serum sFas levels was 100% in HCC patients, 98% in LC patients and 3% in healthy controls. Serum sFas levels were higher in HCC (2.5+/-0.7) than in LC (1.9+/-0.5) (P<0. 001) and healthy donors (0.6+/-0.3). No significant change of positive frequency was obtained by setting sFas cut-off at higher levels. sFas values did not correlate with TGF-beta1 levels. No relationship was found between TGF-beta1 amounts and AFP levels. However, in the 23% of HCC patients, with normal AFP values TGF-beta1 levels were higher than the cut off. These findings suggest the potential usefulness for TGF-beta1 assay in AFP-negative HCC.     

Evaluation of biological availability and anti-arrhythmic effect of a new drug Phenytoinum "Polfa"]

Studies were performed in 15 patients with ventricular arrhythmia. During the first day, the patients received 1000 mg of a new micronised form of Phenytoinum "Polfa" or adequate dose of a foreign drug in 3 doses every 3 hours and subsequently during 10 days alternatively native or foreign drug in a daily dose 300 mg. Twenty-four EKG Holter monitoring and determination of serum drug level were carried out after a 10-day treatment; area under the curve (AUC) in one 8 h dose interval was determined. Studies have shown usefulness of a new form of Phenytoinum (Polfa). Blood serum drug levels near to the therapeutic ones were observed. Steady-state Phenytoinum concentration was 11.1 +/- 5.9 micrograms/ml and after foreign drug it was 11.7 +/- 6.1 micrograms/ml, AUC0-8 was 90.4 and 105.3 micrograms/ml/h respectively. In 9/15 patients (60%) Phenytoinum (Polfa) produced substantial improvement in the cardiac arrhythmia.     

Serum concentrations of oestradiol and progesterone, and sexual behaviour during the normal oestrous cycle in the leopard (Panthera pardus)

Three mature nulliparous female leopards were studied for 5 years. During three separate 6-month periods serum oestradiol and progesterone concentrations were measured at weekly intervals. Oestradiol was elevated over 21 pg/ml for 54 weeks during these 3 periods, and 36 oestradiol peaks (65.8 +/- 6.3 pg/ml (mean +/- s.e.m.), range 21-172 pg/ml) were identified. Daily frequency of feline reproductive behaviours averaged over each week increased from 1.9 +/- 0.2 (n = 93) during weeks with low serum oestradiol concentrations (less than 21 pg/ml) to 5.3 +/- 0.6 (n = 54) during weeks when serum oestradiol concentrations (greater than 21 pg/ml) were high. Increased serum progesterone concentrations (13-98 n/gml) were observed on 5 occasions in 2 leopards housed together. These presumptive luteal phases lasted from 1 to 5 weeks. Baseline progesterone values were 1.6 +/- 0.4 ng/ml (n = 131). No progesterone increments were observed in isolated animals, and serum concentrations remained at baseline levels. These limited observations suggest that female leopards do not require intromission to induce ovulation and luteal function. The average interval between oestradiol peaks for cycles with no progesterone increment was 3.4 weeks (range 1-6 weeks). The interval for the 3 complete cycles associated with elevated progesterone concentrations was 7.3 weeks. Analysis of sexual behaviours over the 5-year study period revealed no evidence of seasonality in these captive leopards.     

Testosterone and estradiol concentrations in serum, velvet skin, and growing antler bone of male white-tailed deer

