Free Hormone Levels Research Articles

Circadian and Ultradian Rhythms of Free Glucocorticoid Hormone Are Highly Synchronized between the Blood, the Subcutaneous Tissue, and the Brain

Total glucocorticoid hormone levels in plasma of various species, including humans, follow a circadian rhythm that is made up from an underlying series of hormone pulses. In blood most of the glucocorticoid is bound to corticosteroid-binding globulin and albumin, resulting in low levels of free hormone. Although only the free fraction is biologically active, surprisingly little is known about the rhythms of free glucocorticoid hormones. We used single-probe microdialysis to measure directly the free corticosterone levels in the blood of freely behaving rats. Free corticosterone in the blood shows a distinct circadian and ultradian rhythm with a pulse frequency of approximately one pulse per hour together with an increase in hormone levels and pulse height toward the active phase of the light/dark cycle. Similar rhythms were also evident in the subcutaneous tissue, demonstrating that free corticosterone rhythms are transferred from the blood into peripheral target tissues. Furthermore, in a dual-probe microdialysis study, we demonstrated that the circadian and ultradian rhythms of free corticosterone in the blood and the subcutaneous tissue were highly synchronized. Moreover, free corticosterone rhythms were also synchronous between the blood and the hippocampus. These data demonstrate for the first time an ultradian rhythm of free corticosterone in the blood that translates into synchronized rhythms of free glucocorticoid hormone in peripheral and central tissues. The maintenance of ultradian rhythms across tissue barriers in both the periphery and the brain has important implications for research into aberrant biological rhythms in disease and for the development of improved protocols for glucocorticoid therapy.

Effect of Sex and Prior Exposure to a Cafeteria Diet on the Distribution of Sex Hormones between Plasma and Blood Cells

It is generally assumed that steroid hormones are carried in the blood free and/or bound to plasma proteins. We investigated whether blood cells were also able to bind/carry sex-related hormones: estrone, estradiol, DHEA and testosterone. Wistar male and female rats were fed a cafeteria diet for 30 days, which induced overweight. The rats were fed the standard rat diet for 15 additional days to minimize the immediate effects of excess ingested energy. Controls were always kept on standard diet. After the rats were killed, their blood was used for 1) measuring plasma hormone levels, 2) determining the binding of labeled hormones to washed red blood cells (RBC), 3) incubating whole blood with labeled hormones and determining the distribution of label between plasma and packed cells, discounting the trapped plasma volume, 4) determining free plasma hormone using labeled hormones, both through membrane ultrafiltration and dextran-charcoal removal. The results were computed individually for each rat. Cells retained up to 32% estrone, and down to 10% of testosterone, with marked differences due to sex and diet (the latter only for estrogens, not for DHEA and testosterone). Sex and diet also affected the concentrations of all hormones, with no significant diet effects for estradiol and DHEA, but with considerable interaction between both factors. Binding to RBC was non-specific for all hormones. Estrogen distribution in plasma compartments was affected by sex and diet. In conclusion: a) there is a large non-specific RBC-carried compartment for estrone, estradiol, DHEA and testosterone deeply affected by sex; b) Prior exposure to a cafeteria (hyperlipidic) diet induced hormone distribution changes, affected by sex, which hint at sex-related structural differences in RBC membranes; c) We postulate that the RBC compartment may contribute to maintain free (i.e., fully active) sex hormone levels in a way similar to plasma proteins non-specific binding.

