Cortisol Rate Research Articles

A Mathematical Model For The Special Effects Of Phosphatidylserine On Endocrine Reaction To Reasonable Concentration Exercise In Healthy Male Subjects

In this study, we implement a three-parameter Weibull-G exponential model analysis to analyse the impact of short-range supplementation with a modest dosage of cortisol, lactate, growth hormone and testosterone plasma attentions in healthy male profiles before, during, and after moderate intensity practice.PS supplementation facilitates a desirable athlete state of hormones through stepping up at the rates of cortisol. Ultimately, we conclude that the application part coincides with a mathematical model and the result is linked to the medical report. In the future, this paper will be very beneficial in the medicinal field.

Impact of Adiposity and Fat Distribution on the Dynamics of Adrenocorticotropin and Cortisol Rhythms.

Obesity impacts many hormonal systems, including pituitary hormones, as well as insulin and leptin. In this review we discuss articles which investigate the influence of obesity on the hypothalamic-pituitary-adrenal (HPA) axis. Different techniques have been used to assess the function of the HPA-axis in obesity, including measuring fasting and/or late evening levels of adrenocorticotropic hormone (ACTH) and (free) cortisol in plasma and saliva, studying feedback with dexamethasone or cortisol, and evaluating responsiveness of the system to corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) or ACTH 1-29. In addition, more elaborate studies investigated 24-h secretion patterns, analyzed with deconvolution techniques to quantitate pulsatile secretion rates of cortisol and less often ACTH. Other investigators used timed infusions of labeled cortisol for the estimation of the 24-h secretion rate, clearance rate and distribution volume. Many studies relied on the 24-h urinary excretion of free cortisol, but for quantitation of the 24-h secretion, measurement of all cortisol-derived metabolites is required. Several studies have applied modern liquid chromatography-tandem-mass spectrometry techniques to measure these metabolites. The picture emerging from all these studies is that, first, ACTH secretion is amplified, likely via enhanced forward drive; and, second, serum cortisol levels are normal or even low, associated with a normal 24-h cortisol secretion per liter distribution volume determined by deconvolution, but enhanced when based on the increased total distribution volume associated with obesity. Increased cortisol secretion was also established by isotope dilution studies and reports based on the measurement of all urinary cortisol metabolites. The responsiveness of the adrenal gland to ACTH is diminished. The studies do not address quantitative aspects of cortisol-cortisone metabolism on individual organs, including liver, central and peripheral fat, intestine, skin, and muscle.

Alteration of placental type 2 11β-hydroxysteroid dehydrogenase expression and activity by lead

Alteration of placental type 2 11β-hydroxysteroid dehydrogenase expression and activity by lead

Glucocorticoids Turn Over Slowly in Human Adipose Tissuein Vivo

Lipophilic plasma glucocorticoids are thought to gain rapid access to intracellular compartments in adipose tissue. In other organs, transport can be regulated in a steroid- and tissue-specific manner. Moreover, 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) generates additional cortisol within adipose. The aim was to measure the rate of exchange of cortisol between plasma and adipose for comparison with rates of intracellular cortisol generation by 11βHSD1. With ethical approval, otherwise healthy females (n = 6) undergoing hysterectomy for benign indications were infused with tracer 9,11,12,12-[(2)H](4)cortisol (d4-cortisol). Adipose biopsies and peripheral venous samples were obtained during surgery after 3.9-5.5 h of infusion. Glucocorticoids were quantified using liquid chromatography tandem mass spectrometry. In plasma, d4-cortisol concentrations and appearance rates of cortisol and d3-cortisol (reflecting 11βHSD1 activity) did not change during surgery. In both omental and sc adipose, cortisol concentrations were lower than in plasma, consistent with differences in corticosteroid binding globulin, and enrichment with d4-cortisol was low (sc, 7.2 ± 0.6%; omental, 7.4 ± 0.7%; vs. plasma, 15.5 ± 1.0%). The rate of accumulation of d4-cortisol in adipose depots was 0.5 ± 0.1 (sc) and 0.4 ± 0.1 (omental) nmol/kg · h, and the proportion of intraadipose cortisol replaced each hour only 10.7 ± 1.0 and 10.4 ± 0.7%, respectively. The contribution of 11βHSD1 to this turnover could not be quantified because very little substrate d3-cortisone accumulated in adipose during infusion. Slow turnover of the adipose glucocorticoid pool suggests that rapid acute fluctuations in circulating cortisol are not reflected in adipose, so that 11βHSD1 activity (previously estimated to generate 9 nmol cortisol/kg · h in sc adipose) may play a relatively important role in modulating activation of glucocorticoid receptors.

