The thyroid and photoperiodic control of seasonal reproduction in American tree sparrows (Spizella arborea)

To explore the role of the thyroid gland in the control of seasonal reproduction in obligately photoperiodic American tree sparrows (Spizella arborea), the effects of (1) thyroxine administered in drinking water to thyroid-intact photosensitive or photorefractory birds, and (2) radiothyroidectomy before and after photostimulation and during photorefractoriness were examined. Chronic administration of pharmacological doses of thyroxine induced testicular growth and usually regression in initially photosensitive birds held on short or intermediate daylengths. Some thyroxine-treated birds with regressed testes were absolutely photorefractory, but most remained photosensitive. Exogenous thyroxine never induced testicular growth in photorefractory birds moved to short days, though it often impeded, and sometimes even blocked, the recovery of photosensitivity. Although circumstantial, these effects of exogenous thyroxine are consistent with an hypothesis that assigns to thyroid hormones two roles — one stimulatory and the other inhibitory — in the control of seasonal reproduction. Radiothyroidectomy before photostimulation inhibited (but did not prevent) photoinduced testicular growth, blocked spontaneous testicular regression, suppressed molt, and prevented photorefractoriness. Moreover, as demonstrated by testicular growth after thyroxine replacemnt therapy, radiothyroidectomy during photorefractoriness later restored photosensitivity despite continued photostimulation. Thus, euthyroidism is an essential condition for maximizing (but not for initiating) photoinduced testicular growth and for triggering and maintaining photorefractoriness in photostimulated tree sparrows. However, when performed early during photostimulation, radiothyroidectomy neither immediately induced nor later blocked spontaneous testicular regression. Thus, endogenous thyroid hormones and long days may interact during a critical period to program a sequence of physiological events that plays out as photorefractoriness in chronically photostimulated birds. Such an organizational event cannot be permanent, for seasonal reproduction is episodic and its control mechanism necessarily cyclic. Because thyroidectomy simulated the well-known restorative effect of short days (and exogenous thyroxine impeded it), short days may dissipate photorefractoriness by creating a milieu wherein thyroid hormones are deficient or inactive.Abbreviations ANOVA analysis of variance - bTSH bovine thyroid stimulating hormone - GnRH gonadotropin-releasing hormone - LH luteinizing hormone - nL: nD daily light: dark regime (n is duration in hours) - SEM standard error of the mean - SNK Student-Newman-Keuls test - T₄ thyroxine - TH thyroid hormone - TR thyroid hormone receptor     

Hierarchies in the energy budget: Thyroid hormones and the evolution of human life history patterns

The evolution of human life history characteristics required dramatic shifts in energy allocation mechanisms compared with our primate ancestors. Thyroid hormones, such as thyroxine (T4) and triiodothyronine (T3), are sensitive to energy balance, and are significant determinants for both tissue-specific and whole-body metabolic rate. Thus, thyroid hormones are in part responsible for setting the body's overall energy budget and likely played an important role in the evolution of human life history patterns. We propose that the dynamics of mammalian T3 production, uptake, and action have evolved so that energy allocation prioritizes the high demands of brain development and functioning, often at the expense of growth and reproduction. This paper explores the role of thyroid hormone dynamics in the evolution of human encephalization, prolonged childhood and adolescence, long lifespans, reproduction, and human aging.     