The effect of prolonged fasting on levels of growth hormone-binding protein and free growth hormone

ObjectiveThere are limited data on growth hormone-binding protein (GHBP) and free GH levels during the physiological challenge of a prolonged fast. Our aim was to explore the relationships between GHBP, free GH, total GH and non-esterified fatty acid (NEFA) levels during overnight and 24-hour fasts in healthy young adults. DesignWe measured nocturnal levels of GHBP at three time-points (22:00, 03:00, 08:00), NEFA every 60min and ultra-filtered free GH and total GH at 15-minute intervals for 10h (22:00–08:00) during an overnight and a 24-hour fast in 7 female and 4 male normal-weight subjects aged 24.8years (range: 22.8–26.9) with BMI 22.5kg/m2 (range: 18–27). ResultsSpontaneous free and total GH levels were closely related during the overnight and 24-hour fasts (r=0.99, p<0.0001 and r=0.99, p<0.0001 respectively). 24h of fasting led to an increase in levels of basal free GH (p=0.03), mean free GH (p=0.04), mean total GH (p=0.04) and NEFA (p<0.0001) whilst GHBP levels remained similar (p=0.8). Percentage free (over total) GH was similar during the overnight and prolonged fasts (p=0.3). There were no associations between levels of NEFA and free (r=0.24, p=0.5) or total GH (r=0.20, p=0.6). ConclusionsA 24-hour fast led to parallel increases in free and total GH levels whilst there was no discernable change in GHBP levels or the fraction of free GH. This suggests that GHBP plays a role in limiting variations of circulating free GH levels. NEFA levels increased during the prolonged fast but they were not correlated with free or total GH levels.

Abstract 2503: Plasma Estradiol and Testosterone Levels and Risk of Ischemic Stroke in Postmenopausal Women

Background: Large randomized trials have shown that use of exogenous estrogens with or without progestin increase the risk of ischemic stroke among women. Current data on the association between endogenous sex hormones and ischemic stroke are very limited. Data are also lacking on the association with endogenous androgens, which, through aromatization, are the primary source of endogenous estrogen in postmenopausal women. Thus, we evaluated plasma estradiol and testosterone levels and risk for ischemic stroke among women in the Nurses’ Health Study (NHS). Methods: Among 32,826 participants in the NHS who provided blood samples in 1989-1990, 405 postmenopausal women (209 never/past users and 196 current users of hormone therapy) had a confirmed diagnosis of ischemic stroke through 2006. An equal number of controls who were free of stroke during follow-up were matched for age, use of postmenopausal hormones, and smoking status. Estradiol and testosterone levels were measured by mass spectroscopy. Conditional logistic regression was used to evaluate the association of log-transformed levels of estradiol and testosterone with stroke risk, within strata of hormone therapy use. Results: Circulating estradiol was not associated with stroke risk among never/past users; the relative risk (RR) (95% confidence interval) for highest to lowest estradiol quartiles was 1.27 (0.74-2.19), when adjusted for matching factors (p trend=0.75). However, there was a nonsignificantly increased risk of stroke among current users with higher estradiol levels; conditional on matching factors, the RRs were 2.28 (1.20-4.33), 1.55 (0.81-2.96), and 1.90 (0.96-3.79), for quartiles 2-4, respectively (p for trend=0.56). No association was observed between total testosterone levels and stroke risk in either group; the RRs for highest to lowest quartiles were 0.86 (0.50-1.49) and 1.06 (0.60-1.87) in never/past and current users, respectively (p for trends ≥0.39). The associations with free sex hormone levels were similar to those observed with total circulating levels. Additional adjustment for body mass index, aspirin use, alcohol consumption, and history of diabetes, elevated cholesterol, hypertension, or coronary heart disease, as well as levels of c-reactive protein (CRP) and the total/HDL cholesterol ratio did not materially change the associations. No association was observed between total and free testosterone levels and stroke risk in either never/past or current users (p for trends ≥0.39). These associations did not vary across levels of aspirin use smoking status, or CRP (p for interactions &gt;0.05). Conclusions: Estradiol and testosterone levels were not associated with risk of ischemic stroke in this cohort of postmenopausal women.

