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.     

Effects of various drugs on thyrotropin secretion in rats

The effects of alpha-neoendorphin, kyotorphin, melatonin or diphenylhydantoin (DPH) on thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) release in rats were studied. alpha-neoendorphin (1.0 mg/kg), kyotorphin (1.0 mg/kg), melatonin (2.5 mg/kg) or DPH (75 mg/kg) was injected iv or ip, and the rats were serially decapitated. TRH, TSH and thyroid hormone were determined by radioimmunoassay. The hypothalamic immunoreactive (ir-TRH) contents decreased significantly after melatonin injection, but not after alpha-neoendorphin, kyotorphin or DPH. The plasma ir-TRH concentrations decreased significantly after DPH injection, but not after alpha-neoendorphin, kyotorphin or melatonin. The plasma TSH levels decreased significantly in a dose-related manner with a nadir at 10 min. after melatonin, at 30 min. after DPH and at 40 min. after alpha-neoendorphin or kyotorphin injection. The plasma thyroid hormone levels did not change significantly after these drugs injection. The plasma ir-TRH and TSH responses to cold were inhibited by these drugs, but the plasma TSH response to TRH was not influenced. In the L-DOPA- or 5-hydroxy-tryptophan (5-HTP)-pretreated group, the inhibitory effect of alpha-neoendorphin or kyotorphin on TSH levels was prevented, but not in the haloperidol- or para-chloprophenylalanine (PCPA)- pretreated group. In the haloperidol- or PCPA-pretreated group, the inhibitory effect of melatonin on TSH levels was prevented, but not in the L-DOPA- or 5-HTP-pretreated group. These drugs alone did not affect plasma TSH levels in terms of the dose used. The inactivation of TRH immunoreactivity by hypothalamus or plasma in vitro after these drugs injection did not differ from that of the control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of histamine and related compounds on thyrotropin secretion in rats

The effects of histamine (HA) and related compounds on thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) secretion in rats were studied. Histidine (1.0 g/kg), HA (5.0 mg/kg) or histamine antagonists mepyramine (MP) (100 mg/kg) or famotidine (FA) (5.0 mg/kg) were injected intraperitoneally, and the rats were decapitated at various intervals after the injection. The hypothalamic immunoreactive TRH (ir-TRH) content increased significantly after histidine or HA injection, decreased significantly after FA injection, but was not changed by MP. The plasma ir-TRH concentration did not change significantly after injection of these drugs. The plasma TSH levels decreased significantly in a dose-related manner after histidine or HA injection and increased significantly in a dose-related manner after FA injection. The plasma thyroid hormone levels showed no changes. In the FA-pretreated group, the inhibitory effect of histidine or HA on TSH levels was prevented, but not in the MP-pretreated group. The plasma ir-TRH and TSH responses to cold were inhibited by histidine or HA and enhanced by FA. The plasma TSH response to TRH was inhibited by histidine or HA and enhanced by FA. The inactivation of TRH immunoreactivity by hypothalamus or plasma in vitro after histidine, HA, MP or FA was not different from that of the control. These findings suggest that histamine may act both on the hypothalamus and the pituitary to inhibit TRH and TSH release, and that its effects may be mediated via H2-receptor.     

Potentiation by indomethacin of TRH-induced TSH secretion in the rat.

We have studied the effect of two inhibitors of prostaglandin synthesis on the basal and TRH-stimulated plasma TSH levels in the rat. Animals were injected sc daily with indomethacin 3 mg/0.5 ml) or aspirin (16--30 mg/0.5 ml) for 3 days. The plasma T4 and T3 were consistently lower in the indomethacin or aspirin groups than in the controls, while the basal TSH levels did not change. Indomethacin treatment significantly potentiated the TSH response to synthetic TRH (20 ng. iv) in intact and thyroidectomized rats. The pituitary TSH content was markedly increased by indomethacin, while hypothalamic TRH content did not change. In contrast, aspirin inhibited the TSH response to TRH in intact rats, when pituitary TSH content decreased significantly. No potentiation by aspirin of TRH-stimulated TSH response in the thyroidectomized rats was observed. The increased sensitivity of plasma TSH response to exogenous TRH in the indomethacin group is presumably due to higher pituitary TSH content than in the controls. The action of indomethacin appears to be mediated, at least in part, at the pituitary level. In addition, there is a dissociation between the action of indomethacin and the action of aspirin in the TSH response to TRH.     

