Monodeiodinating Activity Research Articles

Divergent deiodination of thyroid hormones in the separated parts of the fetal and maternal placenta in pigs.

Previous work from this laboratory has shown that the thyroid gland of the fetal pig begins to function at about day 46-47 (0.40-0.415 fraction of gestational age). Sera from fetuses contain lower thyroxine (T4), 3,3',5-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) concentrations than maternal sera, except for about 2 weeks before term. The fetal T4 metabolism is dominated by the 5'-monodeiodinating activity (5'-MD). In the present study we measured the iodothyronines content, and the outer (5'-MD) and inner (5-MD) monodeiodinases activity, in homogenates of the placenta. The pig placenta, which is of the epitheliochorial type, was separated into the fetal and the maternal part. The concentrations of T4, T3 and rT3 were lower, and the deiodinating activity of 5'-MD and 5-MD higher, in the fetal than in the maternal placenta. The fetal placenta not only deiodinated more actively T4 to T3 and T4 to rT3, but degraded T3 to 3,3'-diiodothyronine (3,3'-T2) more actively than rT3 to 3,3'-T2. Such divergent deiodinating activity of T4 to T3, T3 to 3,3'-T2 and rT3 to 3,3'-T2 might favor establishing a relatively high and constant rT3 concentrations in fetal and maternal placentas, and a lower T3 in the fetal placenta. The inner ring deiodinating activity (excluding a day before parturition) was always more active in the fetal placenta, while the outer ring deiodinations varied in this respect, depending on the gestation stage. These results support the hypothesis that in the fetal pig, enzymatic deiodination of thyroid hormones forms a barrier which reduces transplacental passage of the hormones and that the fetal part of the placenta is the primary factor in the mechanism regulating the hormonal transfer. In spite of the presence of the barrier, there is an adequate maternal supply of thyroid hormones to the fetus in early gestation, which suggests that the enzymatic mechanism is influenced in some way by the thyroid status of the fetus.

The development of a radioimmunoassay for reverse triiodothyronine sulfate in human serum and amniotic fluid.

Sulfated iodothyronines including T4-sulfate (T4S) and T3-sulfate (T3S) have been identified in human serum and amniotic fluid. Little is known, however, about the existence of sulfate conjugation of reverse T3 (rT3S) in man. In this report, we employed a novel, sensitive, and specific rT3S RIA to address this question. The rabbit antiserum to rT3S was highly specific; T4, T3, rT3, and 3,3'-T2 showed less than 0.002% cross-reaction with the antiserum. Only T4S and T3S cross-reacted significantly (0.3% and 0.01%, respectively); other analogs cross-reacted less than 0.0001%. The detection threshold of the RIA was 14 pmol/L (1.0 ng/dL). The mean serum rT3S concentration (pmol/L) was 40 in euthyroid subjects. Values were similar in hypothyroid patients (38) and pregnant women (52) but significantly (P < 0.01) elevated to 176 in hyperthyroid patient, 74 in patients with nonthyroid illnesses, and 684 in cord sera of newborns. Serum rT3S increased significantly in hyperthyroid patients 1 day after administration of 1 g sodium ipodate orally. Reverse T3S was detected consistently in amniotic fluid at 14 to 22 weeks of gestation and showed a marked rise 1-3 weeks after intraamniotic administration of 500-1000 micrograms T4. The various data suggest that: (1) rT3S is a normal component of human serum and amniotic fluid; (2) it is derived from metabolism of T4 or rT3; (3) circulating rT3S increases in hyperthyroidism and in circumstances where type I 5'-monodeiodinating activity is low, e.g. nonthyroid illnesses, fetal life, and after administration of ipodate.

Endogenous growth hormone controls high plasma levels of 3,3′,5-triiodothyronine (T 3) in growing chickens by decreasing the T 3-degrading type III deiodinase activity

The influence of endogenous GH levels on peripheral monodeiodination activity has been investigated in growing chickens at the age of 4 weeks, when they normally show no T 3 increase after GH injection. Injection of anti-GH serum decreased plasma T 3 and increased plasma T 4. Three d and 1 week after hypophysectomy, plasma T 3 was also markedly decreased, while T 4 was only slightly affected, hepatic 5′D-I activity showed a transient decrease, but 5D-III activity was highly increased, as were the number of hepatic GH receptor sites. Injection of GH in hypophysectomized chickens decreased 5D-III activity and increased plasma T 3. GH receptor-deficient dwarf chickens had decreased plasma T 3 and increased plasma T 4 and hepatic 5′D-I and 5D-III activities compared to their normally-growing siblings. GH administration could only affect T 3 and 5D-III in the non-dwarf siblings, which showed higher basal 5D-III activity compared to the non-responsive age-matched chickens of the Hisex strain used in the other experiments. It can be concluded that endogenous GH is an important factor in the control of plasma T 3 levels in growing chickens due to its influence on the activity of the T 3-degrading type III deiodinase. The effectiveness of exogenous GH administration to acutely increase plasma T 3 probably depends on the balance between the injected dose and the endogenous GH concentration, the hepatic GH receptor availability and the hepatic type III deiodinase level.