Thyroid Hormones in Children on Antiepileptic Therapy

ABSTRACTThe aim of this study was to evaluate the thyroid function alterations in a group of epileptic children taking antiepileptic drugs (AEDs). Patients demographic data and the free throxine (fT4) and thyroid-stimulating hormone (TSH) levels at the beginning of the treatment and at the third, sixth and ninth months of AED treatment were recorded retrospectively. A total of 106 children, 59 males and 47 females, were enrolled in the study. Mean patient age was 3.7 years, ranging between 3 months and 14 years. In total, 54% of patients were on valproic acid (VPA), 16% phenobarbital (PB), 14% were on carbamazepine (CBZ), 6% were on oxcarbazepine (OXC), 5% were on levetiracetam, and 5% were on topiramate therapy. There were no significant differences in average fT4 values between the drug groups. But the mean fT4 levels of the patients on VPA therapy showed a clear decrease within the observation period. No significant difference in average TSH values between the groups was detected in the beginning and in the third and sixth month. However, in the ninth month, a significant increase in TSH values was found in the VPA group (p = 0.007). In the patients taking VPA, average TSH values rose progressively while staying within normal limits. During follow-up, thyroid dysfunction were found in 21 patients (19.6%). A statistically significant relationship was found between severe electroencephalography (EEG) findings and thyroid dysfunction (p = 0.041). It was concluded that epileptic children with severe EEG findings and using VPA could have thyroid dysfunction. These patients should be followed up closely by thyroid function tests during treatment.

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin

OBJECTIVE:To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C.INTRODUCTION:Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis.METHODS:We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy.RESULTS:Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns.DISCUSSION:Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis.CONCLUSION:Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation, including the analysis of the free T4, TSH, and antithyroid antibody levels, should be mandatory before therapy, and an early re-evaluation within three months of treatment is necessary as an appropriate follow-up.

Interaction study with rats given two flame retardants: polybrominated diphenyl ethers (Bromkal 70‐5 DE) and chlorinated paraffins (Cereclor 70L)

AbstractThis study explored possible interaction effects on animal liver microsomal enzymes and thyroid hormones of two flame retardants: Bromkal 70‐5 DE, a mixture of polybrominated diphenyl ethers (hereafter called PBDE); and Cereclor 70L, a mixture of chlorinated paraffins (hereafter called CP).Female Sprague‐Dawley rats were exposed to these compounds in dose ranges of 1.3–18.7 mg/kg bw/day (PBDE) and 1–55 mg/kg bw/day (CP), by gavage for 14 days. Biological responses were measured on liver somatic index (LSI) and hepatic enzyme activity of (a) ethoxyresorufin‐O‐deethylase (EROD) (indicating CYP1A1 activity), (b) pentoxyresorufin‐O‐depentylase (PROD) (indicating CYP2B activity) and (c) the phase II conjugation enzyme uridine diphosphoglucuronosyl transferase (UDP‐GT). The levels of total and free thyroxine hormone in rat plasma (TT4 and FT4, respectively) were also measured. In the experimental work, a Doehlert uniform shell design was used in order to select the combination of concentrations of PBDE and CP administered to the rats. Eight different combinations were used, including a control. The measured responses were modelled with multiple linear regression (MLR), giving response surface plots. The results showed strong synergism between the two flame retardants at one particular exposure combination, resulting in increased hepatic microsomal enzyme responses and decreased serum T4 concentrations. Notably, the exposure combination causing the most marked effects represented intermediate doses of both substances. The mechanisms behind the observed effects are unknown, but may involve induction or inhibition of enzyme systems. Copyright © 2010 John Wiley &amp; Sons, Ltd.

Paternal genetic contribution influences fetal vulnerability to maternal alcohol consumption in a rat model of fetal alcohol spectrum disorder.