Effects of orexin A on thyrotropin-releasing hormone and thyrotropin secretion in rats.

Effects of orexin A on secretion of thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) in rats were studied. Orexin A (50 microg/kg) was injected iv, and the rats were serially decapitated. The effects of orexin A on TRH release from the rat hypothalamus in vitro and on TSH release from the anterior pituitary in vitro were also investigated. TRH and thyroid hormone were measured by individual radioimmunoassays. TSH was determined by the enzyme-immunoassay method. The hypothalamic TRH contents increased significantly after orexin A injection, whereas its plasma concentrations tended to decrease, but not significantly. The plasma TSH levels decreased significantly in a dose-related manner with a nadir at 15 min after injection. The plasma thyroid hormone levels showed no changes. TRH release from the rat hypothalamus in vitro was inhibited significantly in a dose-related manner with the addition of orexin A. TSH release from the anterior pituitary in vitro was not affected with the addition of orexin A. The findings suggest that orexin A acts on the hypothalamus to inhibit TRH release.     

Effects of histamine and related compounds on the release of immunoreactive thyrotropin-releasing hormone from the rat stomach in vitro

Effects of histamine and related compounds on the release of immunoreactive thyrotropin-releasing hormone (ir-TRH) from the rat stomach in vitro were studied. The rat stomach was incubated in medium 199 with 1.0 mg/ml of bacitracin and 100 micrograms/ml of ascorbic acid (pH 7.4) for 20 min. The amount of TRH release into the medium was measured by radioimmunoassay. The ir-TRH release from the rat stomach was enhanced significantly in a dose-related manner with the addition of histamine and inhibited with the addition of famotidine, but not with mepyramine. The stimulatory effect of histamine on ir-TRH release from the stomach was partially blocked with the addition of famotidine, but not with mepyramine. The elution profile of acid-methanol-extracted rat stomach on Sephadex G-10 was identical to that of synthetic TRH. These findings suggest that histamine stimulated ir-TRH release from the rat stomach in vitro, and that histamine's effects may be mediated via a H2-receptor.     

Prenatal exposure of the fetal rat to excessive L-thyroxine or 3,5-dimethyl-3'-isopropyl-thyronine produces persistent changes in the thyroid control system