Adverse Effect of Phenytoin on Glucocorticoid Replacement in a Child with Adrenal Insufficiency

Chronic administration of antiepileptic agents such as phenytoin can increase clearance rates of cortisol and synthetic glucocorticoids through hepatic microsomal enzyme induction. However, data concerning an adverse interaction between antiepileptic and steroid drugs are scarce. We herein report an adolescent boy with primary adrenal insufficiency that developed glucocorticoid deficiency after added phenytoin treatment. The patient had an increased requirement for hydrocortisone replacement, and two episodes of vomiting, hyponatremia and mild hypoglycemia. His ACTH levels were markedly elevated. Fifteen days after stopping phenytoin, his serum ACTH concentration returned to normal range. Even though the hydrocortisone dose was gradually decreased, hyponatremia and vomiting have not recurred. In conclusion, we suggest that drugs such as phenytoin affecting hepatic clearance of synthetic glucocorticoids and mineralocorticoids should not be preferred for therapy in patients with adrenal insufficiency. If their use is vital, one should be aware of increased replacement requirements for steroid drugs, and patients should be closely monitored.

Baseline Cortisol Levels Predict Treatment Outcomes in Chronic Fatigue Syndrome Nonpharmacologic Clinical Trial

ABSTRACTObjective: Understanding how nonpharmacologic interventions differentially affect the subgroups of patients with chronic fatigue syndrome (CFS) might provide insights into the pathophysiology of this illness. In this exploratory study, baseline measures of normal versus abnormal cortisol were compared on a variety of immune markers and other self-report measures. Normal versus abnormal cortisol ratings were used as predictors in a nurse-delivered nonpharmacologic intervention. Methods: Participants diagnosed with CFS were assigned to 6-month nonpharmacologic interventions. Individuals were classified as having abnormal or normal cortisol levels on the basis of scores over the five testing times. Cortisol levels were considered abnormal if they continued to rise, were flat, or were at abnormally low over time. Results: Across interventions, those with abnormal cortisol at the baseline appeared not to improve over time, whereas those with normal baseline cortisol evidenced improvements on a number o...

Changes in excretion rates of stress hormones in medical staff exposed to electromagnetic radiation

The aim of this paper is to study the effect of electromagnetic radiation (EMR) on the excretion rates of stress hormones of medical staff in physiotherapy. The excretion rates of stress hormones cortisol, adrenaline and noradrenaline were followed during morning shift in 15 female physiotherapists using RIA kits and a spectrofluorimetric method. The mean number of treatments with EMR emitting devices per month and the emission of each device was assessed. A control group of nurses, matched by age, sex and work task was used. The psychosocial factors were evaluated and no differences between the two groups was found. Calculations of the individual EMR exposure show levels above the ICNIRP guidelines. Significantly higher excretion rates of cortisol, adrenaline and noradrenaline among the studied physiotherapists in comparison with the control group of nurses were found. In conclusion, our data showed that EMR influenced the excretion rates of stress hormones of medical staff in physiotherapy.

Effect of Pro-inflammatory Cytokines on Expression and Activity of 11β-Hydroxysteroid Dehydrogenase Type 2 in Cultured Human Term Placental Trophoblast and Human Choriocarcinoma JEG-3 Cells

11Beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) is thought to act as a placental barrier protecting the fetus from high levels of maternal cortisol. On the other hand, intrauterine infection is one of the main causes of preterm birth and adverse fetal outcome, and pro-inflammatory cytokines may contribute to these adverse effects. However, the effect of pro-inflammatory cytokines on 11beta-HSD2 is still not clear. Therefore, we have evaluated the effect of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) on 11beta-HSD2 in cultured human placental trophoblast and in human choriocarcinoma JEG-3 cells. Placental trophoblast cells were isolated from human term placenta. Placental trophoblast cells and JEG-3 cells were treated with TNF-alpha (0.1-10 ng/mL) or IL-1beta (0.1-10 ng/mL). Real-time reverse transcription polymerase chain reaction and Western blot were used to study the regulation of 11beta-HSD2 expression. 11beta-HSD2 activity was determined by measuring the rate of cortisol to cortisone conversion in the culture medium using thin-layer chromatography (TLC). In placental trophoblast, TNF-alpha and IL-1beta down-regulated 11beta-HSD2 mRNA expression and activity (both P <.05). The protein level was decreased only with IL-1beta (P <.05). In JEG-3 cells, 11beta-HSD2 mRNA was decreased by TNF-alpha but up-regulated by IL-1beta, with no significant change in protein expression and activity. Our results suggest caution in interpreting data using JEG-3 cells. However, our studies with primary trophoblast suggest that TNF-alpha and IL-1beta may increase the amount of cortisol crossing to the placenta and fetal circulation by attenuating 11beta-HSD2 activity, potentially contributing to preterm labor and altered fetal outcome in uterine infection.

