Pituitary Thyrotropin Research Articles

Symptomatic Hyperthyroidism in a Patient Taking the Dietary Supplement Tiratricol

An 87-year-old woman was referred for evaluation of nervousness, tremor, insomnia, and fatigue of 2 months' duration. Initial laboratory evaluation revealed a suppressed thyrotropin level and an elevated triiodothyronine level. A review of her medications revealed that she had started taking several dietary supplements at the recommendation of her chiropractor before the onset of symptoms. One of these was tiratricol (3,5,3'-triiodothyroacetic acid or Triac), a substance sold as a dietary supplement despite classification as a drug by the Food and Drug Administration. Tiratricol has weak thyromimetic effects, can inhibit pituitary thyrotropin secretion, and in higher doses can significantly stimulate metabolism. Such was the case with this patient who presented with signs, symptoms, and biochemical evidence of hyperthyroidism that promptly resolved after discontinuation of tiratricol therapy. To our knowledge, this is the first reported case of documented thyrotoxicosis secondary to tiratricol use. Because tiratricol is still available for sale on several Internet sites, this case emphasizes the importance of inquiring about the use of dietary supplements in all patients. The availability of such products on the Internet increases the already complex task of monitoring patients' use of dietary supplements.

The thyroid axis just got more complicated

As a first-year medical student, you could count on the simplicity and elegance of the thyroid axis, because all its details had apparently been elucidated. Hypothalamic thyrotropin-releasing hormone (TRH) promoted the synthesis, release, and glycosylation of pituitary thyrotropin, thyroid-stimulating hormone (TSH), which in turn acted on the thyroid follicle, leading to the synthesis and release of thyroid hormones (T4 and T3). Furthermore, precise control of the axis was maintained by thyroid hormone negative feedback at both the hypothalamic and pituitary levels (Figure ​(Figure1).1). Now, a new pituitary hormone, termed thyrostimulin, may change our established view of this axis. Figure 1 The role of thyrostimulin in the thyroid axis and periphery. Thyrostimulin, a heterodimeric glycoprotein hormone, is synthesized in the pituitary and other peripheral tissues. It is suggested to act in a paracrine fashion at these sites. A role for thyrostimulin ... TSH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and chorionic gonadotropin (CG) are a family of heterodimeric pituitary and placental glycoprotein hormones that share a common α subunit (1). Their biological specificity at either the thyroid or the gonad is conferred by a unique β subunit that is noncovalently linked to the common glycoprotein α subunit. All of these hormones have been purified by classical means, and their biological activities established by in vivo assays. Nakabayashi et al. in this issue of the JCI (2) describe a novel heterodimeric glycoprotein hormone containing two unique subunits, which they term A2 and B5. These investigators identified A2 and B5 in a homology search of the human genome (GenBank). In a nearly simultaneous paper in another journal, the same group describes orthologs of these subunits found in diverse species (3). A2 and B5 share only modest amino acid similarity with the related glycoprotein hormone subunit family members, but they contain all of the cysteine residues required to form the characteristic cysteine knot structure found in these and other growth factors, including PDGF and TGF-β. The authors show here that A2 interacts strongly with FSH-β, CG-β, and B5 in a yeast two-hybrid assay (2). After determining that the A2/B5 pair can stimulate cAMP production via the TSH receptor, Nakabayashi and colleagues pursued the thyrotropic activity of A2/B5 in greater detail.