Studies were conducted to determine if brief exposure, in utero, to high levels of T4 or to the synthetic thyromimetic agent 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) can produce permanent disruption of the thyroid control system in a manner analogous to the changes in the "set point" reported to occur due to neonatal T4 exposure in the "neo-T4 syndrome". If such a change were to occur, it could explain the persistent thyroid disturbances seen in the progeny of hypothyroid mother rats. These latter progeny are exposed in utero to both low and high serum T4 levels. Maternal T4 treatment produced a 4-fold elevation in fetal serum T4 accompanied by a large decrease in serum TSH levels. The brief treatment in utero with high doses of T4 or of DIMIT resulted in higher neonatal mortality and the T4-treatment produce subsequent growth stunting. These treatments resulted in suppression of the fetal/neonatal thyroid which was very apparent at 5 days of age. At 30 days post-partum, the thyroid control system of the progeny of the T4 and DIMIT-treated animals was still abnormal with low serum T4 levels accompanied with normal serum TSH and T3 levels. At 60 days of age, serum T4 levels remained low in the progeny of the T4-treated animals and the TSH response to TRH was subnormal in both the progeny of the T4-treated and the DIMIT-treated animals. However, serum and pituitary TSH and serum T3 were normal. The thyroid control system of the rat is sensitive to prenatal exposure to hyperthyroxinemia as it is to postnatal exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormalities of the thyroid hormone negative feedback regulation of TSH secretion in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) are characterized by several neuroendocrine abnormalities including a chronic hypersecretion of thyrotropin (TSH) of unknown etiology. We hypothesized that the inappropriately high TSH secretion in SHR may be the result of an impaired thyroid hormone negative feedback regulation of hypothalamic thyrotropin-releasing hormone (TRH) and/or pituitary TSH production. To test this hypothesis, SHR or their normotensive Wistar-Kyoto (WKY) controls were treated with either methimazole (0.02% in drinking water) to induce hypothyroidism or administered L-thyroxine (T4) at a dose of 0.8 or 2.0 micrograms/100 g body weight/day to induce hyperthyroidism. All treatments were continued for 14 days after which animals were killed under low stress conditions. TSH concentrations in plasma and anterior pituitary tissue were 2-fold higher (P less than 0.01) in euthyroid SHR compared to WKY control rats while thyroid hormone (T3 and T4) levels were in the normal range. Hypothyroidism induced by either methimazole or thyroidectomy caused a significant (P less than 0.01) rise of plasma TSH levels in both WKY and SHR rats. However, relative to the TSH concentrations in control animals, the increase of plasma TSH in SHR was significantly blunted (P less than 0.01) in comparison to the WKY group. Hypothyroidism caused a significant depletion of TRH in stalk-median eminence (SME) tissue in both groups of rats. However, no differences between SHR and WKY rats were observed. The administration of thyroid hormone caused a dose dependent suppression of plasma TSH levels in both strains of rats. However, at both doses tested plasma TSH concentrations in SHR rats were significantly less suppressed (P less than 0.05) than those in WKY animals. Under in vitro conditions basal and potassium induced TRH release from SMEs derived from SHR was significantly (P less than 0.05) higher than that from WKY rats, whether expressed in absolute terms or as percent of content. These findings suggest that the thyroid hormone negative feedback regulation of TSH secretion may be impaired in SHR rats. Our data do not allow conclusions as to whether defects in the regulation of TSH production are located exclusively at the hypothalamic level. Since the overproduction of hypothalamic TRH and hypophysial TSH should lead to an increased thyroid hormone biosynthesis other defects in the hypothalamus-pituitary-thyroid-axis may contribute to the abnormal regulation of TSH secretion in SHR rats.     

Effect of non aromatizable androgens on LHRH and TRH responses in primary testicular failure

We have assessed the gonadotropin, TSH and PRL responses to the non aromatizable androgens, mesterolone and fluoxymestrone, in 27 patients with primary testicular failure. All patients were given a bolus of LHRH (100 micrograms) and TRH (200 micrograms) at zero time. Nine subjects received a further bolus of TRH at 30 mins. The latter were then given mesterolone 150 mg daily for 6 weeks. The remaining subjects received fluoxymesterone 5 mg daily for 4 weeks and 10 mg daily for 2 weeks. On the last day of the androgen administration, the subjects were re-challenged with LHRH and TRH according to the identical protocol. When compared to controls, the patients had normal circulating levels of testosterone, estradiol, PRL and thyroid hormones. However, basal LH, FSH and TSH levels, as well as gonadotropin responses to LHRH and TSH and PRL responses to TRH, were increased. Mesterolone administration produced no changes in steroids, thyroid hormones, gonadotropins nor PRL. There was, however, a reduction in the integrated and incremental TSH secretion after TRH. Fluoxymesterone administration was accompanied by a reduction in thyroid binding globulin (with associated decreases in T3 and increases in T3 resin uptake). The free T4 index was unaltered, which implies that thyroid function was unchanged. In addition, during fluoxymesterone administration, there was a reduction in testosterone, gonadotropins and LH response to LHRH. Basal TSH did not vary, but there was a reduction in the peak and integrated TSH response to TRH. PRL levels were unaltered during fluoxymesterone treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