Production rates of cortisol in obesity determined by stable isotope dilution/mass spectrometry

Production rates of cortisol in obesity determined by stable isotope dilution/mass spectrometry

Metabolismo oxidativo de neutrófilos em ovelhas naturalmente infectadas por nematódeos gastrintestinais e correlação entre nível sérico de cortisol e carga parasitária

Estudaram-se as relações entre o metabolismo oxidativo dos neutrófilos, os níveis séricos de cortisol e a carga parasitária estimada pela contagem de ovos por grama de fezes (OPG) no final da gestação, durante a lactação e após o desmame de ovelhas naturalmente infectadas por nematódeos gastrintestinais. Utilizaram-se 22 ovelhas da raça Suffolk, homogêneas quanto à idade (três a quatro anos), número de parições (terceira) e época de parição. O cortisol sérico foi determinado por radioimunoensaio e o metabolismo oxidativo dos neutrófilos pelo teste de redução do tetrazólio nitroazul (NBT). Os maiores valores de OPG foram observados na quinta semana de lactação, e as maiores taxas de cortisol e de redução do NBT ocorreram na quarta semana pós-desmame. Verificou-se correlação positiva (r = 0,52; P&lt;0,05) entre a capacidade dos neutrófilos reduzirem o NBT e a concentração sérica de cortisol no período pré-parto. Próximo ao parto o metabolismo oxidativo dos neutrófilos diminuiu. Após o desmame a correlação entre o OPG e o teste de redução do NBT foi negativa (r = -0,39; P&lt;0,01). A diminuição do OPG observada após o desmame coincidiu com o aumento da capacidade de os neutrófilos reduzirem o NBT, indicando que animais com melhor resposta imune pós-desmame possuem neutrófilos com metabolismo oxidativo maior e menor carga parasitária.

Placental metabolism of cortisol at mid- and late gestation in swine.

An experiment was conducted in pigs to determine the source of fetal cortisol at 50 (n = 5) or 100 days (n = 4) of gestation (term = 114 days). Equilibrium concentrations of tritiated cortisol were achieved, and all hormonal measures were made at 110, 130, 140, and 150 min in anesthetized pigs. Maternal plasma cortisol did not differ (p = 0.48) between 50 (70.2 +/- 7.4 ng/ml; mean +/- SEM) and 100 days (62.4 +/- 5.8 ng/ml). Conversely, fetal cortisol increased (p = 0.048) between 50 (8.5 +/- 2.5 ng/ml) and 100 days (24.2 +/- 4.2 ng/ml), and, at each gestational age, values were lower (p = 0.001) than those in maternal plasma. Plasma cortisone (15.1 +/- 2.3 ng/ml) did not change with gestational age (p = 0.42) in either compartment (maternal or fetal), nor did it differ between compartments (p = 0.08). Maternal cortisol accounted for 22.8 +/- 2.0% of fetal cortisol at 50 days of gestation, and this contribution decreased (p < 0.001) to 5.87 +/- 0.8% at 100 days. At both ages, maternal cortisol accounted for almost 50% of fetal cortisone. Metabolism of maternal cortisol by the entire uterofetoplacental unit was 8.4 +/- 1.7% at 50 days and 7.5 +/- 2.4% at 100 days (p = 0.76). The maternal metabolic clearance rate of cortisol increased 44% (p = 0.003) between 50 and 100 days (1.49 +/- 0.4 vs. 2.15 +/- 0.2 L/min). Hence at these gestational ages, the fetus--presumably the fetal adrenal--is the primary source of fetal plasma cortisol. The major contribution of maternal cortisol to fetal cortisone strongly suggests the presence of porcine placental 11 beta-hydroxysteroid dehydrogenase activity. Further, factors constituting the placental "barrier" that metabolize maternal cortisol to cortisone and other products may be major regulators of porcine fetal plasma cortisol and cortisone.

