Unusual features of neonatal thyroid function in small-for-gestational-age lambs. Origin of plasma T4 and T3 deficiencies

Thyroid function was studied in small for gestational age (SGA) or control newborn lambs. Neonatal changes in plasma concentrations of TSH, T3, rT3, total and free T4 were monitored, and thyroid scintigraphs were performed. Responsiveness of the hypothalamic-pituitary-thyroid axis to cold exposure and TRH or TSH administration was assessed. In addition, T4 and T3 kinetic studies were performed. In agreement with results obtained in babies, plasma T3, total T4 and free T4 concentrations were depressed in low birth weight animals, whereas TSH and rT3 levels were not affected. Thyroid size expressed relatively to the body weight was higher in SGA animals, thus suggesting that a partial compensation for low thyroid hormone levels had occurred during the fetal life. Plasma TSH and T4 concentrations increased by a same extent after exposure to cold and TRH or TSH administration in SGA and control lambs; however, the rise in T3 levels was depressed in the former in all stimulation tests. T3 and T4 production rates were similar in the two experimental groups. In SGA lambs, the metabolic clearance rate and the total distribution space of these two hormones were significantly increased; the fast T3 pool was higher, and the slow T3 pool lower than in control animals. All these results demonstrate that, despite low circulating thyroid hormone concentrations, SGA lambs are not hypothyroid. An increased T4 and T3 storage in the extravascular compartment is probably the major factor involved in the occurrence of this plasma deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)     

The pituitary-thyroid axis in patients with pituitary disorders

The pituitary-thyroid axis of 12 patients, exposed to transsphenoidal pituitary microsurgery because of nonfunctioning adenomas (6), prolactinomas (3) and craniopharyngioma (1), or to major pituitary injury (1 apoplexy, 1 accidental injury), was controlled more than 6 months following the incidents. The patients did not receive thyroid replacement therapy and were evaluated by measurement of the serum concentration of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), T3-resin uptake test and thyrotropin (TSH, IRMA method) before and after 200 micrograms thyrotropin releasing hormone (TRH) iv. The examination also included measurement of prolactin (PRL) and cortisol (C) in serum. Apart from 1 patient with pituitary apoplexy all had normal basal TSH levels and 9 showed a significant TSH response to TRH. Compared to 40 normal control subjects the 12 patients had significantly decreased levels of T4, T3 and rT3 (expressed in free indices), while the TSH levels showed no change. Five of the patients, studied before and following surgery, had all decreased and subnormal FT4I (free T4 index) after surgery, but unchanged FT3I and TSH. The levels of FT4I were positively correlated to both those of FT3I and FrT3I, but not to TSH. The TSH and thyroid hormone values showed no relationship to the levels of PRL or C of the patients exposed to surgery. It is concluded that the risk of hypothyroidism in patients exposed to pituitary microsurgery is not appearing from the TSH response to TRH, but from the thyroid hormone levels.     

Maturation of the pituitary-thyroid axis during the perinatal period.

To clarify the maturation process of the pituitary-thyroid axis during the perinatal period, thyrotropin (TSH) response to thyrotropin releasing hormone (TRH) and serum thyroid hormone levels were examined in 26 healthy infants of 30 to 40 weeks gestation. A TRH stimulation test was performed on 10 to 20 postnatal days. Basal concentrations of serum thyroxine (T4), free thyroxine (free T4) and triiodothyronine (T3) were positively correlated to gestational age and birth weight (p less than 0.001-0.01). Seven infants of 30 to 35 gestational weeks demonstrated an exaggerated TSH response to TRH (49.7 +/- 6.7 microU/ml versus 22.1 +/- 4.8 microU/ml, p less than 0.001), which was gradually reduced with gestational age and normalized after 37 weeks gestation. A similar decrease in TSH responsiveness to TRH was also observed longitudinally in all of 5 high responders repeatedly examined. There was a negative correlation between basal or peak TSH concentrations and postconceptional age in high responders (r = -0.59 p less than 0.05, r = -0.66 p less than 0.01), whereas in the normal responders TSH response, remained at a constant level during 31 to 43 postconceptional weeks. On the other hand, there was no correlation between basal or peak TSH levels and serum thyroid hormones. These results indicate that (1) maturation of the pituitary-thyroid axis is intrinsically controlled by gestational age rather than by serum thyroid hormone levels, (2) hypersecretion of TSH in preterm infants induces a progressive increase in serum thyroid hormones, and (3) although there is individual variation in the maturation process, the feedback regulation of the pituitary-thyroid axis matures by approximately the 37th gestational week.     