The thyroid reserve in children with chronic lymphocytic thyroiditis revealed by the thyrotropin-releasing hormone and thyroid-stimulating hormone tests

Serum thyroid hormone and TSH concentrations were measured before and after the administration of TRH (10 micrograms/kg body weight) and bovine TSH (10 IU) in 14 children with chronic lymphocytic thyroiditis. The TRH test showed that the responsiveness of TSH was positively correlated with the basal TSH (P less than 0.001) and inversely with the increase in serum thyroid hormones, for delta T3 (P less than 0.05) and for delta T4 (P less than 0.001). Overall, the patients had significantly lower mean values for basal T4, but not for T3. The TSH test revealed that the delta T3 was positively correlated with delta T4 (P less than 0.05). delta T3 after TSH administration was positively correlated with it after TRH (P less than 0.05). The patients were divided into three groups on the basis of their peak TSH values after TRH administration. In Group 1 (peak value below 40 microU/ml; N = 5); T3 increased significantly after TRH and TSH administrations (P less than 0.05 and P less than 0.025, respectively). In addition, delta T4 was significant after TSH administration. In Group 2 (peak TSH above 40 and less than 100 microU/ml; N = 6); only delta T3 after TRH was significant (P less than 0.05). In Group 3 (peak TSH above 100 microU/ml; N = 3); the response of thyroid hormones was blunted. Thus, the thyroid hormone responses to endogenous TSH coincided with that to exogenous TSH, and the exaggerated TSH response to TRH indicates decreased thyroid reserve.     

Thyroid hormone regulation of messenger ribonucleic acid encoding thyrotropin (TSH)-releasing hormone is independent of the pituitary gland and TSH

Cellular levels of mRNA encoding pro TRH in the rostral paraventricular nucleus are reduced by thyroid hormones. To determine whether this regulatory effect of thyroid hormones requires a functional pituitary gland or, specifically, TSH, we examined the effect of T3 on proTRH mRNA in hypophysectomized, thyro-parathyroidectomized male rats with or without bovine TSH replacement. Hypophysectomy plus thyro-parathyroidectomy reduced serum T4 and TSH to undetectable levels in all animals and elevated TRH mRNA in the paraventricular nucleus over that of sham-operated animals. Eleven consecutive daily injections of T3 significantly reduced TRH mRNA levels in both sham controls and thyro-parathyroidectomized rats. However, 11 daily injections of bovine TSH (1 U/day) failed to alter the effect of T3 on TRH mRNA levels. These results demonstrate that the regulatory influence of thyroid hormones on the biosynthesis of TRH within the thyrotropic center of the brain is independent of the pituitary gland and of TSH.     

Dopamine inhibits thyrotropin-releasing hormone release from rat adrenal gland in vitro

The effects of dopamine on the release of thyrotropin-releasing hormone (TRH) from the rat adrenal gland were studied in vitro. The rat adrenal glands were incubated in medium 199 with 1.0 mg/ml of bacitracin and 100 micrograms/ml of ascorbic acid (pH 7.4) (medium) for 20 min. The amount of TRH release into the medium was measured by radioimmunoassay. The immunoreactive TRH (ir-TRH) release from the rat adrenal gland was inhibited significantly in a dose-related manner with the addition of dopamine and enhanced with the addition of pimozide or domperidone to the medium. Dopamine's effects on ir-TRH release from the adrenal gland were blocked with the addition of pimozide or domperidone. The elution profile of methanol-extracted rat adrenal gland was identical to that of synthetic TRH. The findings suggest that the dopaminergic system inhibits TRH release from the rat adrenal gland.     

Long-term perspectives of thyroxine administration in neonatal rats.

Newborn pups were injected with normal saline (group A) and exogenous thyroxine (group B). Elevated T4 and decreased TSH levels from day 7 in group B continued until day 35. T4 and TSH were in normal range by day 42 and were similar to group A. Weight gain was significantly lower in group B. On day 45, half hourly injections (subcutaneous) of TRH were given to half of group A and group B each. Remaining halves were injected with saline. TSH response to TRH was significantly decreased in group B rats. Thus, neonatal hyperthyroidism results in (1) permanent decrease in pituitary reserve of TSH secretion and (2) a permanent imprinting regarding growth and thyroidal development and thus, neonatal period is critical for thyroidal development.     