BackgroundFetal alcohol exposure causes in the offspring a collection of permanent physiological and neuropsychological deficits collectively termed Fetal Alcohol Spectrum Disorder (FASD). The timing and amount of exposure cannot fully explain the substantial variability among affected individuals, pointing to genetic influences that mediate fetal vulnerability. However, the aspects of vulnerability that depend on the mother, the father, or both, are not known.Methodology/Principal FindingsUsing the outbred Sprague-Dawley (SD) and inbred Brown Norway (BN) rat strains as well as their reciprocal crosses, we administered ethanol (E), pair-fed (PF), or control (C) diets to the pregnant dams. The dams' plasma levels of free thyroxine (fT4), triiodothyronine (T3), free T3 (fT3), and thyroid stimulating hormone (TSH) were measured to elucidate potential differences in maternal thyroid hormonal environment, which affects specific aspects of FASD. We then compared alcohol-exposed, pair fed, and control offspring of each fetal strain on gestational day 21 (G21) to identify maternal and paternal genetic effects on bodyweight and placental weight of male and female fetuses.ConclusionsSD and BN dams exhibited different baseline hypothalamic-pituitary-thyroid function. Moreover, the thyroid function of SD dams was more severely affected by alcohol consumption while that of BN dams was relatively resistant. This novel finding suggests that genetic differences in maternal thyroid function are one source of maternal genetic effects on fetal vulnerability to FASD. The fetal vulnerability to decreased bodyweight after alcohol exposure depended on the genetic contribution of both parents, not only maternal contribution as previously thought. In contrast, the effect of maternal alcohol consumption on placental weight was consistent and not strain-dependent. Interestingly, placental weight in fetuses with different paternal genetic contributions exhibited opposite responses to caloric restriction (pair feeding). In summary, these novel findings demonstrate both maternal and paternal genetic contributions to in utero vulnerability to alcohol, refining our understanding of the genetically-based heterogeneity seen in human FASD.

Factors Influencing Peripheral Conversion of Thyroxine to Tri-Iodothyronine in Athyreotic Individuals during Levothyroxine Replacement

Background: Tri-iodothyronine (T3) is the main active hormone, and 20% of this is derived from the thyroid gland and 80% is from the peripheral tissue according to 5'-monodeiodination of thyroxine (T4). In the previous studies, normal T3 levels were achieved with traditional levothyroxine (LT4) therapy alone in athyreotic patients, but there has been no data about the factors influencing peripheral conversion of LT4. The aim of this study was to determine the factor(s) influencing peripheral conversion of LT4 to T3 in athyreotic patients during LT4 replacement. Methods: The patients who underwent total-thyroidectomy for any cause, and mostly for thyroid cancers, at Asan Medical Center between 2000 and 2008 were enrolled. The free T4, T3 and thyroid stimulating hormone (TSH) levels and age, gender, weight, height, body mass index (BMI) and the T4 dose were measured. Only patients with normal ranges of free T4 and TSH were included in the analysis. Results: A total of 143 patients were enrolled. The mean T3, free T4 and TSH levels were 143.7 ng/dL, 1.4 ng/dL and 1.6 /mL, respectively. The mean weight and BMI were 62.9 kg and 24.6 kg/, respectively. We divided them into two groups according to the serum T3 level and we compared the characteristics of the groups. There were no differences in age, the gender distribution, the T4 dose/weight and the BMI between the low T3 group (T3 122 ng/dL, n = 14) and the normal T3 group (T3 > 122 ng/dL, n = 129). In the low T3 group, the mean body weight was significantly lower than that of the normal T3 group ( vs. , respectively, P = 0.025). Conclusion: Lean body mass seems to be an important factor for determining the peripheral conversion of T4 to T3 in human. This suggest that a combination of T3/T4 is better than T4 only when we treat the patients with hypothyroidism and who have a negligible amount of functioning thyroid tissue, if they have a low lean body mass.