Acute and transient activation of pituitary-thyroid axis during unforced restriction in rats: component of nonshivering thermogenesis in conscious animals?

Groups of 6-8 male Wistar Olac SPF rats weighing about 300 g were subjected to unforced restriction (UR) in small cages with a metallic bottom and a Plexiglas cover for various intervals from 2 min to 72 h. An acute activation of the pituitary-thyroid axis was found which was manifested by an increase of thyrotropin (TSH) and thyroxine (T4) levels at 2-5 min of UR. This was presumably due to the emotional effect of a rapid transfer and to the placing of the animals into restriction cages. Later, between 3 and 6 h of UR, another, and more pronounced period of activation of the pituitary-thyroid axis and of the peripheral thyroid hormone metabolism was repeatedly observed which lasted until about 36-48 h and was manifested by a highly significant increase of TSH, T4, 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) levels. It was concluded that this phenomenon presumably may be a component of nonshivering thermogenesis resulting from a decreased muscular activity and resembling the conditions occurring under cold stress. Such a view was supported by findings of highly increased nonesterified fatty acid levels in plasma in restricted animals, by unchanged levels of TSH and thyroid hormones found in unrestricted animals kept individually in regular group cages and, finally, by a preventive effect of ambient temperature of 32 degrees C on the pituitary-thyroid activation at 6 h of UR. In some experiments, no substantial differences in hormone levels were found between the animals kept in Plexiglas or stainless wire-mesh restriction cages. Finally, a multifold increase of prolactin level in plasma was found as early as 2 min of UR, the peak being observed between 5 and 20 min and a decrease to about the initial level at about 360 min.     

Thyrotropic and peripheral activities of thyrotrophin and thyrotrophin-releasing hormone in the chick embryo and adult chicken

The influence of an intravenous injection of thyrotrophin-releasing hormone (TRH) and bovine thyrotrophin (TSH) on circulating levels of thyroid hormones and the liver 5'-monodeiodination (5'-D) activity is studied in the chick embryo and the adult chicken. In the 18-day-old chick embryo, an injection of 1 microgram TRH and 0.01 I.U. TSH increase plasma concentrations of triiodothyronine (T3) and of thyroxine (T4). TRH, however, preferentially raises plasma levels of T3, resulting in an increased T3 to T4 ratio, whereas TSH preferentially increases T4, resulting in a decreased T3 to T4 ratio. The 5'-D-activity is also stimulated following TRH but not following TSH administration. The increase of reverse T3 (rT3) is much more pronounced following the administration of TSH. In adult chicken an injection of up to 20 micrograms of TRH never increased plasma concentrations of T4, but increases T3 at every dose used together with 5'-D at the 20 micrograms dose. TSH on the other hand never increased T3 or 5'-D, but elevates T4 consistently. It is concluded that TSH is mainly thyrotropic in the chick embryo or adult chicken whereas TRH is responsible for the peripheral conversion of T4 into T3 by stimulating the 5'-D-activity. The involvement of a TRH induced GH release in this peripheral activity is discussed.     

TRH test in patients with diabetes mellitus type 1 and/or autoimmune thyroiditis. Changes in the pituitary-thyroid axis, reverse T3, prolactin and growth hormone levels

The response of the pituitary- thyroid axis, reverse triiodothyronine (rT3), prolactin, and growth hormone (GH) levels following TRH stimulus (Relefact TRH 200 microg 2 amp. i.v.) was examined in patients with autoimmune diabetes type 1 (DM1, n=30), with autoimmune thyroiditis (AT, n=25), and with concurrent DM1 and AT (n=22) to evaluate the influence of DM1 and AT of autoimmune pathogenesis on the above-mentioned hormonal parameters. Statistical analysis (ANOVA) showed that: a) the response of TSH did not differ from control groups (C); b) free triiodothyronine (fT3), free thyroxine (fT4) and their ratio in DM1, DM1+AT and C rose in 120 and 180 min, while a similar increase was not seen in AT (p<0.000001); c) rT3 was not present in any group, with rT3 levels higher in AT (p<0.00002) and lower in DM1 (p<0.02); d) the response of GH had a paradoxical character in some patients in all groups, most often in DM1 (52 %, DM1 vs C, p <0.01). The characteristic response difference was not in the peak GH level, but the delayed return to basal levels in DM1 (p<0.0001) and an abrupt one in AT (p<0.0001). The major findings in DM1 were the differences in GH response, while significant impairment of pituitary-thyroid axis and PRL response to TRH was absent. AT was associated with impairment of TRH stimulated fT3, fT4, fT3/fT4 response and changes in rT3 levels, in spite of preserved TRH-stimulated TSH secretion. GH response in AT patients was also altered.     