Pituitary-adrenal responses to repeated small hemorrhage in conscious dogs.

Potentiated pituitary-adrenocortical responses to the second of two identical small hemorrhages, spaced 24 h apart, are seen in the pentobarbital sodium-anesthetized dog. To investigate the role of pentobarbital anesthesia in these results and to better define the range of the effect, we studied awake trained dogs with chronic adrenal venous catheters. Each dog was bled an amount between 8.7 and 21.8% of measured blood volume [131I] (MBV) over 3 min, and peripheral and adrenal blood were sampled. Blood was reinfused 1 h later, and the dogs were fed. The same hemorrhage and experimental protocol were repeated 24 h later. Steroids were assayed by high-performance liquid chromatography-ultraviolet (HPLC-UV) and adrenocorticotropic hormone (ACTH) by radioimmunoassay (RIA). Secretory rates of cortisol were calculated using measured adrenal blood flow rates. Maximal secretion of cortisol was determined after injection of 100 mU ACTH following each experiment. Dogs whose day 1 cortisol secretion after hemorrhage was submaximal (hem volume = 14.8 +/- 3.7% MBV; n = 7) showed a greater cortisol secretory response to the same hemorrhage on day 2 (P less than 0.005). This increased cortisol response on day 2 was accompanied by an increased ACTH presentation rate (APR) (P less than 0.025) and by increased adrenal sensitivity to ACTH (P less than 0.025). The increased APR was caused by both an increased venous ACTH and by an increased adrenal blood flow. If posthemorrhage cortisol secretion was maximal on day 1, ACTH, APR, and ABF were not different on the 2 days. No hemodynamic differences were seen to explain these findings. These results confirm and extend our previous results.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on the production and metabolic clearance rates of cortisol in the EEL

Studies on the production and metabolic clearance rates of cortisol in the EEL

A mechanistic model of ACTH-stimulated cortisol secretion.

Adrenal secretory rates of cortisol and arterial concentrations of adrenocorticotropin (ACTH) were measured in conscious trained dogs subjected to intravenous infusion of ACTH. To investigate the causal relation of ACTH to the secretion of cortisol, a mechanistic mathematical model based on current hypotheses of adrenocortical function was constructed and tested. It is widely believed that ACTH stimulates cortisol secretion through adenosine 3',5'-cyclic monophosphate (cAMP), which provides substrate cholesterol by activating cholesterol ester hydrolase and facilitating transport of cholesterol to the side-chain cleavage enzyme. In addition, cholesterol modulates its own synthesis by inhibiting beta-hydroxy-beta-methylglutaryl (HMG)-CoA reductase in the adrenocortical cell. These and other steps in the biosynthetic reaction sequence were described using differential equations subject to the additional constraints imposed by available measurements of intracellular quantities. The resulting model is consistent with many of the known characteristics of the canine adrenal response to ACTH. In this model, steady-state nonlinearities arise from cooperative binding of cAMP to its receptor protein and saturation of mitochondrial pregnenolone transport. The transient response is dominated by a depletable pool of intracellular free cholesterol. Other inferences based on the model are presented, and a quantifiable cellular basis for increased adrenal sensitivity to ACTH is proposed.

Effect of maternal administration of the antiestrogen ethamoxy triphetol throughout the last third of baboon gestation upon neonatal corticoid production