Evidence for the kidney as an important source of 5′-monodeiodination activity and stimulation by somatostatin in Oreochromis niloticus L

Radioimmunoassay of 3,5,3′-triiodothyronine (T 3) and thyroxine (T 4) in the thyroidal region of mature male Oreochromis niloticus revealed stores of T4 but negligible levels of T 3, yielding a very low T 3/T 4 ratio (0.3%). 5′-Deiodination (5-D) of T 4 into T 3 was examined in liver and kidney homogenates in vitro by radioimmunoassay of T 3 with T 4 as substrate. In both organs, the 5′-D activity was temperature dependent: at 4°C, T 3 production was below the level of detection and maximal in both tissues at 37°C; and at 45°C, the enzymatic activity was reduced. T 3 production seemed to reach a plateau after 60 min of incubation. The reaction required exogenous thiol cofactor (dithiothreitol) and was inhibited partially or completely by propylthiouracil depending on the concentrations used. Hepatic and renal 5′-D activities were stimulated by somatostatin (SRIF) within 4 hr, but a subsequent increase in plasma T 3 was observed only when SRIF was injected together with T 4, while the magnitude of rT 3 production decreased. It is concluded that almost all the circulating T 3 is provided by peripheral T 4 to T 3 conversion since T 3 RIA in thyroidal follicles demonstrated insignificant T 3 production. The kidney may contain the large part of the functional deiodinase which converts T 4 into T 3. As in mammals and unlike in other fishes, there is not only 5′-D activity, but also 5-D activity, and both may be influenced by SRIF.

Analysis of nuclear 3,3',5-triiodothyronine receptor in the brown adipose tissue (BAT) of the postnatal lamb.

Postnatal thermogenesis in sheep is associated with increased sympathoadrenal activities, a T3 surge and an enhanced brown adipose tissue (BAT) type II 5'-monodeiodinating (5'-MDI) activity. The latter peaks 3-4 days after birth and is known to be important in generating intracellular T3 for nuclear receptor binding. In order to further investigate the mechanism(s) responsible for neonatal thermogenesis, thyroid hormone nuclear receptor (T3NR) binding characteristics were quantified in lamb BAT from newborn (NB) to 30d of postnatal age. Maximal binding capacities (MBC, mean +/- SEM fmoles T3/mg DNA) in BAT showed a decrease as studied by ANOVA during the first 11 days (NB to 1d, 148 +/- 24 [N = 5, p < 0.01, cf. 3-5d group]; 3-5 d, 61 +/- 5.5 [N = 5]; 10-11d, 72 +/- 9.1 [N = 4]). Afterwards, MBC increased at 30d (196 +/- 32, N = 4, p less than 0.01, cf. 3-5d group). BAT T3NR binding affinities (10(9) M-1) were comparable in all age groups studied (NB-1d, 2.8 +/- 0.3; 3-5d, 3.4 +/- 0.3; 10-11d, 4.0 +/- 1.1; 30d, 2.4 +/- 0.4). The data suggest that the postnatal surge in T3 and type II 5'-MDI is accompanied with a concurrent decrease in MBC of BAT T3NR. The latter may represent a down-regulation of T3NR presumably in an attempt to regulate the overall effect of thyroid hormone in neonatal thermogenesis.

Identification of thyroxine-sulfate (T4S) in human serum and amniotic fluid by a novel T4S radioimmunoassay.