Changes in the hypothalamic-pituitary-thyroid axis during acute starvation in non-obese patients

We investigated changes in the hypothalamic-pituitary-thyroid axis before, during, and after fasting in twenty-one non-obese euthyroid patients with psychosomatic diseases. Blood samples for free T3 (FT3), T3, free T4 (FT4), T4, reverse T3 (rT3), and TSH were obtained from all patients before and on the 5th day of fasting, and in 11 of the same individuals on the 5th day of refeeding. Serum TSH and T3 responses to TRH were also evaluated in 10 patients before and on the 5th day of fasting. During the fast, FT3, T3 and TSH levels decreased significantly and rT3 levels increased significantly whereas FT4 and T4 levels remained within the normal range. Maximal delta TSH, peak TSH levels, max delta T3, peak T3 levels, and net secretory responses to TRH decreased significantly. Peak TSH levels and max delta TSH to TRH correlated well with basal levels of TSH. A statistically significant negative correlation between basal levels of FT4 and TSH was observed. After refeeding, there was a significant increase only in TSH which returned to prefasting values. These results demonstrated that in a state of "low T3" during acute starvation a reduction in serum T3 might depend partly on TSH-mediated thyroidal secretion.     

Effects of exposure of pregnant rats to TRH on development of the pituitary-thyroid axis in their progeny

TRH (10 and 1000 micrograms/kg body weight (BW] was injected ip into pregnant rats daily from day 0 to 20 of pregnancy, and the pituitary-thyroid axis of their pups (Mat-TRH rats) was examined on days 0, 4, 10, 21 and 90 after birth. The pituitary TSH content of male Mat-TRH rats was significantly lower on day 4, and higher on day 10 than that of control rats. The serum TSH was significantly higher on day 10 (except female 10 micrograms/kg group). An exaggerated TSH response to exogenous TRH (10 micrograms/kg BW; ip) was observed on day 10 (males, 1000 micrograms/kg group). The serum T4 level of female Mat-TRH rats was low on day 4 (1000 micrograms/kg group), and higher on day 10. On days 21 and 90, the levels of pituitary TSH, serum TSH and T4 in Mat-TRH rats were similar to those in controls, but the TSH response to TRH was still exaggerated (1000 micrograms/kg group). No significant difference between control and TRH-treated mothers was seen on days 10 and 90 postpartum except for a decreased pituitary TSH content on day 10 in the 1000 micrograms/kg group. It is concluded that repeated administration of TRH to pregnant rats shows an effect on the pituitary-thyroid axis function of their progeny in later life.     

Circulating LH, FSH, prolactin, testosterone, delta 4-androstenedione, dehydroepiandrosterone sulfate and cortisol levels in the fetus in late gestation and in newborn male and female lambs

Gonadotropins, prolactin (PRL), testosterone (T), delta 4-androstenedione, dehydroepiandrosterone sulfate and cortisol (F) levels were determined from 14 days before birth to term in 3 female and 3 male ovine fetuses with a chronically implanted venous catheter, and in the same animals from birth to 72 h of age. In both sexes, plasma gonadotropins and androgens were low throughout the period of study while plasma F increased with gestational age. After birth, plasma gonadotropins and PRL tended to increase progressively with time while PRL concentrations were significantly higher in female than in male lambs. F and T concentrations decreased significantly within the first 12 and 6 h of postnatal life. Higher T values were again observed at 36 h in male lambs. These data indicate that the fetal hypothalamic-pituitary-gonadal axis is relatively quiescent in the last 14 days of gestation but is activated within the first 72 h after birth.     

Long-term intramuscular administration of thyrotropin-releasing hormone tartrate in patients with cerebrovascular disease: effects on the pituitary-thyroid axis.