Changes in Thyrotropin Messenger RNA and Circulating Hormone Levels during Induced Molting of the Hen (<i>Gallus domesticus</i>)

Levels of pituitary thyrotropin messenger RNA and circulating hormones during molting induced by feed and water deprivation were determined by reverse-transcription polymerase chain reaction and radioimmunoassays. Plasma levels of luteinizing hormone and estradiol decreased from the next day (Day 1), and progesterone from Day 3, of deprivation treatment, and were associated with the cessation of egg laying on Day 4. The plasma thyroxine level of experimental hens increased on Day 5 and remained high until Day 17, whereas the plasma concentration of triiodothyronine was lower than the control level throughout the experimental period. The messenger RNA level of the pituitary thyrotropin β subunit of experimental hens decreased markedly at first, but then increased showing a peak on Day 3 followed by a gradual decrease until Day 17. The serum prolactin level decreased on Day 3 and remained low until Day 17. These results suggest that (1) a decline in hormones associated with egg laying is followed by activation of the pituitary-thyroid axis, (2) thyrotropin triggers the increase in thyroxine but is not necessarily responsible for the maintenance of the high thyroxine level, and (3) prolactin might be involved in molting induced by feed and water deprivation.

Functional Sensitivity and Recovery of Thyroid-stimulating Hormone

Comparisons of the Vitros ECi thyroid-stimulating hormone (TSH) method with the AxSym (1), Immulite (1)(2), Elecsys (2), and ADVIA Centaur (2) have shown an unexplained progressive negative bias <0.2 mIU/L, a phenomenon that we have also observed (Fig. 1A⇓ ). To investigate the bias, we diluted the TSH International Reference Preparation 80/558 (predominately pituitary TSH) and serum from a patient with untreated hypothyroidism (a mixture of pituitary and hepatic sialylated TSH) in serum pooled from patients receiving suppressive doses of thyroxine for thyroid cancer and with undetectable TSH values by the ADVIA ACS:180, Vitros ECi TSH, and Roche Elecsys methods. To obtain accurate dilutions at …

Autoimmune hypothyroidism coexisting with a pituitary adenoma secreting thyroid-stimulating hormone, prolactin and α-subunit

Autoimmune hypothyroidism coexisting with a pituitary adenoma secreting thyroid-stimulating hormone, prolactin and α-subunit

Molecular cloning of cDNA encoding thyroid stimulating hormone β subunit of bighead carp Aristichthys nobilis and regulation of its gene expression

The complementary DNA (cDNA) encoding pituitary thyroid stimulating hormone beta subunit (TSH-β) of bighead carp was cloned and regulation of its gene expression was investigated for understanding phylogenetic divergence and evolution of TSH molecule. The cDNA was obtained from bighead carp pituitary total RNA by reverse transcription and polymerase chain reaction. Oligonucleotide primers were designed from the sequence of common carp. The full length sequence was then obtained by 3′ and 5′ rapid amplification of cDNA ends (RACE). The full-length sequence consisting of 3′ and 5′ untranslated regions was 585 bp long. The predicted amino acid sequence consisted of a signal peptide of 19 amino acid residues and a mature TSH β subunit protein of 131 residues. The coding sequences of the cDNAs showed variable percentage homologies with those of other teleosts and vertebrate species. The predicted amino acid sequence shared 71% identity with rainbow trout and salmon, 90% with goldfish, 50% with eel and 94% with common carp in the mature protein region. The percentages of identity in the same region in comparison with bovine, porcine, rat, mouse, human and chicken were only 39, 42, 41, 40, 45 and 46%, respectively. TSH β mRNA expression was found only in the pituitary tissue out of other tissues tested as testis, muscle, brain and heart. For the first time, thyrotropin releasing hormone (TRH) and thyroxine (T 4) effects on pituitary TSH mRNA expression were tested in teleosts under in vitro conditions. TRH treatment on pituitary cells increased TSH β mRNA level, while T 4 treatment decreased TSH β mRNA level. The present study provides a direct evidence, for the first time that TRH directly upregulates TSH β gene expression in teleosts.

Localization of endothelin A receptors in the rat pituitary TSH cells: light- and electron-microscopic immunohistochemical studies.