Recently, we identified significant amounts of thyroxine sulfate (T4S) in fetal sheep serum, meconium, bile, and amniotic and allantoic fluids. Little is known, however, about sulfate conjugation of thyroxine in humans. In this study, we employed a novel, sensitive T4S RIA to address this question. The rabbit antiserum was quite specific; T4, T3, rT3, and 3,3'-T2 showed less than 0.002% cross-reactivity. Other analogs cross-reacted less than 0.0001%. Only rT3S and T3S cross-reacted significantly (9.9% and 2.0%, respectively). The mean serum T4S concentration (ng/dL) was 8.6 in euthyroid subjects, 14.4 in hyperthyroid subjects, 5.0 in hypothyroid subjects, 5.9 in pregnancy, and 4.5 in patients with nonthyroid illnesses. T4S concentration in amniotic fluid from women at 18-19 weeks of gestation (25.5 ng/dL) was higher than that at 14-15 weeks of gestation (14.3 ng/dL). A significant rise in serum T4S was detected in hyperthyroid patients 1 day after ingestion of 1 g of ipodate. These data suggest that T4S is a normal component of human serum and amniotic fluid, and it is mostly derived from T4 peripherally and accumulates when type I 5'-monodeiodinating activity is low in fetuses or inhibited by drugs, such as ipodate.

Food Intake After Hatching Inhibits the Growth Hormone Induced Stimulation of the Thyroxine to Triiodothyronine Conversion in the Chicken

The effect of a single injection of 10 micrograms chicken GH on circulating thyroid hormones as well as in vitro liver 5'-monodeiodination (5'-D) activity was studied in posthatch chicks submitted to different feeding conditions. One group was normally fed after hatching, a second group was only fed after three days and a third group was food deprived after 2 days of feeding. Combination of all results indicates that the start of food intake abolishes the stimulatory effect of a GH injection on circulating T3 and liver 5'-D activity. Food deprivation after a period of food intake restores the GH effect on plasma T3 but not on liver 5'-D.

Effect of Lactational Intensity on Extrathyroidal 5’-Deiodinase Activity in Rats

Concentrations of thyroxine and triiodothyronine in serum and 5’-monodeiodination activity in liver and kidney were studied in lactating Sprague-Dawley rats with different litter sizes. Litter sizes were adjusted at birth to 0 (postpartum nonlactating group), 4, 8, 12, and 16 pups per lactating rat. Serum and tissue samples were collected from lactating rats and pups on d 12 of lactation and from 6 nulliparous females. Nulliparous and postpartum nonlactating rats did not differ in serum thyroxine, triiodothyronine concentrations, or in 5’-deiodinase activity in liver and kidney. As litter size increased, maternal serum thyroxine, triiodothyronine concentrations, and 5’-deiodinase activity in liver and kidney decreased. Growth rate of pups was inversely correlated with litter size and positively correlated with concentration of serum thyroxine and liver 5’-deiodinase in mothers. In pups, serum triiodothyronine concentrations decreased as litter size increased, but serum thyroxine concentrations were not affected. Results suggest a relationship between the hypothyroid status of lactating rats and suckling intensity. The thyroid status of the dam may influence thyroid status and the dam may influence thyroid status and growth of offspring.

Growth Hormone Induced Stimulation of the T4to T3Conversion in Fed and Fasting Dwarf Goats

Fed and food deprived (7 days) adult dwarf goats were injected intravenously with 75 micrograms/kg b. w. of ovine growth hormone (o-GH). Blood samples were collected from the jugular vein -2, -1 and 0 hr prior to and 30, 60, 90 and 120 min after injection and assayed for thyroxine (T4) and triiodothyronine (T3) concentrations. The 5'-monodeiodination (5'-D) activity was consequently determined in liver and kidney samples following slaughtering. Fasting alone increased plasma concentrations of T3 and T4, whereas injection of o-GH raised T3 additionally and more profoundly in food deprived animals compared to fed ones. A small increase in plasma T4 was also observed following o-GH injection, but only in starved goats. At the same time the hepatic, but not the kidney, 5'-D activity was stimulated in food deprived and GH injected animals. It is concluded that during prolonged fasting an increased peripheral T4 to T3 conversion is occurring contrary to the known decrease in T3 production during short periods of food deprivation. This increased conversion may be under the control of GH.

Failure to relate thyroid hormones and in vitro 5′-monodeiodination activity to oocyte development and sex steroids in the giant swamp frog Dicroglossus occipitalis at the equator

Females of the giant swamp frog Dicroglossus occipitalis were captured in Zaïre close to the equator in the course of 1 month. During this period, females with fully developed eggs were found, together with females of which the eggs were still in the first developmental stages. A close relationship was established between the maturation of the eggs and the studied gonadal factors: the gonadosomatic index, the oviduct weight, plasma estradiol-17β (E 2) concentrations, plasma testosterone concentrations, and the total ovarian E 2 concentrations. At the level of the thyroidal axis, the studied factors (plasma thyroxine (T 4), plasma triiodothyronine (T 3), plasma T 3 T 4 ratio, T 4 and T 3 concentrations, and the T 3 T 4 ratio in the thyroids and the 5′-monodeiodination activity (5′-D-activity) in the skin and kidney homogenates) did not show parallel changes with the maturation process of the eggs. These results indicate that no causal relation has to exist between the annual variation in thyroid hormones and the annual reproductive patterns as found in frogs from the tropical or temperate climatic region.