甲状腺激素对豚鼠卡那霉素中毒性耳聋的预防作用

卡那霉素、庆大霉素等抗生素常引起耳聋,目前尚无较好的防治方法。卡那霉素对内耳的毒性作用,主要先影响有关的酶功能,继而破坏毛细胞而致聋。甲状腺激素具有促进蛋白质合成、增强细胞生物氧化的功能。因此可能具有减轻卡那霉素耳毒性的作用。本实验以耳廓反射、内耳生物电及耳蜗铺片为指标,观察甲状腺激素对卡那霉素耳中毒的预防。实验豚鼠分两组,各13只,对照组每天注射卡那霉素300mg/kg,共10天;甲状腺素组先隔天服甲状腺片20mg共四次,以后给予与对照组相同剂量卡那霉素,同时仍隔天服甲状腺片20mg直至停药后16天,前后总共服17次。结果:(1)耳廓反射阈变化,对8、4、2KHz三个频率听力均下降的耳,对照组为11只耳,甲状腺素组为3只耳,两者差异显著。听力下降的频率范围及程度,对照组比甲状腺素组更大。对照组听力下降开始出现的时间明显早于甲状腺素组;(2)内耳生物电,0～80dβ不同程度短声引起的耳蜗微音器电位与听神经动作电位幅值甲状腺素组动物均高于对照组;(8)耳蜗铺片,对照组大部分动物耳蜗各回的毛细胞严重变性缺损,甲状腺素组耳蜗病变仅局限在底回。以上结果表明甲状腺激素能减轻卡那霉素的耳毒性,为耳毒性抗生素致聋的防治提供了一条新的研究途径。     

Identification of an intracellular pathway of thyroxine synthesis by dispersed thyroid cells

This study deals with the identification of the biochemical events involved in the metabolic sequence leading from the synthesis to the release of thyroxine in the dispersed thyroid cell system. (1) Using an experimental model allowing the differentiation between intracellular and extracellular sites of iodination, it is shown that thyroxine is synthesized inside the cells by an iodinating system sensitive to thyrotropin stimulation. (2) The secretion of thyroxine synthesized inside the cells is not mediated by an exocytotic-endocytotic phenomenon. Colchicine, vinblastine, fluoride, propanolol and chlorpromazine, at concentrations equal to or 10–100-times higher than those required to inhibit hormone release in follicular-organized thyroid tissue have no effect on thyrotropin-stimulated thyroxine secretion. (3) The secretion involves the intracellular proteolysis of hormone-containing iodoprotein(s) which, in addition to free thyroxine, generates free mono- and diiodotyrosines. Free thyroxine is released into the incubation medium and iodotyrosines are deiodinated under normal conditions and accumulate in the presence of an inhibitor of iodotyrosine deiodinase: 3,5-dinitrotyrosine. This proteolysis is inhibited by 5 mM chlorpromazine. These data indicate that the complete metabolic sequence leading from the uptake of iodide to the release of free thyroxine into the incubation medium can be described as an ‘intracellular metabolic sequence for thyroxine synthesis’.     

哺乳动物季节性繁殖的内源年生物钟及光敏神经环路研究进展

生活在温带和寒带的哺乳动物在长期的进化过程中形成了季节性繁殖的生活史特征。哺乳动物的繁殖功能主要受到下丘脑-垂体-性腺轴(hypothalamic-pituitary-gonadal axis,HPGA)的调控。视交叉上核(suprachiasmatic nucleus,SCN)能够自发振荡并响应光周期信号的变化,引发褪黑素分泌的改变,并介导下游通路中下丘脑甲状腺激素、Kisspeptin和RF酰胺相关肽(RF amide-related peptide,RFRP)的节律性表达变化,从而调控哺乳动物的季节性繁殖。本文综述了哺乳动物季节性繁殖的内源年生物钟调控,并强调了光敏通路中包括甲状腺激素、Kisspeptin和RFRP在季节性繁殖调控中的重要作用。     

Hypothyroidism in reproductively inhibited prairie deer mice (Peromyscus maniculatus bairdi) from laboratory populations

Several thyroid function parameters were compared between reproductively inhibited prairie deer mice of both sexes taken from laboratory populations and corresponding reproductively capable controls. The results of these experiments indicated the following: 1) prairie deer mice females had a statistically significant daily variation in mean serum thyroxine concentration and males displayed a similar trend; 2) total serum thyroxine and triiodothyronine were significantly lower in both male and female reproductively inhibited population animals compared with reproductively capable controls; 3) several morphometric characteristics of the thyroid of male and female population prairie deer mice were significantly different from that of control males and females, suggesting functional hypothyroidism in both sexes; 4) thyroid histology of male population deer mice was different from that of female population animals. In males, the data suggested that thyroid-stimulating hormone (TSH) stimulation was deficient due to some undetermined secondary hypothyroidism. In females, reduced serum thyroxine and triiodothyronine concentrations were observed due to primary hypothyroidism of unknown origin. The interrelationship between thyroid and adrenal function is discussed here and it is concluded that each of the systems may contribute to the observed reproductive inhibition. In particular, it was noted that the mechanism of response between population males and females may be quite different. No conclusive data are available to suggest whether one or the other system is the primary controller of the reproductive inhibition.     