Endothelins modulate hormonal secretion in the pituitary gland. Intense signaling of endothelin A receptors (ET(A)R) has been detected by in situ hybridization, binding assay and receptor autoradiography. We used light- and electron-microscopic immunohistochemistry of ET(A)R with polyclonal antibody against a synthetic peptide corresponding to the carboxyl terminus (403-427) of human ET(A)R. Immunoreactivity was observed in 6-8% of anterior pituitary cells, which were rather large polygonal or stellate cells. These cells were often clustered. Double-staining immunofluorescence showed that the ET(A)R-positive cells immunoreacted with antibody against the beta-subunit of thyroid-stimulating hormone (TSH), but not adrenocorticotropic hormone (ACTH) or lutenizing hormone beta (LHbeta). Pre- and postembedding electron-microscopic immunohistochemistry showed that ET(A)R-positive cells had vacuolated or parallel-lined rough endoplasmic reticulum (rER) and numerous round granules in their periphery and the elongated processes. By pre-embedding immunohistochemistry, diaminobenzidine tetrahydrochloride (DAB) products were shown to be mostly located around the granules and occasionally underneath the plasma membrane. By postembedding immunohistochemistry, granules in the ET(A)R-positive cells were 90-150 nm in diameter, and colloidal gold particles due to ET(A)R were associated with about 10% of these granules. These results indicate that ET(A) receptors are associated mostly with the secretory granules of TSH cells.

The thyrotropin receptor is not involved in the activation of p42/p44 mitogen-activated protein kinases by thyrotropin preparations in Chinese hamster ovary cells expressing the human thyrotropin receptor.

We studied whether bovine pituitary thyrotropin (bTSH) or human recombinant thyrotropin (rhTSH) stimulated p42/p44 mitogen-activated protein kinases (MAPKs) in Chinese hamster ovary cells expressing human thyrotropin receptor (CHO-hTSHR cells). We show that p42/p44 MAPK phosphorylation was induced by both TSH preparations at similar levels in CHO-hTSHR cells and in wild-type CHO cells. In contrast, cyclic adenosine monophosphate (cAMP) production was stimulated by TSH only in CHO-hTSHR cells, demonstrating that p42/p44 MAPK stimulation was independent of the TSH receptor. Moreover, similar results were obtained with two other cell lines: the FRTL-5 thyroid cell line and the CCL39 fibroblast cell line. Maximal stimulation of p42/p44 MAPK phosphorylation was observed after a 5- to 10-minute incubation with bTSH and rhTSH preparations. At this time, the phosphorylation of GST-Elk1 was also increased in a time- and concentration-dependent manner by bTSH preparations. The phosphorylation of p42/p44 MAPKs was abolished by PD 98059 and GF 109203X, indicating the involvement of MAPK kinases (MEK 1/2) and protein kinase C. In contrast, the activation of p42/p44 MAPKs was insensitive to H89, to cholera toxin and to pertussis toxin. These data suggest that the protein kinase A pathway was not implicated in p42/p44 MAPK activation by TSH preparations. Moreover, Gs or Gi/Go proteins do not appear to participate in p42/p44 MAPK activation. We also showed that these TSH preparations failed to induce activation of c-Jun NH2 terminal kinase. We therefore conclude that the commercial TSH preparations used in this study contained factor(s) responsible for the specific activation of p42/p44 MAPKs by a TSH receptor-independent mechanism.

The use of X-ray fluorescence determination of the concentration of intrathyroid iodine in thyroidology

The results of 7-year utilization of a Russian analyzer for noninvasive x-ray fluorescent measurement of intrathyroid stable iodine for diagnosis and monitoring the treatment efficiency in patients with thyroid diseases are analyzed. A total of 400 adults (130 men and 270 women) aged 20-50years and 67children (12 boys and 55 girls) aged 5-16 years with various thyroid diseases were examined. Control group consisted of 60 women and 30 men without thyroid diseases (according to clinical and laboratory studies). Ultrasonography and scintigraphy of the thyroid, measurements of the blood pituitary thyrotropic hormone, thyroid hormones, antibodies to thyroglobulin and thyroid peroxidase, cytological and h istological studies, and a new method for thyroid iodine measurements were used.&#x0D; The results indicate the need in a new diagnostic method based on analysis of intrathyroid iodine. Such a method is needed for 1) prophylactic screening of population, including children, pregnant and nursing women in order to detect (with an accuracy of 7095%) subjects with suspected autoimmune thyroid diseases; 2) accurate evaluation of the degree of thyroid involvement in autoimmune thyroiditis and identification of the pathogenesis of hypothyrosis or thyrotoxicosis; 3) monitoring the efficiency of treatment with iodides, thyroxin, and their combinations and for thyroid function recovery after mercazolil therapy of diffuse thyroid goiter; and 4) differential diagnosis of benign and malignant thyroid diseases.