Clinical Reasoning: An unusual case of papilledema after orthotopic liver transplantation

A 59-year-old, right-handed woman presented with a 7-day history of insidious onset of progressive blurring of vision of the right eye. She had undergone orthotopic liver transplantation 15 months previously due to non-A non-B fulminant hepatic failure. Her postoperative period was complicated by 2 episodes of acute rejection which responded to methylprednisolone, daclizumab, and change of immunosuppressive therapy from tacrolimus to cyclosporine. Three months prior she had developed nonspecific symptoms of weight loss, malaise, and anorexia. On examination she was alert and oriented. Visual acuity was 6/60 on the right and 6/36 on the left. Color vision was impaired bilaterally as tested with the Ishihara pseudoisochromatic plates. There was enlargement of both blind spots and severe constriction of fields with relative preservation of inferior nasal fields only. Ophthalmoscopic examination and fluorescein angiography showed bilateral pale swollen optic discs with peripapillary hemorrhages and venous engorgement (figure). The remaining neurologic examination was normal. Figure Photographs of the optic disc of the right and left eyes, showing bilateral pale swollen discs with flame-shaped hemorrhages and venous engorgement of the vessels ### Questions for consideration: 1. What are the possible differential diagnoses? 2. Which initial investigations would you recommend? The initial differential diagnosis for optic neuropathies with disc swelling included raised intracranial pressure, malignant hypertension, bilateral compressive thyroid ophthalmopathy, bilateral optic nerve tumors, bilateral simultaneous anterior ischemic optic neuropathy, idiopathic intracranial hypertension, and infective and inflammatory conditions. Twenty-four–hour ambulatory blood pressure monitoring was normal. Free thyroxin and thyroid stimulating hormone levels were normal. Thyroid antibodies were negative. Inflammatory markers were normal. Gadolinium-enhanced MRI of brain, orbits, pituitary, and optic nerves revealed increased signal uptake in the left optic nerve only, excluding …

Clinical Reasoning: Blurred vision and dancing feet

A 58-year-old woman presented to a neuro-ophthalmologist with a 5-year history of progressively blurred vision, diplopia, and longstanding bilateral ptosis. She described occasional choking episodes after eating as well as fatigue and shortness of breath after minimal exertion. Her older sibling had received corrective eyelid surgery for ptosis and two nieces had ptosis and proximal myopathy and were being investigated in another center. Direct and consensual pupillary light reflexes were normal with no rapid alternating pupillary defect. Visual acuity was 20/20 on the right and 20/30 on the left. She had bilateral symmetric ptosis obscuring two-thirds of the pupil and restriction of eye movements below 60% of normal in all directions of gaze. Lower limb examination revealed symmetric proximal limb weakness (Medical Research Council grade 4+) with reduced reflexes and flexor plantars. Tandem gait was hesitant. ### Questions for consideration: 1. What are the possible diagnoses? 2. What initial investigations would you recommend? The initial differential diagnosis included Graves thyroid eye disease, a neuromuscular junction disorder (myasthenia gravis or botulism), oculopharyngeal muscular dystrophy, Miller Fisher variant of Guillain-Barre syndrome, and progressive muscular dystrophy. Free thyroxin and thyroid stimulating hormone levels were normal. Thyroid antibodies were negative. Acetylcholine receptor antibody assay was negative and repetitive nerve stimulation to exclude a neuromuscular junction disorder was normal. Electromyography of proximal upper limb muscles revealed an increased number of short duration motor units consistent with borderline myopathy. Nerve conduction velocities were …

The Effect of Hormone Replacement Treatment on Thrombin-Activatable Fibrinolysis Inhibitor Activity Levels in Patients with Hashimoto Thyroiditis