Environmental and hormonal control of vernal migration in redheaded bunting (Emberiza bruniceps)

This paper reviews the factors and mechanisms which result in the development of the metabolic state characteristic of migration with special reference to a palaeotropic migrant the redheaded bunting,Emberiza bruniceps. Changes in climatic conditions and food supply act as proximate triggers of migratory behaviour in partial migrants. Typical migrants like buntings use daylength as a cue but the exact mechanism of how photoperiodic information is translated in terms of migratory events is still not known. Almost entirely the photoperiodic effects have been explained on the basis of the involvement of hypothalamo/hypophyseal system. We feel mechanism(s) other than those acting through neuroendocrine system may be equally important. Furthermore the role of temperature has not been adequately explored so far. Our observations indicate the possibility that redheaded buntings might integrate the information received from photoperiod with environmental temperature (and other factors?) resulting in the development of migratory state. The physiological control of avian migration is much less understood. Majority of papers have centered around the ‘gonadal hypothesis’ of Rowan supporting or contradicting it without providing conclusive evidence. Pituitary prolactin has also been shown to be implicated although the mechanism of action is only speculative. Conclusive evidence for the involvement of thyroid hormones (thyroxine, T4; triiodothyronine, T3) in the physiological timing of migration has been produced attributing independent roles to T4 and T3. It is suggested that seasonal variation in peripheral conversion of T4 to T3 could serve as an effective strategy to render available the required thyroid hormones T4 and/or T3 during different phases of the year thus accounting for the metabolic switch over from T4-dependent moult to T3-dependent migratory fat deposition and zugunruhe and also ensuring preclusion of simultaneous occurrence of these mutually incompatible events. Considering that the number of environmental and physiological factors influence this mechanism and considering that thyroid hormone molecule has been put to a wide range of usage during the course of evolution the mechanism(s) of peripheral conversion of T4-T3 may assume great flexibility and have selective value-especially in migration which is known to have evolved several times in diverse avian families. The attractiveness of this hypothesis lies in the fact that it has potential to explain the both physiological development of the metabolic state of migration and at the same time the physiological timing of migration not only with respect to the cycle of environment but also with respect to other conflicting seasonal events (moult and reproduction).     

A singular case of Graves' disease in congenital thyroid hemiagenesis

We report the observation of an unusual case of Graves' disease associated with thyroid hemiagenesis. A 41-year-old woman who presented with symptoms and clinical signs of hyperthyroidism was discovered to have thyroid hemiagenesia of the left lobe. Thyroid ultrasound scan showed enlargement of the right lobe with a single nodule, and absence of the left lobe; isotope scan showed homogeneous uptake in the single lobe and nodule. Ophthalmopathy, which was absent at presentation, developed after two years; after a further 2 years the patient developed decompensated hypothyroidism requiring thyroxine replacement. This is the first case of Graves' disease in thyroid hemiagenesis evolved to hypothyroidism, and a rare case of thyroid ophthalmopathy accompanying this condition.     

An investigation of the prolactin-thyroxine synergism in newt limb regeneration

The use of hormone replacement to support limb regeneration in hypophysectomized newts has been the subject of many investigations. Growth hormone, as well as prolactin (PL) in combination with exogenously supplied thyroxine, have all been shown to he effective. However, the bovine growth hormone used to support limb regeneration was contaminated by prolactin and thyroidstimulating hormone (TSH). The present investigation evaluates the significance of (1) prolactin contamination and (2) endogenous thyroxine synthesis resulting from TSH contamination on limb regeneration in hypophysectomized newts. The effect of supplying exogenous thyroxine was also evaluated. Our studies showed that when hypophysectomized newts were injected with contamination levels of PL and TSH, regeneration occurred, suggesting that the newt's thyroid synthesized sufficient thyroxine to support a prolactin-thyroxine synergism. The endogenous thyroxine was synthesized by thyroid glands that were indistinguishable from those of saline-injected, hypophysectomized controls.     