The growth and mineralization of antlers correlate with the seasonal variation of serum androgens. Whereas seasonal levels of testosterone (T) in plasma are well established, steroid concentrations have not yet been determined in the tissues of growing antlers. Therefore, RIA was used to determine T and 17beta estradiol (E2) in serum, and three areas (tip, middle, and base) of the antler bone and the antler skin, called velvet. Blood and antler tissues of white-tailed deer (Odocoileus virginianus) were collected from May to August. The difference between levels of T and E2 among the sites was calculated using the square root transformation followed by a mixed model analysis with individual deer and an interaction of individual and year (individual(*)year) as a random factor. Concentrations of T in serum (799+/-82 pg/ml) were higher than T values in the velvet (589+/-58 pg/ml, P<0.01) and in the antler bone (538+/-58 pg/ml, P<0.001). Estradiol concentrations differed among antler tissues and serum (P<0.001) and between years (P<0.01). Estradiol concentrations in serum (25+/-25 pg/ml) were consistently lower than those in antler bone (208+/-11 pg/ml, P<0.001) and velvet (150+/-12 pg/ml, P<0.001). The E2:T ratio in serum was 1:10-60. The same ratio for the antler bone was only 1:2-3 and for the velvet 1:3.5. It is concluded that higher T and lower E2 concentrations found in plasma, as compared to antler bone or antler velvet, may indicate a partial metabolism of systemic androgens into estrogens xin the tissues of growing antlers.     

Plasma glucagon-immunoreactive components in early life in dogs

High plasma concentrations of C-terminal immunoreactive glucagon (IRG) have been found during early life in several mammalian species. We have analyzed the plasma IRG of 12 h to 60 day-old dogs in terms of the 4 peaks (IRG greater than 20,000, IRG9000, IRG3500 and IRG2000) obtained by gel filtration on Bio-Gel P-30. Significant changes with age and in response to administered agents were confined to IRG9000 and IRG3500. IRG9000 was 9-fold higher in 12-36 h old dogs than in adults (108 +/- 24 pg/ml pancreatic glucagon equivalents v. 12 +/- 3 pg/ml, mean +/- SEM) and showed a decline to 2-fold higher (27 +/- 5 pg/ml) at 31-60 days. IRG3500 was higher than in the adult only during the first 36 h of life (36 +/- 5 pg/ml v. 15 +/- 3 pg/ml). Arginine infusion (0.5 g/kg over 15 min) caused an increase in plasma levels of both IRG9000 and IRG3500 in the newborn, whereas in adult dogs only IRG3500 was increased. Insulin injection (0.2 U/kg intravenously) causing a marked hypoglycemia had no significant effect on the plasma level of any IRG component in newborn dogs. Dihydrosomatostatin infusion (10 micrograms/kg bolus +/- 90 micrograms/kg over 30 min) caused a decrease in both IRG9000 and IRG3500. The increased basal level and secretory response to arginine of IRG9000 in newborn dogs may reflect an immaturity of the A cells, whereby more of this component, which may represent a precursor of pancreatic glucagon, is secreted than in the adult. The immature A cells also appear to have an impaired secretory response to hypoglycemia.     

Indomethacin fails to alter basal or phenothiazine-induced prolactin concentrations in man.

In order to evaluate the possible role of prostaglandins in pituitary prolactin (PRL) secretion, PRL was serially measured following perphenazine (Trilafon) ingestion in 8 men before and after 5 days of indomethacin administration. Since estrogens have been shown to modulate prolactin secretion in man, serum steroids including estrone (E1), estradiol (E2), progesterone (P) and testosterone (T) were measured before and after indomethacin ingestion. Serum E1, P and T levels were similar during the pre- and post-indomethacin study periods: 56 +/- 4 (1 SEM) vs 48 +/- 5 pg/ml, 298 +/- 28 vs 315 +/- 32 pg/ml, and 8.1 +/- 0.7 vs 8.6 +/- 0.7 ng/ml, respectively. Serum E2 levels were slightly, but significantly, lower following indomethacin treatment at 30 +/- 3 vs 37 +/- 3 pg/ml (p less than .01). Basal serum PRL concentrations were unaffected by indomethacin administration (9 +/- 3 pre- vs 8 +/- 2 ng/ml post-drug treatment). Integrated perphenazine-induced PRL responses were likewise similar during the 2 study periods: 101 +/- 16 ng . hr/ml during the control period and 104 +/- 14 ng . hr/ml following indomethacin. Thus, short-term indomethacin treatment had no effect on basal or perphenazine-stimulated PRL secretion in men.