Evaluation of the effectiveness of treatment with thyroxine and iodotyrox drugs in patients with diffuse non-toxic goiter in Moscow

The efficiency of therapy with a combined thyroxin-iodine drug and monotherapy with thyroxin was compared in patients with diffuse nontoxic goiter (DNG), and the effect of iodine intake was evaluated. The study was carried out in an outpatient setting by the double blind method in 46 women aged 18-50 years with DNG: 22 were treated by the combined drug (TI) containing 100 pg L-thyroxin and 100 pg potassium iodide per tablet (lodthyrox, Merck KGaA) and 24 were treated by thyroxin (T) in a dose of 100 pg (Euthyrox, Merck KGaA). The treatment was administeredfor 1 year. A year after this treatment, 15 women were treated with iodinated oil (IO) (lipidol capsules, Guerbet) containing 380 mg iodine. Thyroid volume, concentrations of intrathyroid stable iodine (ISI), pituitary thyrotropic hormone, free triiodothyronin and thyroxin, and antibodies to thyroglobulin and thyroid peroxidase in the blood were evaluated in all women before and during treatment.&#x0D; Therapy with T and TI equally decreased the size of the thyroid in DNG. ISI concentration decreased during TI treatment less than during monotherapy. Thyroid volume increased to the pre-treatment size 12 months after therapy with T or TI was discontinued, while ISI concentration remained lowered. Administration of IO led to a decrease in the thyroid size, less pronounced than during T or TI treatment, and to an increase in ISI concentration.

The Hyperthyroid Fetus and Infant

After completing this article, readers should be able to: 1. Describe the etiology of transient and persistent neonatal hyperthyroidism. 2. Delineate the diagnostic tests for thyroid-stimulating hormone receptor antibodies. 3. Develop a treatment plan for fetal and neonatal hyperthyroidism and a management plan for subsequent pregnancies. 4. Provide guidelines for breastfeeding when the mother is receiving antithyroid medications. 5. Describe the long-term risks of neonatal hyperthyroidism. The first clinical description of neonatal hyperthyroidism was published in 1912, and the discovery of the transplacental passage of thyroid-stimulating immunoglobulins (TSI) provided an understanding for the etiology of this condition in 1964. There were, however, a few cases of persistent neonatal hyperthyroidism, initially described in 1976, that were inconsistent with the transient clinical course expected with a maternally acquired antibody. The etiology of persistent neonatal hyperthyroidism was clarified by the discovery of an activating germ-line mutation in the thyroid-stimulating hormone (TSH) receptor in 1995. When a mother has autoimmune thyroid disease, fetal and neonatal hyperthyroidism result from transplacental passage of TSI. The mother usually has a history of hyperthyroidism, but neonatal hyperthyroidism also has been reported in mothers who have hypothyroidism due to Hashimoto thyroiditis. The clinical status of the mother does not determine the infant’s risk for hyperthyroidism. The mother may have been treated with 131I or a subtotal thyroidectomy in the past and may be euthyroid or she may be receiving thyroid replacement therapy at the time of her pregnancy, but she still can be producing high titers of TSI. In a review of neonatal hyperthyroidism, mothers were clinically hyperthyroid during pregnancy in only 18 of 38 cases (47%). The prevalence of clinical hyperthyroidism in pregnancy has been reported to be 0.1% to 0.4% and is the most common endocrine disorder during pregnancy after diabetes. Clinical fetal and neonatal hyperthyroidism has been reported to occur …

Leptin, nutrition, and the thyroid: the why, the wherefore, and the wiring

The function of the thyroid gland is to produce the thyroid hormones T3 and T4, which regulate gene transcription throughout the body (1). In medical practice, the thyroid becomes an issue when its size or shape becomes abnormal or when it produces too much or too little hormone. Thus, we typically think of the thyroid with reference to the clinical states of goiter, or hyper- or hypothyroidism. But what is the physiology of the thyroid when the gland and the entire hypothalamic-pituitary-thyroid axis are intact? As first year medical students ask each year, Why exactly do we have a thyroid, at all?