We studied the effects of long-term (30 days) refracted daily intramuscular administration of 4 mg TRH tartrate (TRH-T) on the pituitary-thyroid axis in 20 euthyroid patients affected by cerebrovascular disease (CVD). All subjects were assayed for T4, T3, FT4, FT3, TSH and TBG plasma levels before treatment (D0), after 15 and 30 treatment days (D15, D30), and after a 15-day washout (D45). In addition, TSH response to 200 micrograms intravenous TRH was assessed at D0, D30 and D45. We observed a significant increase in T4, FT4 and FT3 levels in the face of decreased TSH concentrations. A blunted TSH response to TRH bolus persisted at D30. These data demonstrate that the down-regulation mechanism may be partially overcome in vivo when thyrotrophs are chronically exposed to pharmacological TRH-T doses and that TSH pattern is mainly due to the negative feedback of thyroid hormones, even though pituitary TSH reserves may become depleted. Furthermore, prolonged TRH-T administration does not produce hyperthyroidism in euthyroid CVD patients.     

Effects of streptozotocin-induced diabetes mellitus on hypothalamic-pituitary-thyroid axis in rats

The effects of streptozotocin-induced diabetes mellitus on the hypothalamic-pituitary-thyroid axis in rats were studied. Streptozotocin (60 mg/kg) was injected ip. Rats were decapitated at two and four weeks after the streptozotocin treatment. Thyrotropin releasing hormone (TRH), thyrotropin (TSH), thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) were measured by means of the specific radioimmunoassay for each. Immunoreactive TRH (ir-TRH) contents in the hypothalamus significantly decreased at four weeks (p less than 0.02). Basal TSH levels in plasma significantly decreased (p less than 0.005, p less than 0.001), and plasma ir-TRH and TSH responses to cold were significantly inhibited after the streptozotocin treatment (p less than 0.001). The plasma TSH response to TRH was decreased, but not significantly. The plasma T4 and T3 levels fell significantly. RT3 did not change throughout the experiment. 3,3'-T2 levels in plasma fell significantly, whereas 3',5'-T2 increased. Blood glucose levels rose significantly after streptozotocin treatment, but insulin treatment led to partial restoration. The findings suggest that streptozotocin-induced diabetes mellitus affects various sites of the hypothalamic-pituitary-thyroid axis in rats.     

Thyroid function tests in children with congenital hypothyroidism on L-thyroxine treatment

The plasma levels of thyroxine (T4), triiodothyronine (T3), free T4 (FT4), free T3 (FT3), reverse T3 (rT3) and immunoradiometrically assayed thyrotropin (IRMA TSH) have been measured in 28 L-T4-treated children with congenital hypothyroidism as well as in a control group (group C). The patients were subdivided into 2 groups according to the nonsuppressed (group A) or suppressed (group B) TSH response to TSH-releasing hormone (TRH). Basal IRMA TSH correlated with the TSH increment after TRH and it was significantly lower in group B vs. groups A and C, while no difference was present between groups A and B in regard to T4, FT4 and rT3, all higher than in group C. FT3 levels were similar in the 3 groups. In children, as in adults, basal IRMA TSH seems to be a reliable index in monitoring overtreatment.     

The pituitary-thyroid axis in acromegaly

The pituitary-thyroid axis of 12 acromegalic patients was evaluated by measurement of the serum concentrations (total and free) of thyroxine (T4), triiodothyronine (T3) and reverse T3 (rT3) and thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) before and after iv stimulation with thyrotropin releasing hormone (TRH). Using an ultrasensitive method of TSH measurement (IRMA) basal serum TSH levels of the patients (0.76, 0.07-1.90 mIU/l) were found slightly, but significantly (P less than 0.01), lower than in 40 healthy controls (1.40, 0.41-2.50 mIU/l). The total T4 levels (TT4) were also reduced (84, 69-106 nmol/l vs 100, 72-156 nmol/l, P less than 0.01) and significantly correlated (P less than 0.02, R = 0.69) to the TSH response to TRH, suggesting a slight central hypothyroidism. The acromegalics had, however, normal serum levels of TT3 (1.79, 1.23-2.52 nmol/l vs 1.74, 0.78-2.84 nmol/l, P greater than 0.10), but significantly decreased levels of TrT3 (0.173, 0.077-0.430 nmol/l vs 0.368, 0.154-0.584 nmol/l, P less than 0.01) compared to the controls. The serum concentration of the free iodothyronines (FT4, FT3, FrT3) showed similar differences between acromegalics and normal controls. All the acromegalics showed a rise of serum TSH, GH and PRL after TRH. Positive correlation (P less than 0.05, R = 0.59) was found between the TSH and GH responses, but not between these two parameters and the PRL response to TRH. These findings may be explained by the existence of a central suppression of the TSH and GH secretion in acromegalic subjects, possibly exerted by somatostatin. Euthyroidism might be maintained by an increased extrathyroidal conversion of T4 to T3.     