The present study determined in baboon neonates whether corticoid production, which is markedly different in preterm baboon neonates, newborns and adult baboons is regulated by estrogen, and therefore, altered by maternal administration of the antiestrogen ethamoxytriphetol (MER-25) throughout the final third of baboon gestation. The metabolic clearance rate (MCR), transfer constant (ρ), production (PR) and secretion (SR) rates of cortisol (F) and cortisone (E) were determined by continuous infusion of [3H] F and[14C]E in baboon neonates delivered spontaneously to untreated mothers and to mothers, which had received MER-25 p.o. (15 mg/kg BW) daily throughout the final third of baboon gestation.MCR-E exceeded (P < 0.05) MCR-F in both groups. The ρ F→E was greater than ρ E→F in neonates of untreated (3.5 fold, P < 0.005) and MER-25-treated (1.8 fold, P < 0.025) mothers. Mean (±SE) ρ F→E was lower (P < 0.01) in neonates delivered to mothers, which had received antiestrogen (29.2±4.4%) than in untreated mothers (59.7±8.9%). Mean (±SE) conversion ratio of F→E (F→E — E→F) was lower (P < 0.05) in neonates of antiestrogen-treated (13.7±5.5) than of untreated (41.9±10.9) mothers. Since ρ is the proportion of blood PR of precursor converted to product (i.e. F to E) it is evident that neonatal F and E production in baboons are influenced by maternal administration of antiestrogen. Thus, mean (±SE) PR-E was greater (P < 0.05) than PR-F in controls (6.79±1.23 (E), 3.69± 0.55 (F) μg/min/kg BW), but not in neonates of antiestrogen-treated mothers (4.51±1.12 (E), 3.56±0.98 (F) μg/min/kg BW).Assuming that MER-25 interfered with the action of estrogen in the fetus, our results suggest that estrogen, which is produced in increasing amounts into the maternal and fetal circulation with advancing baboon gestation, regulates the pattern of baboon fetal corticosteroidogenesis, a pattern which is distinct from that in newborns and adults and presumably represents maturational events leading to extrauterine self sufficiency.

Secretion and metabolism of cortisol and aldosterone during controlled hyperthermia.

1. The rates of secretion and metabolic clearance of cortisol and aldosterone in response to passive heating have been investigated in fifteen young men by the controlled hyperthermia technique combined with continuous I.V. infusion of [14C]cortisol and [3H]aldosterone. 2. During a 1 hr period of elevation of deep body temperature to 38.0 degrees C mean hepatic blood flow measured by indocyanine green clearance decreased by more than 25% compared with normothermic condition. 3. The pattern of response in hyperthermia involved decreasing plasma specific activities indicating increased adrenal secretion of both cortisol and aldosterone. 4. Aldosterone metabolic clearance rate usually decreased in hyperthermia when there was little change in the clearance rate of cortisol, but an increased aldosterone clearance rate was observed when there were significant increases in the clearance rate of cortisol. A contributing factor to elevation of plasma aldosterone concentration in the heat is the reduction in hepatic blood flow which reduces aldosterone metabolic clearance rate. 5. Suppression of the thermally induced rise in plasma cortisol concentration by dexamethasone was associated with a decrease in aldosterone clearance rate which may reflect increased availability of aldosterone-binding plasma protein. 6. Marked rises in plasma cortisol were always accompanied by simultaneous rises in aldosterone, but rises in aldosterone sometimes occurred in the absence of a rise in cortisol. We therefore suggest that ACTH stimulation plays an important, but not exclusive, role in the stimulation of aldosterone secretion during hyperthermia.

The production and secretion of cortisol by baboon neonates

The metabolic clearance rate (MCR), transfer constants (p), production (PR) and secretion (SR) rates of cortisol (F) andrortisone (E) were determined by the continuous infusion of {1,2 3H}F and {4- 14C}E into 5 neonates delivered prior to the parturition by cesarean section (164–179 days; term = 184 days) and into 5 newborns delivered spontaneously per vagina at term (166 – 187 days). In spontaneously delivered animals, MCR-E (X ± SE, 34.3 ± 7.0 1/day/kg was greater (P < 0.001) than MCR-F (14.9 ± 1.5 1/day/kg), pF to E (59.7 ± 8.9%) exceeded (P < 0.001) pE to F (17.8 ± 3.0%) and the percentage of F bound to serum proteins other than albumin (57.5 ± 6.2) was greater (P < 0.001) than that of E (27.0 ± 10.3) Although the serum E level (25.6 ± 3.6 μg/100 ml) was similar to that of F (33.5 ± 8.0 μg/100 ml), the PR-E (6.4 ± 1.3 μ/min/kg) was greater (P < 0.001) than PR-F (3.3 ± 0.5 μ/min/kg). Approximately eighty-five percent of the E and 65% of the F produced orginated by secretion. In animals delivered by cesarean section, the serum F concentration (32.4 ± 6.7 μ/100ml), pE to F (13.4 ± 2.8%) pF to E (80.0 ± 12.2%) PR-E (4.5 ± 0.2 μ/min/kg) and SR-E (3.9 ± 0.3 μ/min/kg) were not different from values for spontaneously delivered animals. Serum E levels (35.9 ± 1.6 μ/100 ml) were higher but MCR-F (6.7 ± 0.6 1/day/kg) and MCR-E (18.2 ± 0.41/day/kg) lower in neonates delivered by cesarean section. Serum Cortisol binding capacity (μg F bound/100 ml) was greater (P < 0.025) in neonates delivered by cesarean section (23.6 ± 2.6) than in spontaneously delivered animals (14.4 ± 2.0). As a result of these changes in F and E dynamics, PR-F (1.4 ± 0.3 μ/min/kg) and SR-F (0.9 ± 0.2 μ/min/kg) in neonates delivered by cesarean section were lower (P< 0.01) than corresponding values in spontaneously delivered newborns. It is concluded that the greater F secretion in animals delivered spontaneously than those delivered by cesarean section probably results from increased fetal adrenal 3β-hydroxysteroid dehydrogenase-isomerase activity, which as previously reported, occurs in late gestation in this species.