Structure of the thyroid gland, serum thyroid hormones, and the reproductive cycle of the Atlantic stingray, Dasyatis sabina.

This study examines the role of the thyroid gland in the control of reproduction in the viviparous Atlantic stingray, Dasyatis sabina. Thyroid activity in individuals in different reproductive stages was assessed both by microscopic examination of the gland, and by analysis of circulating levels of thyroid hormones from the same individuals. The thyroid gland is a cylindric organ, embedded in a connective tissue capsule, and composed of follicles, i.e., monolayer spheres of thyroid epithelial cells. Stingray follicular cells possess several characteristic features, namely apical cilia and a well-developed endoplasmic reticulum. Cells vary in size and shape, according to the activity of the gland. No structural differences were observed between the thyroid glands of the two sexes. Both thyroid hormones, triiodothyronine, [T(3)], and thyroxine, [T(4)], were detected in the serum of all animals examined. Levels ranged from 1.3-2.6 microg/100 ml for total T(4), and from 1.2-2.6 ng/ml for total T(3). The T(4) levels did not vary significantly in any group. Immature individuals and females undergoing oogenesis had the lowest levels of circulating T(3) and mature females from ovulation throughout gestation had high thyroid gland activity and high levels of circulating T(3). J. Exp. Zool. 284:505-516, 1999.     

Hormonal regulation of thermogenesis in goslings. Possible role of the thyroid gland.

The experiments performed on 90 male goslings showed that 6 h cold exposure (5 +/- 1 degree C) of the specimens 3, 10 and 21-day-old increases considerably 131I uptake by their thyroid gland. After single subcutaneous injection of thyroxine (100 mug/kg) no significant alterations of the metabolic rate, during 4 h measurements, in comparison with the pre-injection value were observed. Since, in control birds about 17% decrease of the metabolic rate within the same time occurred, as the effect of fasting, it was concluded that thyroxine does have the calorigenic effect. The metabolic rate of the goslings 5 to 7-day-old treated with thyroxine for four consecutive days (100 mug/kg daily) and the control ones was very similar. In the older goslings (22--24 days) thyroxine treatment significantly elevated the metabolic rate. Direct (extrathyroid) effect of TSH on heat production, did not occur in goslings.     

Response of the interrenal to adrenocorticotropic hormone after short-term thyroxine treatment of coho salmon (Oncorhynchus kisutch)

The effects of experimentally elevated plasma thyroxine levels on the subsequent response of interrenals of coho salmon (Oncorhynchus kisutch) to adrenocorticotropic hormone (ACTH) in vitro were examined. Animals were treated with thyroxine by immersion (200 micrograms/L) for 3 days, which resulted in physiological elevations in circulating thyroxine. In animals treated before the parr-smolt transformation was completed (early smolts), thyroxine had no effect on plasma cortisol levels but significantly enhanced the sensitivity of the interrenal to ACTH in vitro. In animals treated after the period of smoltification (postsmolts), plasma cortisol levels were significantly higher than those of controls; both experimental and control animals had plasma cortisol levels higher than normally observed at this stage of development. The response of the interrenals of thyroxine-treated postsmolts to ACTH in vitro was significantly lower than that of controls. Results from the experiments using early smolts are in agreement with studies in other vertebrates showing that thyroid hormones are involved in maintaining the normal functioning of corticosteroidogenic tissue and suggest that thyroid hormones may be involved in the activation of the interrenal that occurs during smoltification. The results obtained using postsmolts are more difficult to interpret because of the possibility that these animals were physiologically stressed by the treatment. Increased ACTH release in vivo resulting from stress may have led to a depression of interrenal sensitivity to ACTH in vitro and may have masked a refractoriness of the pituitary-interrenal axis to thyroxine.     