Pituitary-thyroid axis reactivity to hyper- and hypothyroidism in the perinatal period: ontogeny of regulation of regulation and long-term programming of responses.

To evaluate the role of perinatal thyroid status in the development of pituitary-thyroid axis regulation, we administered triiodothyronine to newborn rats for the first five days postpartum to achieve hyperthyroidism, or propylthiouracil perinatally to rat dams and pups from gestational day 17 through postnatal day 5 to achieve hypothyroidism. Plasma T4, T3, and TSH levels were determined from birth through 50 days postpartum. Administration of exogenous T3 produced the expected immediate suppression of plasma T4 and TSH, with recovery toward normal values beginning within days of discontinuing the T3 regimen. Plasma T3 values were markedly elevated during the period in which T3 was being given, but subsequently became subnormal, with deficits persisting into young adulthood. With the PTU regimen, plasma T4 and T3 levels were markedly suppressed through postnatal day 10, rose over the ensuing two weeks, but nevertheless showed significant deficits into adulthood. TSH levels in the immediate neonatal period were subnormal in the PTU group, despite the marked lowering of circulating thyroid hormones; TSH then rose dramatically to levels four times normal, subsiding to control values by the end of the first month. These results suggest that a critical period exists in which regulation of pituitary-thyroid axis function is programmed. During this phase, TSH secretion can be suppressed by excess thyroid hormones, but cannot be increased by hormone deficiencies. Perhaps more importantly, perinatal thyroid status "programs" its own future reactivity, so that early hypothyroidism results in reduced T4 and T3 levels in adulthood, despite normal levels of TSH.     

Effects of anticonvulsant monotherapy in pregnancy on the newborn endocrine system. Preliminary data

Pituitary-thyroid axis function and gonadotropin secretion were evaluated by a combined TRH and LHRH test in 4 newborn female infants appropriate for gestational age of mothers treated by AEDs throughout pregnancy. We found: high basal FSH levels with normal FSH reserve, normal LH-HCG levels both before and after LHRH stimulation, normal TSH and T4 levels both before and after TRH stimulation, high T3 basal values with a normal increase after TRH and low rT3 basal values. It is suggested an AED increased T4 deiodination towards T3 in the newborn liver without a marked impairment of the endocrine functions of the fetus.     

Significance of serum thyrotropin and plasma dopamine concentration in the regulation of thyroid function in elderly subjects

In our previous study, we observed a tendency towards an age-related increase in the serum thyrotropin (TSH) concentration. Regulatory mechanisms of TSH secretion in elderly subjects were studied. In 43 elderly subjects, serum TSH did not correlate significantly with serum T4, T3 free T4 or rT3. Further, those with increased TSH (greater than 5 mU/l, 9 subjects) did not overlap with those with low T3 (less than 0.92 nmol/1, 8 subjects). Increases in serum TSH were not associated with the presence of circulating anti-thyroid autoantibodies. A TRH test using a 500 micrograms single bolus injection was performed in 15 subjects. TSH response (basal: 1.92 +/- 1.42 (s.d.) mU/1, peak: 11.25 +/- 5.33 mU/1, sigma: 26.74 +/- 12.89 mU/1, respectively) did not differ significantly from that of younger subjects. T3 response after TRH varied greatly and a close correlation was observed between basal T3 and peak T3 (r = 0.86), and also between peak T3 and delta T3 (r = 0.81). A significant correlation was observed between sigma TSH and basal T3 (r = 0.60). Neither plasma cortisol, epinephrine nor norepinephrine concentrations showed any significant correlation with basal and TRH-stimulated TSH or T3 concentrations. However, the plasma dopamine concentration correlated significantly with sigma TSH (r = 0.60) and basal T3 (r = 0.52), respectively. In conclusion, the increase in serum TSH observed in elderly subjects was felt to represent a physiological adaptation to maintain serum T3. Low T3 subjects appear to have a disturbance in this mechanism, with decreased TSH and T3 response to TRH stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of methadone on TSH and thyroid hormone secretion

The hypothalamus-pituitary-thyroid function was studied in 15 male patients on chronic methadone treatment (40 mg/day). No significant variations of TSH, T4, T3 and rT3 levels were documented, either in basal conditions or after TRH stimulation; however a reduced TSH pituitary response was recorded in some patients (6 out of 15).     