Morphology of FRTL-5 cell colonies in a semi-solid medium.

For the first time, 3, 7 and 10 days growth of normal thyroid follicular FRTL-5 cell colonies in a semi-solid medium of 0.6% methocel over 1% agar base was morphometrically analyzed. It was found that the areas of FRTL-5 colonies as well as their perimeters and maximum diameters increased, while according to their form factors the FRTL-5 colonies were regular in shape. After 10 days in a semi-solid medium, 83% of the FRTL-5 colonies had maximum diameters greater than 50 microm. It is obvious that after long culturing of FRTL-5 cells under the influence of the pituitary thyroid-stimulating hormone (TSH) these cells are not uniform anymore and that they grow in a semi-solid medium.

Comparison of Pituitary and Recombinant Human Thyroid-stimulating Hormone (rhTSH) in a Multicenter Collaborative Study: Establishment of the First World Health Organization Reference Reagent for rhTSH

The increasing use of recombinant-DNA-derived materials in therapy and diagnosis poses a new challenge for biological standardization, that of developing reference preparations appropriate for both the native and recombinant products. Here we report the results of an international collaborative study that was carried out under the auspices of WHO to assess the suitability of a preparation of recombinant thyroid-stimulating hormone (rTSH; 94/674) to serve as a potential standard for the calibration of diagnostic immunoassays compared with the International Reference Preparation (IRP) for human TSH (80/558). Coded samples were provided to the 33 laboratories in the study, and participants were asked to perform TSH assays currently in use in their laboratories. Twenty-eight laboratories contributed 93 immunoassays in 41 different method-laboratory combinations, and an additional 5 laboratories contributed bioassay data. All data were analyzed centrally at the National Institute for Biological Standards and Control. The results obtained in different laboratories and with different assay systems revealed significant variability between estimates of rTSH relative to the IRP. These ranged from 5. 51 mIU (95% limits, 3.95-7.67 mIU) per ampoule by RIA to 7.15 mIU (95% limits, 6.7-7.63 mIU) per ampoule by immunofluorometric assay. However, the results showed that the assignment of a value of 6.70 mIU per ampoule of 94/674 would give reasonable continuity with the IRP in many assay systems. The preparation was established as the First WHO Reference Reagent for TSH, human, recombinant, to provide a means of validating assay performance and to maintain continuity with the IRP without compromising clinical data.

Changes in thyroid gland morphology after acute acrylamide exposure.

High exposure to the acrylamide monomer has been associated with neuropathy and neurotoxic effects. Chronic lower exposure causes endocrine disruption associated with thyroid, testicular, and mammary tumors. To investigate mechanisms of endocrine disruption, short-term, low-level oral dosing studies were conducted. Weanling female Fischer 344 rats were acclimatized for two weeks before dosing. Controls were given distilled water by gavage and rats in other groups were given acrylamide at doses of 2 mg/kg/day and 15 mg/kg/day for 2 or 7 days by gavage. Twenty-four h after the last dose, the rats were killed by decapitation. Trunk blood was collected for hormone analyses and tissues for histopathological examination. There were no toxicity-related deaths, no clinical signs of toxicity, and no significant difference in the mean body weight of animal groups. Histopathological examination of select tissues showed no lesions of pathologic significance. Plasma thyroxine (T4), thyroid stimulating hormone (TSH), prolactin (PRL), and pituitary TSH and PRL analyses did not reveal significant changes between control vs. treated rats. In the 7-day study, however, there was a slight dose-dependent increase in plasma T4 and a slight dose-dependent decrease in plasma TSH. Thyroid gland morphometry showed a significant (p < 0.05) decrease in the colloid area and a significant increase (p < 0.05) in the follicular cell height of treated rats as compared to controls. The follicular area shrinkage was similar in both studies. These results show a very early endocrine response to very low levels of toxic insult and opens other venues to further investigate the mechanisms of endocrine disruption by acrylamide.