Thyroid hormone replacement normalizes renal renin and angiotensin receptor expression in thyroidectomized fetal sheep

Previous studies have suggested that thyroid hormone influences maturation of the renin-angiotensin system (RAS) and cardiovascular function in the late-gestation fetal sheep. To further examine the importance of thyroid hormone in this regard, we used the technique of thyroidectomy (TX) to remove endogenous thyroid hormone from the circulation and then replaced it with physiological amounts of exogenous thyroxine. We hypothesized that the previously observed changes in RAS activity and cardiovascular function associated with TX would be normalized. TX was performed at 120 days of gestational age (dGA), and control fetuses were sham operated. After 3 days of recovery, TX fetuses were continuously intravenously infused with thyroxine until delivery by cesarean section close to term (around 138 dGA). Immediately before necropsy, fetuses were infused with isoproterenol, and the hemodynamic responses were noted. Thyroid hormone replacement normalized not only plasma triiodothyronine (T3) and thyroxine (T4) levels but also the TX-induced decreases in renal renin mRNA and renal renin content. Renal ANG II subtype receptor expression levels were also normalized for both mRNA and protein. Decreased basal heat rate and systolic blood pressure associated with TX returned to normal following replacement; however, changes in mean blood pressure and isoproterenol-induced changes in mean blood pressure were not altered. These findings demonstrate that replacement of thyroid hormone in hypothyroid sheep fetuses can restore renal ANG II receptor and renin expression and secretion to normal.     

Reduced serum free thyroxine concentration in postmenopausal women receiving oestrogen treatment.

Thyroid hormone state was assessed in a group of postmenopausal women who had received long term treatment with oestrogen. Serum concentrations of total thyroxine, triiodothyronine, and thyroxine binding globulin were raised compared with those in a control group given placebo; serum concentrations of thyroid stimulating hormone did not differ between the groups. Oestrogen treatment resulted in a significant decrease in the serum free thyroxine concentration and in the ratio of thyroxine to thyroxine binding globulin, which supports the view that oestrogen is the causative factor of the physiological reduction in free thyroid hormone during pregnancy.     

Evidence for a secretion of thyroxine by isolated hog thyroid cells.

Isolated thyroid cells prepared from hog thyroid glands by tryptic dispersion were incubated with 131I- for 1--6 h. Free [131I]thyroxine was identified in the incubation medium by three chromatographic methods. Neither [131I]iodotyrosines nor [131I]triiodothyronine were detected. The [131I]thyroxine released in the medium by 100 mul of cells (packed cell volume) after a 6-h incubation period amounted to 1.16% (S.E. = +/- 0.39) of the total radioactivity. The medium [131I]thyroxine represented 15--25% of the total [131I]thyroxine synthesized during the 6 h of incubation. Thyrotropin, 1--60 munits/ml, increased the medium [131I]thyroxine content 2-4 fold. Dibutyryl cyclic AMP mimicked the effect of thyrotropin. The amount of medium [131]thyroxine was strictly related to the amount of incubated cells but was independent of the volume of the incubation medium. When prelabeled cells were incubated in the presence of methimazole the increase in medium [131I]thyroxine was quantitatively related to a decrease in the intracellular [131I]thyroxine. Addition of dinitrotyrosine, an inhibitor of the deiodinase activity, induced the release of iodotyrosines in the incubation medium. That the incubation supernatant of isolated thyroid cells did contain free thyroxine but not iodotyrosines suggests that the normal mechanisms of proteolysis of thyroglobulin and deiodination of iodotyrosines inside the cells are preserved. From these data, it was concluded that the thyroxine release by isolated cells represents a real secretion.     

Thyroid hormone levels in the peripheral blood of the ground squirrel Citellus parryi during winter hibernation

In the Arctic ground squirrel Citellus parryi, thyroxine and triiodothyronine concentrations in the peripheral blood have been determined by RIA in various seasons and during a short hibernation period. It was shown that during hibernation (December-February), hormonal concentration is higher than during homoiothermal period (August-October). The highest concentration of the thyroid hormones was found in hibernating animals in January. The data obtained indicate that thyroid hormones are involved in control of hibernation of the species investigated.     