Hypothyroid patients have increased risk of cardiovascular diseases, and several mechanisms have been considered responsible in these patients. Although, a few studies demonstrated fibrinolytic system changes in hypothyroid patients, there is no study demonstrating TAFI activity in hypothyroid Hashimoto's thyroiditis patients. The aim of this study was to evaluate TAFI activity status and the effect of L thyroxin hormone replacement treatment on fibrinolytic system in this patient group. Thirty patients with hypothyroid Hashimoto thyroiditis (all were female and the mean age was 44.3+/-14.6 years, ranging between 17-68 years) were enrolled to study. Their TSH levels were high (27.2+/-5.2 mU/L) and Free T3 and Free T4 hormone levels were below than normal. In this study, euthyroid 20 healthy volunteers (mean age 32.5+/-4.9 years, range 26-42 years) were adopted. L-thyroxin treatment before and after TAFI activity levels were measured in patients. In the control group, TAFI activity levels were 9.6+/-0.4 microg/mL. In patients with L-thyroxin before and after treatment there were high levels of TAFI activity value of 14.2+/-0.9 and 12.9+/-0.8 microg/mL, respectively. In the patient group, after L-thyroxin treatment TAFI activity levels were decreased but they were not statistically significant (p=0.187). When compared to the control group, high levels of TAFI activity were observed in the patient group (p<0.0001). Our data demonstrated that in Hashimoto thyroiditis, patients have high levels of TAFI activity compared to controls. A high level of TAFI activity suggests fibrinolytic deficit or thrombotic tendency in hypothyroid patients and this deficit is persistent after L-thyroxine replacement.

Hypothyroxinemia and effectiveness of thyroxin supplementation in very low birth weight infants with abdominal distension and poor weight gain

Background Very low birth weight (VLBW) infants sometimes develop abdominal distension and poor weight gain. The influence of thyroid function on these symptoms in VLBW infants has not been reported. Methods In a retrospective study, 18 VLBW infants whose abdominal distension and poor weight gain did not improve with standard treatment were enrolled as subjects. Serum levels of free thyroxin (fT 4) and thyroid stimulating hormone (TSH) were measured. Subjects with serum fT 4 levels less than 1.3 ng/dl received thyroxin supplementation. Another 18 VLBW infants were recruited as age- and weight-matched controls. We compared degree of intestinal dilation on X-ray, weight gain, and quantity of milk tolerated before and after starting thyroxin supplementation in the subjects and the controls. Results All subjects had serum fT 4 levels less than 1.3 ng/dl (mean, 0.72 ng/dl). TSH values varied widely and were less than 8 µU/ml in 12 subjects. Therefore, all subjects received thyroxin supplementation; after starting this, mean serum fT 4 level increased significantly to 1.31 ng/dl. In parallel with fT 4 increase, intestinal dilation improved in 16 of 18 subjects (mean grade of dilation decreased from 2.8 to 1.6). Weight gain and quantity of tolerated milk were significantly increased with thyroxin supplementation in all and 17 of the 18 subjects, respectively. Conclusions Thyroxin supplementation was effective in improving abdominal symptoms in VLBW infants whose serum fT 4 level was less than 1.3 ng/dl.

Endocrine Factors in Stress and Psychiatric Disorders

Glucocorticoids and other steroids produced in the adrenal cortex are altered in chronic stress situations associated with enhanced anxiety. A useful tool to evaluate changes in adrenal steroids during stress and anxiety under both laboratory and real-life stress situations is determination of steroids in saliva. The main advantages of this technique are its noninvasiveness and its measurement of biologically active free hormone levels. Salivary cortisol is a valuable indicator of the activity of the hypothalamic-pituitary-adrenocortical axis, which is known to be altered in psychiatric disorders. Measurements of salivary cortisol helped to reveal changes that would otherwise remained undetected, such as increase in cortisol release in spontaneously occurring panic attacks. By selecting only the subjects with high and low trait anxiety, we have brought evidence confirmed by others that high trait anxiety may be associated with an inability to respond with adequate cortisol release during stress. Papers on the relationship between salivary dehydroepiandrosterone and trait anxiety or anxiety disorders are rare, and this stress hormone deserves more attention. Almost nothing is known on aldosterone and anxiety. We have modified the methodology of aldosterone radioimmunoassay by concentrating the saliva and validated it biologically by demonstrating daily variation and gender differences. We have provided the first data on the relationship between aldosterone and trait anxiety. Obtained results show a significant negative correlation between morning salivary aldosterone concentrations and trait anxiety scores in women (luteal phase), but not in men. A more proper elucidation of the association between aldosterone and anxiety seems to be an important target of further research.