Two Pathways for Thyroxine 5’-Monodeiodination in Brown Adipose Tissue in Fetal Sheep: Ontogenesis and Divergent Responses to Hypothyroidism and 3,5,3’- Triiodothyronine Replacement*

Thermogenesis in rat brown adipose tissue (BAT) is thyroid hormone responsive. Rat BAT expresses a type II 5'-iodothyronine monodeiodinase (5'MDI) which mediates local T3 production from T4. Earlier studies show that BAT from fetal and newborn sheep contains a high Km type I, instead of type II, 5'MDI. To better characterize the 5'MDI of ovine fetal BAT, we studied the in vitro monodeiodination of [125I]T4 at a low substrate concentration (2 nM) and in the presence of 1 mM propylthiouracil in BAT homogenates of control and thyroidectomized fetuses at different gestational ages as well as in newborn lambs. Thyroidectomies were performed at three gestational ages: 99-107 days (group 1), 129-132 days (group 2), and 115-117 days (group 3A). Animals were studied 8-13 days after surgery. A significant increase in the activity of a low Km T4 5'MDI was noted in BAT from hypothyroid fetuses at all three gestational ages. This low Km activity was similar to the type II enzyme in rat BAT and brain in that the activity was also T3 resistant. A gradual rise in BAT type II 5'MDI activity was measured between 99 days gestation and term (150 days). These results indicate that ovine BAT contains two distinct iodothyronine 5'-monodeiodinating activities, one with a high Km and another with a low Km. The latter, resembling the type II 5'MDI in rat brain and BAT, is increased in ovine hypothyroid BAT. The former predominates in euthyroid tissue and is similar to the type I 5'MDI characterized in rat liver, kidney, and thyroid. We speculate that BAT type II 5'MDI may be important for neonatal BAT thermogenesis, while the type I enzyme may play a significant role in the increase in serum T3 concentration that occurs at birth.

The effect of fasting on thyroidal T4-5'monodeiodinating activity in mice

Complete fasting induces a significant decrease of serum T3 and a fall in TSH in rodents and man. To evaluate the effect of starvation on thyroidal T4 5'monodeiodinating activity, in vitro conversion of T4 to T3 by thyroid and liver homogenate from one to three days fasted mice was compared with homogenates from control mice on animal chow. 5'monodeiodinating activity was significantly lower in thyroid homogenates of fasted mice than in those of chow-fed control [100 +/- 5.0 and 92 +/- 5.0 pmol T3.(mg protein)-1.h-1 at 48 and 72 h fasting, respectively, vs 132 +/- 5.0 pmol T3.(mg protein)-1.h-1 of fed control, p less than 0.01]. A similar decrease in thyroidal 5'monodeiodinating activity was seen in the liver. The decrease in thyroidal 5'monodeiodinating activity induced by fasting was not reversed by the supplementation of homogenates with the thiol-protecting agent, dithiothreitol (0.2-4.0 mmol/l). Physiological replacement of T4, 0.58 nmol.(100 g)-1.day-1, did not alter the effect of starvation in either the thyroid or liver. TSH (0.02 IU/day) injection, on the other hand, stimulated 5'monodeiodinating activity in homogenates of thyroids from 3-days fasted mice which was no different from TSH-treated fed control. It is postulated that starvation-induced decrease in thyroidal T4 to T3 converting activity may play a role, together with decreased hepatic 5'monodeiodinating activity, in fasting-induced low serum T3 in mice.