Adrenocorticotropin-Stimulated Secretion of Aldosterone and Cortisol, Computed from Plasma and Red Blood Cell Measurements*

The dynamic response of the adrenal cortex to ACTH infusion is analyzed by simulating the distribution, binding, and metabolism of cortisol and aldosterone in a multicompartmental model. The model includes the effects of temperature and cortisol concentration on aldosterone binding in plasma and the distribution between plasma and red blood cells, as verified by new observations. The secretion rates of cortisol and aldosterone were computed from serial measurements of plasma concentrations of endogenous steroids and infused tracers. The model was validated by observations after iv injection of a bolus of cortisol. Nineteen normal volunteers were studied on the fourth day on a diet containing 10 meq sodium. Endogenous ACTH was suppressed by dexamethasone, and alpha-1-24ACTH was infused at two different rates in various sequences over a 4-h period. During each hour of constant ACTH infusion, plasma cortisol continued to increase, while plasma aldosterone rose quickly, reaching a plateau within 20--30 min. Cortisol secretion approached a maximim rate after 20--30 min of ACTH infusion; the continued increase of plasma cortisol resulted from the slow equilibrium with other compartments. Aldosterone secretion rose quickly to a peak and then declined to a lower level after 20 min of ACTH infusion; the lower rate of secretion was maintained for the duration of the constant infusion of ACTH, falling abruptly within a few minutes after stopping the infusion. The characteristic differences in plasma steroid responses to various sequences of ACTH infusions can be explained by the more rapid changes in aldosterone secretion and the different clearance rates of cortisol and aldosterone, which vary with plasma cortisol concentration. The temperature at which blood is separated significantly affects plasma aldosterone measurements.

Serum cortisol levels of multiple sclerosis patients during ACTH treatment.

The adrenocortical function in 52 multiple sclerosis patients was studied and compared to that of ten healthy control subjects. The basic secretion rate of cortisol of the MS patients was within the range of normal. Reactivity of the adrenal cortex to stimulation by synthetic ACTH was markedly reduced independent of the duration of the disease with the exception of four patients who were in an early stage of the disease. No difference could be demonstrated between patients undergoing a bout and patients in a stage of remission. The pathogenetic and prognostic significance of the results of the present study are discussed.

Effect of Protein Binding on Transfer and Metabolism of Cortisol in Perfused Human Placenta*

The transfer and metabolism of cortisol and cortisone and the effect of protein binding on these processes have been investigated in vitro in the perfused human placenta. The clearance of cortisol in buffer, expressed as a fraction of the antipyrine transfer rate (clearance index), was 0.50 +/- 0.05 SEM in either direction. Extensive conversion to cortisone (85%) occurred during transfer. Addition of corticosteroid-binding globulin (CBG) in amounts sufficient to bind 50% of the cortisol reduced the clearance (0.40 +/- .026) insignificantly, whereas human serum albumin (HSA) in amounts sufficient to bind 50% of the cortisol reduced the clearance to 0.28 +/- 0.012 (P less than 0.001) even though the association constant for albumin is approximately 1000-fold less. The percent of conversion to cortisone did not change significantly with protein binding. The clearance index of cortisone from a protein-free perfusate was 0.74. With CBG and albumin in the same concentrations as used in the cortisol experiments, the binding of cortisone to CBG was 23% and its clearance was 0.70; with albumin, the binding was 45% and the clearance index was 0.45. The addition of albumin and CBG to the same perfusate resulted in a cortisol clearance equal to that obtained with perfusate containing only albumin. Binding to albumin may be more significant than binding to CBG in controlling the transfer rate of cortisol to the fetus.