Hypothyroidism and High Plasma and Urine Iodine Levels Related to the Use of Gastrografin

We report the effect of Gastrografin on thyroid function in 7 neonates. Levels of free thyroxine and thyroid stimulating hormone, serum and urine iodine concentrations were determined before and after using gastrografin. Transient hypothyroidism was seen in 3 patients. No thyroid gland dysfunction was detected in the Neonatal Screening Program for congenital hypothyroidism before the administration of Gastrografin and thyroid antibodies were negative. Urine and serum iodine concentrations were elevated after Gastrografin administration. Normal thyroid hormone concentrations were observed in the other four infants. We suggest careful evaluation of thyroid function whenever Gastrografin is used. Keywords: Thyroid hormones, TSH, thyroxine, newborn, iodinated contrast media

Serum free T4 and thyroid stimulating hormone levels in preterm infants and relationship between these levels and respiratory distress syndrome

There have been few studies of the thyroid stimulating hormone (TSH) surge in extremely low-birthweight (ELBW) infants, and the relationship between thyroid hormones and respiratory distress syndrome (RDS) has yet to be clarified. The present study sought to determine the serum levels of free T4 (fT4) and TSH in ELBW infants and to examine the relationship between these levels and the development of RDS. The authors measured serum fT4 and TSH levels soon after birth in 449 preterm infants, who were born at 22-36 weeks of gestation, and determined the associations between these levels, the incidence of RDS, and the recognized clinical factors associated with RDS. Serum fT4 and TSH levels, and the fT4/TSH ratio, in the group at 22-24 weeks of gestation were significantly lower than those in the group at 28-36 weeks. The levels and ratio increased significantly with increasing gestational age. There were significant correlations between the serum fT4 level and the birthweight, Apgar score, and gender, and between the serum TSH level and the gestational age, mode of delivery, and birthweight. No significant relationship between the incidence of RDS and the serum levels of fT4 and TSH was observed. The authors' results suggest that the serum levels of fT4 and TSH in ELBW infants are very low, and that these levels are not correlated with the occurrence of RDS.

Hyporesponsiveness to Glucocorticoids in Mice Genetically Deficient for the Corticosteroid Binding Globulin

Corticosteroid binding globulin (CBG) is the carrier for glucocorticoids in plasma. The protein is believed to keep the steroids inactive and to regulate the amount of free hormone acting on target tissues (free hormone hypothesis). Here, we generated a mouse model genetically deficient for CBG to test the contribution of the carrier to glucocorticoid action and adrenocortical stress response. The absence of CBG resulted in a lack of corticosterone binding activity in serum and in an approximately 10-fold increase in free corticosterone levels in CBG-null mice, consistent with its role in regulation of circulating free hormone levels. Surprisingly, cbg(-/-) animals did not exhibit features seen in organisms with enhanced glucocorticoid signaling. Rather, the mice exhibited increased activity of the pituitary axis of hormonal control, normal levels of gluconeogenetic enzymes, and fatigue, as well as an aggravated response to septic shock, indicating an inability to appropriately respond to the excess free corticosterone in the absence of CBG. Thus, our data suggest an active role for CBG in bioavailability, local delivery, and/or cellular signal transduction of glucocorticoids that extends beyond a function as a mere cargo transporter.