Effects of acute exposure to PCBs 126 and 153 on anterior pituitary and thyroid hormones and FSH isoforms in adult Sprague Dawley male rats

3,3'4,4',5-Pentachlorobiphenyl (PCB 126) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) were administered to adult male rats in order to identify sensitive indicators of endocrine disruption. We tested the hypothesis that PCB exposure modifies follicle-stimulating hormone (FSH) pituitary isoforms, as well as the pituitary and serum concentrations of FSH, luteinizing hormone (LH), growth hormone, prolactin, and thyroid-stimulating hormone (TSH). Effects on serum levels of thyroxine (T4) and testosterone (T), and prostate androgen receptor content, were also tested. In one experiment, 5 groups of 8 rats each received two i.p. injections, one day apart, of either corn oil or 6.25, 25, 100 or 400 micrograms/kg/day of PCB 126. Decreases (p < 0.05) in the serum concentrations of T4 and LH started at doses of 25 and 100 micrograms/kg/day, respectively. Serum FSH concentrations were reduced (p = 0.07) in the highest dose group. In contrast, pituitary content of FSH and LH increased with PCB-126 doses (p = 0.004, p = 0.002, respectively). Despite changes in reproductive hormones, PCB-126 had no effect on the androgen receptor content of the prostate. The effect of PCB-126 was tested in the hemicastrated rat, and suggested adverse effects on testosterone secretion. To test the effects of PCB exposure on FSH pituitary isoforms, 4 groups of 10 male rats received two i.p. injections, one day apart, of either corn oil, PCB 153 (25 mg/kg/day), estradiol-17 beta (E2; 20 micrograms/kg/day), or PCB 126 (0.1 mg/kg/day). Serum T4 levels were higher (p < 0.01) in the E2 and PCB 153 groups, and slightly reduced in the PCB 126-treated groups, compared to controls. Simultaneous purification of pituitary FSH and TSH isoforms was performed by HPLC, using two chromatofocusing columns in series. In contrast to TSH isoforms, the distribution of FSH isoforms over the chromatography run differed slightly between treatment groups; the amounts of FSH isoform eluted during the pH gradient were lower (p < 0.05) in E2 and PCB 153-treated rats than in control or PCB 126-treated rats. The similarity between the effects of E2 and PCB 153 on T4 and FSH isoforms supports the contention that PCB 153 possesses estrogenic properties. Serum LH and T4 concentrations were the most sensitive and practical endocrine indicators of PCBs 126 and 153 exposure in male rats.

Thyroid hormones down-regulate thyrotropin β mRNA level in vivo in the turbot (Psetta maxima)

Thyroid stimulating hormone (TSH) is a vertebrate pituitary heterodimeric hormone that stimulates the thyroid gland to produce the thyroid hormones, T3 and T4. We report here the cloning, by PCR on reverse-transcribed pituitary RNAs, of a 180 bp fragment of the cDNA encoding TSH β subunit in the turbot (Psetta maxima). The deduced amino acid sequence displayed 66 and 75% identity with the corresponding sequence from the European eel (Anguilla anguilla) and the rainbow trout (Oncorchyncus mykiss), respectively. This cDNA was then used as a probe for densitometric analysis of individual pituitary Northern blots. TSH β mRNA levels were quantified in turbot where circulating thyroid hormones were modified by dietary treatments or hormone supplementation. Recombinant rainbow trout growth hormone had no effect on circulating thyroid hormone levels or on pituitary TSH β mRNA level. In turbot fed heat-treated rapeseed meal, plasma T4 levels were lowered and TSH β mRNA increased more than two fold. In contrast, when turbot were fed a standard fish-meal supplemented with T3, circulating T3 levels were elevated and there was a dramatic decrease in TSH β mRNA level. It is concluded that both thyroid hormones are able to down-regulate TSH β mRNA level in vivo in the turbot. These results are discussed in the context of the evolution of the TH feed-back on TSH production.