Ontogeny of the effect of purified chicken growth hormone on the liver 5′ monodeiodination activity in the chicken: Reversal of the activity after hatching

The ontogeny of the effect of chicken growth hormone (c-GH) on the liver 5′ monodeiodination (5′-D) activity was studied in chickens starting from 14-day-old embryos until 5-week-old chickens. Ten micrograms of the purified hormone was ibjected intravenously and after 2 hr, blood and liver samples were taken. In all embryonic stages tested, c-GH stimulated the peripheral thyroxine (T 4) to triiodothyronine (T 3) conversion as demonstrated by the increased plasma T 3 level and liver 5′-D activity while the plasma reverse T 3 (rT 3) level was decreased. In chicks 1 day after hatching, GH was still able to increase the plasma T 3 level and the liver 5′-D activity. However, in 2-day-old chicks, this stimulation had completely disappeared, while the control value of the plasma T 3 T 4 ratio was considerably higher than the day before. The effect of c-GH injection gradually turned into a decrease of 5′-D activity and plasma T 3 in 5- and 7-day-old chicks. Further on, no effect of c-GH could be found in 2- to 4-week-old growing chickens, but in 5-week-old GH-injected animals the plasma T 4 and rT 3 level decreased again, although no significant effect on T 3 or liver 5′-D activity could be demonstrated.

Induction of Type II T4-5’-Monodeiodiriase Activity in Brown Adipose Tissue in Fasted Mice

In order to study the effect of starvation on brown adipose tissue (BAT) type II 5'-monodeiodinating activity (5'MDI), type II 5'MDI was measured in vitro in the presence of 20 mM dithiothreitol, 1 mM propylthiouracil, 2 nM thyroxine (T4) and appropriate amounts of 600 X g infranatant of BAT from fed control or 3 day fasted mice, with or without daily T4 replacement (1.2 micrograms/100 g bw) during starvation. I- released from 125I-T4 was measured by ion-exchange column chromatography. Activity of BAT 5'MDI was markedly elevated in the 3 day fasted group (133 +/- 28 fmol I-/h per mg protein vs. 26 +/- 6.4; p less than 0.05). Kinetic studies using BAT infranatant suggested that fasting-induced activity is associated with a similar change in the Vmax, but no demonstrable change in apparent Km of T4 monodeiodination. T4 replacement during fasting, which normalized both serum T4 and T3 in fed and 3 day fasted groups, did not stop the increase of BAT 5'MDI in the fasted group (p less than 0.01). The data suggest that: (1) the fasting-induced increase in BAT 5'MDI is due mainly to the changes in capacity rather than the affinity of the enzyme, and (2) the fasting-induced increase in BAT 5'MDI is not mediated entirely through changes in serum thyroid hormone concentration.

Impaired peripheral T3 production but normal induced thyroid hormone secretion in the sex-linked dwarf chick embryo

Plasma concentrations of thyroxine (T4), triiodothyronine (T3) and chicken GH (cGH), together with hepatic 5'-monodeiodination (5'-D) activity, were measured in normal (Dw) and dwarf chick (dw) embryos at incubation d 18. An injection of 10 micrograms of ovine GH (oGH) raised plasma concentrations of T3 in Dw embryos after 1 and 2 h and stimulated hepatic 5'-D activity after 2 h. A non-specific increase in T4 was also observed after 1 h in Dw animals probably due to the heterologous nature of the injection. These effects were not observed in dw embryos. An injection of 1 microgram of TRH was able to increase cGH levels after 15 min in Dw embryos, whereas the the observed increase in the dw group was not significant. In Dw embryos, 0.01, 0.1 and 1 microgram of TRH increased plasma concentrations of T3 in a dose-dependent way, whereas in dw embryos, no reaction to the TRH injections was seen, except for the highest dose used. Contrary to this observation, T4 was increased to the same level in both Dw and dw embryos following TRH injections. An injection of 1 microgram of ovine CRH increased corticosterone after 0.5 h and elevated T3 and T4 after 2 h to the same extent in Dw and dw embryos. It is concluded that the thyrotrophic activities of TRH and oCRH and the corticotropic activity of oCRH do not differ between normal and sex-linked dwarf embryos. However TRH and GH were unable to stimulate the T4-T3 conversion in the liver of dw embryos, presumably due to the lack of hepatic GH receptors in these animals.

Thyrotropic activity of the ovine corticotropin-releasing factor in the chick embryo

An injection of several doses of ovine corticotropin-releasing factor (oCRF) was made into an allantoic blood vessel of 18-day-old chick embryos. All doses used (0.5, 1, 2, and 5 μg) induce a quick increase of plasma corticosterone concentrations after 15 and 30 min and 1 and 2 hr and this in a dose-dependent manner with the high doses having a prolonged effect lasting up to 2 hr. An increase in plasma levels of thyroxine (T 4) and triiodothyronine (T 3) was observed after 1 and 2 hr. After the oCRF injection, no stimulation of the hepatic 5′-monodeiodination activity was observed and there was no increase, but even a small decrease in the T 3 to T 4 ratio could be calculated. It was therefore concluded that oCRF in the chick embryo has a thyrotropic effect presumably by stimulating the release of thyrotropin from the pituitary.