Size breeds success: multiple paternity, multivariate selection and male semelparity in a small marsupial, Antechinus stuartii

Mating in the marsupial genus Antechinus is a synchronous annual event that is characterized by monoestry in females and abrupt postmating mortality in males. Male semelparity (multiple copulations during a single breeding season per lifetime) is often assumed to occur as a consequence of the intense mating effort expended by males in the rut, but the forces selecting for this remain elusive. Here, we investigate selection in male brown antechinus, Antechinus stuartii, and test two hypotheses for the evolution of semelparity: intermale competition and sperm competition. If intermale competition drives semelparity, we predicted that males would be under strong selection for large body size. If sperm competition is important, we predicted that selection would be strongest on scrotal size, a surrogate for testes volume. Using microsatellite markers, we found that 92% of females in free-living conditions mated with multiple males, producing litters of eight that had up to four fathers. These observations confirm the potential for sperm competition. Using selection analysis, we then found paternity success in 119 males to be related most strongly to body mass and scrotal size, thus providing support for both hypotheses. Large males presumably experience increased paternity success by gaining more matings or prolonged copulations via mate guarding, while large testes may allow increased sperm investment per copulation. Increased levels of free corticosteroid hormones in males facilitate the extreme mating effort during the short period of rut, but lead to immune suppression and consequently to the phenomenon of postmating mortality.

Effets métaboliques et endocriniens de la privation hydrique et/ou alimentaire chez le rat

We aim at studying the effect of water deprivation, food deprivation and their combination for three days on adrenal cortex, pituitary-thyroid axis and vasopressinergic system activity in rats. Corticosterone level was determined by fluorimetric method. The levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH) were determined by immunoenzymatic assay and vasopressin (AVP) level was determined by radio-immunoassay. In all three groups, basal levels of plasma corticosterone were increased. A thyroid dysfunction was shown after water deprivation, food deprivation and their combination reflected by a significant decrease in FT4 levels. Paradoxically, a significant decrease in TSH level was observed in food-deprived rats and in rats subjected to simultaneous food and water deprivation, while a slight and not significant decrease in TSH level was shown in water-deprived rats. A significant increase in plasma AVP level was observed after water deprivation and simultaneous water and food deprivation, while no change was found after food deprivation. The data indicated that water deprivation, food deprivation and their combination stimulated the adrenal cortex, thereby suggesting a stress state. On the other hand, it seems that nutritional stress modifies the pituitary-thyroid axis through mechanisms different from those of osmotic stress. Moreover, it seems that food deprivation partially prevented the stimulatory effect of water deprivation on vasopressinergic system. To cite this article: A.G. Kasdallah et al., C. R. Biologies 328 (2005).

The Effects of Hormones of the Hypothalamo-Hypophyseal-Adrenal, Renin-Angiotensin, and Thyroid Hormone Systems on the Formation of Dyscirculatory Encephalopathy

Measurements were made of plasma levels of free (f) thyroxine (fT4), triiodothyronine (fT3), thyrotropic hormone (TSH), adrenocorticotrophic hormone (ACTH), aldosterone, and renin in patients with dyscirculatory encephalopathy (DE). Their influences on the development of chronic circulatory insufficiency were assessed. A total of 39 patients were studied (aged 45-73 years) with DE stages I and II, without acute or chronic (in the exacerbation phase) somatic illness. These observations showed that diffuse lesions of brain tissues of different severities were accompanied by the following changes in thyroid homeostasis: 1) significant combined increases in TSH without alteration to the "fT3-TSH" negative feedback regulatory mechanism in patients with stage I DE; 2) significant combined decreases in TSH levels with marked suppression of the conversion of thyroxine into triiodothyronine and an interaction with impairments in the "fT3-hypophysis" system in patients with stage II DE. In addition, there were changes (increases) in cortisol levels with simultaneous decreases in renin levels in patients with stage II DE as compared with patients with stage I DE. Correlation analysis demonstrated the absence of any relationship between the age of the patients, the state of hormonal homeostasis, and the extent of vascular stenosis. These results suggest a role for hormones of the hypothalamo-hypophyseal-adrenal, thyroid, and renin-angiotensin systems in the mechanism by which DE develops as well as the possibility of using tests for these hormones as additional criteria for assessing the severity of diffuse brain lesions.