A comparative review of the structure and biosynthesis of thyroglobulin

Thyroglobulin, the major iodoglycoprotein of the thyroid ( M r 669 kDa) has a sedimentation coefficient of 19 S and an isoelectric point (p I) of 4.4–4.7. The protein has been isolated and purified from saline extracts of the gland of several animal species, by methods such as ammonium sulfate fractionation, DEAE-cellulose chromatography and Sepharose 4B/6B gel-filtration. DEAE-cellulose chromatography of thyroglobulin from many species, by linear gradient, yielded a complex elution pattern, while camel thyroglobulin showed only a major and minor peak. As an iodoprotein, the protein has 0.1–2.0% iodine. The amino acid and iodoamino acid composition of thyroglobulins, in general, is similar. However, a high thyroxine content (15 mol/mol protein) has been noted for buffalo species. Asparagine or aspartic acid has been reported as the major N-terminal amino acid for thyroglobulins of several animal species whereas glutamic acid is the sole N-terminal amino acid for buffalo thyroglobulin. As a glycoprotein, thyroglobulin contains 8–10% total carbohydrate with galactose, mannose, fucose, N-acetyl glucosamine and sialic acid residues. The carbohydrate in the protein is distributed as two distinct units, A and B. In addition, human thyroglobulin has carbohydrate unit C. The occurrence of sulfate and phosphate as Gal-3-SO 4 and Man-6-PO 4, respectively, has been reported in few species. The quaternary structure of native thyroglobulin is comprised of two equal sized subunits of 330 kDa. However, the protein appears to contain 4–8 non-identical units in few species. The synthesis of thyroid hormones occurs in the matrix of the protein and is regulated by pituitary thyrotropin. The role of tyrosine residues 5 and 130 in thyroxine synthesis has been well documented.

A case of an autonomously functioning thyroid nodule associated with low triiodothyronine concentrations.

A 66-year-old woman with an autonomously functioning thyroid nodule (AFTN) showed low serum levels of triiodothyronine (T3) and no response of thyroid stimulating hormone (TSH) to thyrotropin releasing hormone (TRH). After administration of methimazole, TSH level increased from 0.1 to 19μ/U/ml. After surgical removal of the thyroid nodule, both TSH and T3 levels increased to normal and the response of TSH to TRH stimulation became normal. These findings suggest that the AFTN may be associated with low T3 concentrations and that certain substances released by the AFTN may be responsible for the inhibition of pituitary TSH response to TRH stimulation.

Are extant lungfish neotenic?

1. The thyroid axis in developing lungfish is being explored to ascertain whether it shows similar deficiencies to those characteristic of neoteny in urodele amphibians. 2. At hatching, the pituitary of Neoceratodus forsteri comprises a lumen surrounded by a single layer of epithelial cells lying immediately below the hypothalamus, but unconnected to it. Over the first year of development, the number of pituitary cells increases and several cell types, including thyrotropes, can be recognized immunocytochemically, but the pituitary remains unconnected to the hypothalamus. 3. By treating the lungfish with thyroid inhibitor, no increase in thyroid uptake of iodine, indicative of induced pituitary thyroid-stimulating hormone (TSH) activity, could be demonstrated; neither was there any response to exogenous human TSH. In the liver, thyroid hormone receptors were found to be primarily of the alpha type. 4. Taken together, these findings suggest that up to 1 year of age, lungfish development is equivalent to amphibian premetamorphosis, which is consistent with neoteny but cannot be taken as evidence for neoteny unless confirmed at later stages of lungfish life history, which are yet to be studied.