Thyroid hormone regulation by stress and behavioral differences in adult male rats

Thyroid hormones are essential regulators of growth, development and normal bodily function and their release is coordinated by the hypothalamic-pituitary-thyroid (HPT) axis. While the HPT axis has been established as an acutely stress-responsive neuroendocrine system, relatively little is known about the mechanisms of its stress regulation. The present study examined acute stress-induced changes in peripheral hormone levels [triiodothyronine (T3); thyroxine (T4), thyroid-stimulating hormone (TSH), reverse triiodothyronine (rT3)] and central mRNA levels of regulators of the HPT axis [thyrotropin-releasing hormone (TRH), somatostatin (SST), type II deiodinase (D2)] in response to an inescapable tail-shock, a rodent model of stress. Additionally, we examined whether individual differences in spontaneous exploratory behavior in an open field test predicted basal levels of TH or differential susceptibility to the effects of stress. The stress condition was associated with decreases in peripheral T3, T4 and TSH, but not rT3, when compared with controls. No changes were observed in TRH or SST mRNA levels, but there was a trend suggesting stress-related increases in D2 mRNA. We also found that an animal's exploratory behavior in an unfamiliar open field arena was positively related to peripheral thyroid hormone levels and predicted the magnitude of stress-induced changes.In conclusion, we found suggestive evidence for stress-induced decrease in central drive HPT axis, but the central mechanisms of its stress regulation remain to be elucidated. Additionally, we found that individual differences in animals' exploratory behavior were correlated with peripheral TH levels.     

Chronic exposure to short photoperiod inhibits free thyroxine index and plasma levels of TSH, T4, triiodothyronine (T3) and cholesterol in female Syrian hamsters

1. Chronic exposure of female Syrian hamsters (Mesocricetus auratus) for 9 weeks to a short photoperiod (10L:14D) depressed the pituitary-thyroid axis as indicated by a drop in circulating titers of thyroid stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and the free thyroxine index (FT4I) compared to animals maintained under long photoperiodic conditions (14L:10D). 2. Short day treatment also reduced plasma cholesterol levels. 3. Neither plasma triglycerides, glucose nor growth hormone (GH) levels differed between hamsters exposed to short or long daily photoperiods.     

Thyroid function in the newborn lamb. Physiological approach of the mechanisms inducing the changes in plasma thyroxine, free thyroxine and triiodothyronine concentrations

Several experiments were performed to study the mechanisms inducing the neonatal rises in plasma iodothyronine concentrations in lambs. TSH levels rose during the first 4 to 8h of life, whereas plasma T4 an T3 concentrations increased only from birth to respectively 2 and 1h; the rise in free T4 levels was longer and more important than the rise in total T4. Only T4 changes were strongly related to the extent of TSH increase. The neonatal TSH surge was inhibited by delaying the first milk intake, indicating a great importance of the early nutritional status; in these conditions, the neonatal T4 rise did not occur, whereas the T3 increase was not affected; therefore, in contrast to T4, the T3 increase occurring at birth is not TSH-dependent. As in thyroidectomized lambs continuously infused with T4, plasma T3 concentrations did not increase at birth, it appears that the neonatal T3 surge probably has a thyroidal origin. These results raise the possibility of the existence of a specific stimulator of thyroidal T3 secretion, at least in the newborn lamb. In addition, comparison of the respective T4 increases, at birth or after TSH stimulation in 24 h-old animals, suggests that the ability of the thyroid to respond to a sustained stimulation is strongly reduced at birth. Lastly, neonatal changes in the affinity and/or capacity of carrier proteins for T4, perhaps partly induced by the observed simultaneous rise in free fatty acid levels, could explain that plasma T3 concentrations remained elevated despite a decrease in total T4 levels from 2 h after birth.