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.     

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.     

Maternal leptin treatment during lactation programs the thyroid function of adult rats

Recently, we showed that both maternal malnutrition during lactation and leptin treatment during the neonatal period program thyroid function. In this study we evaluate whether maternal leptin treatment during lactation programs thyroid function of the offspring in the adulthood. The dams were divided into 2 groups: Lep-daily sc single injected with 8 microg/100 g of body weight with recombinant rat leptin during the last 3 days of lactation and control group (C) that received the same volume of saline. The 180 day-old animals received a single i.p. injection of (125)I (2.22x10(4) Bq) and they were killed 2 h after the injection. Triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH) and leptin concentrations were measured by radioimmunoassay. The milk of leptin-treated mothers on the last day of treatment had higher leptin (p<0.05) concentration. The pups of the leptin-treated mothers had at 21 days an unchanged T3, T4 and leptin serum concentrations with higher TSH (p<0.05). The offspring of Lep mothers had at 180 days a higher T3 (p<0.05) with normal thyroid (125)I uptake, T4 and TSH serum concentrations compared to the controls. So, the mother's hyperleptinaemia during lactation programs to a higher T3 serum concentration on the offspring, probably by a higher leptin transfer through the milk.     

Prolactin as a marker of dopaminergic activity at different levels of thyroid function in man

To investigate the hypothesis of an altered dopaminergic activity in hypothyroidism, seven patients without thyroid tissue were studied by means of three consecutive tests: an iv bolus of TRH (200 micrograms); a continuous iv infusion (5 mg during 30 min) of metoclopramide (MCP); and a second, post-MCP, iv bolus of TRH (200 micrograms). The study was performed three times: (A) without treatment; (B) on the 15th day while on L-T4 (150 micrograms i.d.); and (C) on the 30th day with the same treatment. Each time was a different situation of thyroid function; on the basis of basal serum TSH (P less than 0.001, A vs B vs C). The response of PRL to the first (non-primed) TRH, expressed as the sum of increments in ng/ml (mean +/- SE), was significantly higher in A (659 +/- 155) than in C (185 +/- 61). Individual PRL responses correlated with circulating T3 (P less than 0.02), but not with T4. A significant increase of PRL occurred after MCP in the three situations, but there were no differences among them. Likewise, the responses to the second (MCP-primed) TRH showed no differences. Although there was an expected high correlation (P less than 0.001) between basal TSH and circulating thyroid hormones, the maximal response of TSH to both non-primed and MCP-primed TRH was in B. After MCP, no measurable increase of TSH could be demonstrated at any of the three levels of thyroid function. These results do not support the hypothesis of an altered dopaminergic activity in hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)     

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 opioid peptides on thyrotropin-releasing hormone release from the rat caecum in vitro

Effects of opioid peptides (beta-endorphin, dynorphin (1-13). alpha-neoendorphin, beta-neoendorphin, leucine-enkephalin, methionine-enkephalin) on the release of thyrotropin-releasing hormone (TRH) from the rat caecum were studied in vitro. The rat caecum was incubated in medium 199 with 1.0 mg/ml of bacitracin (pH 7.4) (medium). The amount of TRH release from the rat caecum into the medium was measured by radioimmunoassay. The immunoreactive TRH (ir-TRH) release from the rat caecum was inhibited significantly in a dose-related manner with the addition of opioid peptides. The inhibitory effects of opioid peptides on ir-TRH release from the rat caecum were blocked with an addition of naloxone. The elution profile of acid-methanol-extracts of rat caecum on Sephadex G-10 was identical to that of synthetic TRH. The findings suggest that opioid peptides inhibit TRH release from the rat caecum in vitro.     

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)