Serum-thyroxine levels in microwave-exposed rats

The nature of the response of the thyroid gland in animals exposed to microwave irradiation is controversial. An enlarged thyroid and an increase of radioiodine uptake in microwave workers have been reported. Absence of thyroid disorders has also been reported in other exposed populations. Animal experimentation has contributed to the controversy because both increased and decreased thyroid functions have been reported. The thyroxine concentration in rats as representative of thyroid function in animals exposed to 2.45-GHz, 120-Hz amplitude-modulated microwaves has been studied. Comparison was made between thyroxine concentrations in microwave- and sham-exposed rats by Student's t test. After a 1-hr exposure, an increased thyroxine concentration was found in rats exposed at 40 and 70 mW/cm2, but not at 1, 5, 10, 20, 50, or 60 mW/cm2. After a 2-hr exposure, increased thyroxine concentration was noted in rats exposed at 25, 30, and 40 mW/cm2, but not at 1, 5, 10, and 20 mW/cm2. After a 4-hr exposure, thyroxine concentration increased in rats exposed at 1 mW/cm2 and decreased in rats exposed at 20 mW/cm2; but changes were not noted at 5 or 10 mW/cm2. Other experiments included animals that were exposed once for 4 hr (0.1, 1, 10, 25, and 40 mW/cm2), sampled 24 hr after a 4-hr exposure (0.1, 1, 10, 25, and 40 mW/cm2), or exposed for 4 hr 3 times (1, 10, 20, 30, 40, and 55 mW/cm2) and 10 times (1, 10, 20, 25, 30, and 40 mW/cm2), to evaluate the consistency of the thyroxine response. None of the rats in these experiments displayed any alteration of thyroxine concentration, except that decreased thyroxine was noted in rats exposed at 40 mW/cm2 for the third time. These studies covered a long time span; rats from two commercial sources (BS and CR) were used and subjected to different numbers of exposures, and therefore these data were evaluated for their stability. Two factors could influence the result significantly, i.e., source of animal and number of sham exposures. Rats used in the 2-hr exposures were from two different commercial sources; rats from CR had a higher (but normal) thyroxine concentration than did rats from BS. Therefore the data of these animals were separated by commercial source for reevaluation. Instead of increased thyroxine concentration in rats exposed at 25, 30, and 40 mW/cm2, changes were not noted in any microwave-exposed rats. The influence of sham exposure revealed that appropriate concurrent control and specification of animal source are needed in longitudinal studies.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neonatal screening for congenital hypothyroidism by measurement of plasma thyroxine and thyroid stimulating hormone concentrations.

Neonatal screening for congenital hypothyroidism was introduced in the City of Birmingham in 1980 by measuring concentrations of both thyroid stimulating hormone and thyroxine in plasma. Over two years 30 108 babies were tested. Thirty one babies were recalled because of thyroid stimulating hormone concentrations greater than 40 mU/l, of whom 12 were treated with replacement thyroxine. Six babies were found to have low thyroxine concentrations because of reduced thyroxine binding globulin and five raised thyroxine values because of increased thyroxine binding globulin. As a result of this study screening was continued with measurement of thyroid stimulating hormone only as the primary test for congenital hypothyroidism, the thyroxine value being measured only when the concentration of thyroid stimulating hormone exceeded 20 mU/l.     

Thyroid hormone stimulation of lipolysis and cyclic adenosine 3', 5'-monophosphate accumulation in human adipose tissue

The role of thyroid hormones on lipolysis in human subcutaneous adipose tissue was investigated. Incubation of subcutaneous fat pads with thyroxine (0.1--10 000 nM) augmented the subsequent isoproterenol stimulation of lipolysis, measured by glycerol release. The basal lipolysis could not by stimulated by thyroxine. The theophylline- and dibutyryl-cyclic AMP stimulated lipolysis also could not be increased by thyroxine at these concentrations. In separate studies, the effect of thyroxine (0.01 pM--1 microM) and triiodothyronine (0.01 pM--1 microM) on cyclic AMP accumulation was examined. No effect of thyroid hormones on cyclic AMP accumulation was seen in non-isoproterenol stimulated tissue. Fat pads stimulated by isoproterenol and then treated with thyroid hormones showed marked increases in accumulation of cyclic AMP as compared to control tissue in the presence of isoproterenol alone.