Estradiol-17β silastic implants in female Rana ridibunda depress thyroid hormone concentrations in plasma and the in vitro 5′-monodeiodination activity of kidney homogenates

Estradiol-17β-containing silastic tubings were implanted in female Rana ridibunda. Preliminary data, concerning in vitro incubations of such tubings in saline media, revealed that high concentrations of estradiol were released out of the tubings in the incubation medium. Compared to control-implanted frogs, the frogs that had the estradiol tubings implanted for 30 days showed a significant increase of the plasma estradiol concentration, the ovarian estradiol concentration, and the weight of the oviduct. Plasma triiodothyronine (T 3) levels, plasma thyroxine levels, and the in vitro T 3 production in the kidney homogenates were significantly decreased. These results indicate that high estradiol levels not only influence the gonadal axis, but also cause important effects on the thyroidal axis.

A simultaneous stimulation of the peroxidase activity in the thyroid gland and the hepatic monodeiodination, associated with a decrease in hepatic thiol groups, during chronic cold exposure of rats

Male Wistar rats were subjected to a 16-day long cold exposure of 4°C. These rats are characterized by a higher food intake, but a slower growth rate. The plasma thyroxine (T 4) concentration is decreased and the triiodothyronine (T 3) concentration is increased while the reverse triiodothyronine (rT 3) level remains unchanged during the cold period. At the end of the cold exposure an increased 5′ monodeiodinating activity in the liver is observed whereas at the same time the liver total, as well as the non-protein −SH concentration, is significantly decreased. In the kidney the 5′monodeiodination and the SH concentration remain unchanged after the cold exposure. In the cold exposed rats the increased peroxidase activity in the thyroid gland is associated with significant decreased levels of T 4 and unchanged levels of T 3 in the thyroid homogenate. These results suggest that the altered thyroid hormone levels after cold exposure are caused by a simultaneous stimulation of the thyroid gland function and the 5′ monodeiodination in the liver.

Evidence for chicken GH as the only hypophyseal factor responsible for the stimulation of hepatic 5'-monodeiodination activity in the chick embryo.

The influence of an intravenous injection of chicken growth hormone (cGH), a total chicken pars distalis (PD) extract, and a PD extract depleted of cGH by immunoadsorption was studied in the 18-d-old chick embryo. Plasma concentrations of triiodothyronine (T3), thyroxine (T4), and hepatic 5'-monodeiodination (5'-D) activity were measured. An injection of total PD extract raised plasma T3, T4, and 5'-D activity, whereas a PD extract depleted of GH only increased plasma T4. The amount of cGH present in the PD extracts, as measured by homologous cGH radioimmunoassay, increased T3 and raised liver 5'-D, but had no effect on plasma T4. The effect on liver 5'-D was more pronounced with cGH than with a total PD extract, whereas the effect on plasma T3 was somewhat less pronounced. It was concluded that cGH increased the peripheral conversion of T4 into T3 in the chick embryo, whereas a PD extract depleted of cGH was purely thyrotropic. The PD extract also seemed to have 5'-D-suppressing activity.

Effect of the sex-linked dwarf gene on thyrotrophic and somatotrophic axes in the chick embryo.

Plasma concentrations of thyroxine (T4), triiodothyronine (T3), reversed triiodothyronine (rT3), and insulin-like growth factors I and II (IGF-I, IGF-II) together with peripheral 5'-monodeiodination activity were measured in both normal and sex-linked dwarf embryos between day 14 of incubation and day 1 posthatch. Plasma T4 levels increased gradually during embryonic development while T3 concentrations remained low until day 20, when a sharp increase was observed. rT3 levels also increased from day 14 and dropped on day 20 when T3 levels started to increase. 5'-monodeiodination activity was high on day 14 of incubation, decreased thereafter, and showed an increase at the time of air sac penetration together with increased T3 levels. At this stage, differences between normal and dwarf embryos were observed; the latter had lower nonsignificant 5'-Monodeiodination activity and lower (P less than 0.01) plasma T3 levels. Plasma IGF-II levels were high during the whole embryonic period studied. Dwarf embryos had lower (P less than 0.05) IGF-II levels at the time of hatching. IGF-I levels were high on days 14 and 16, declined afterwards, and started to increase again around hatching. With the exception of T3 and IGF-II levels, introduction of the dwarf gene did not cause major changes in the hormonal parameters studied. This may explain the identical body weight at hatching.