Thyroid Epithelial Cell Height Research Articles

Thyroid disruption properties of three indoor dust chemicals tested in Silurana tropicalis tadpoles.

Indoor dust contains a multitude of industrial chemicals, and ingestion of dust is considered an important exposure route to organic contaminants. Some of these contaminants have been shown to interfere with the thyroid system, which may result in significant consequences on public health. The amphibian metamorphosis is a thyroid hormone-dependent process, which can be used as an in vivo model for studies on thyroid hormone-disrupting potency. Three contaminants of indoor dust were tested on metamorphosing Silurana (Xenopus) tropicalis tadpoles. The tested chemicals were Tris (1,3-dichloroisopropyl) phosphate (TDCiPP), tetrabromobisphenol-A (TBBPA) and propylparaben (PrP). Measurements reflecting general growth, development progress and thyroid epithelial cell height were performed on the exposed tadpoles as well as chemical analyses of the exposure water. It was shown that TDCiPP acts as a thyroid hormone-disrupting chemical in metamorphosing tadpoles by causing increased epithelial cell height in thyroid glands after exposure to a nominal concentration of 0.010mg/L and in higher concentrations. TBBPA caused reductions in general growth of tadpoles at the nominal concentration 0.125mg/L, and PrP caused acute toxicity at the nominal concentration 12.5mg/L. However, no evident indications of specific thyroid-disrupting effects caused by TBBPA or PrP were observed.

Abstract 3010: Proteomic analysis of off-target toxicities following treatment with the tyrosine kinase inhibitor sunitinib

Abstract Background: Sunitinib is a multi-targeted agent approved for treatment of a number of cancers. However, since approval, data has continually emerged relating to toxicity profiles including hypertension, hand-foot syndrome and fatigue. Underlying mechanisms are unresolved. It has been hypothesised that the multi-parameter toxicity profile is related to ‘on-target’ kinase inhibition in ‘off-target’ tissues. Methods: To interrogate off-target effects, the Zeptosens Reverse Phase protein Array (RPA) platform was used to assess tissues obtained from mice treated with sunitinib (40 mg/kg) for 4 weeks. Additional tissue was collected for histological analyses and pathophysiologic changes assessed. Results: RPA data analyses on all organs collected (heart, kidney, liver, brain, intestine and skin) revealed the presence of differentially expressed proteins associated with damage and/or stress. Of note, Cyclin D1, MEK and phosphorylated-p21(CIP/WAF1) expression increased by 1.8-fold (p < 0.05), 2.2-fold (p < 0.1) and 1.7-fold (p < 0.1) respectively in the kidneys of sunitinib treated mice. These proteins are associated with kidney damage after chemotherapy, and induction of genes associated with renal immune response, inflammation and apoptosis. Mild proteinuria was observed in sunitinib treated animals, however no gross change in renal glomerular ultrastructure was visible via electron microscopy. Phosphorylated-FGFR1, cleaved Caspase-7, and phosphorylated-cMYC expression decreased by 0.45-fold (p < 0.05), 0.4-fold (p < 0.1) and 0.8-fold (p < 0.1) respectively in the skin of sunitinib treated mice. Down-regulation of these proteins has been associated with a perturbation of cutaneous wound healing (p-FGFR1/cleaved Caspase-7). Mice treated with high dose sunitinib (80 mg/kg) showed overt signs of skin toxicity. Histopathologic studies of the thyroid gland revealed decreased thyroid epithelial cell height (p < 0.05). Nevertheless, serum levels of triiodothyronine and thyroxine remained unchanged. An orthogonal validation study (Western blotting) is ongoing based on gene ontology, pathway analysis and observed fold changes in critical signalling pathway proteins involved in cellular stress. Conclusions: Implementation of a combined histopathologic/ RPA approach may provide a sensitive method to mechanistically elucidate the off-target toxicity sequelae associated with TKIs approved in the oncology setting. Work was supported by an EU funded Industry Academia Pathways and Partnerships Marie Curie Award (AngioTox) Grant Number 251528. RPAs were performed at Bayer Technology Services, Leverkusen, Germany. Citation Format: Alice C. O’Farrell, Adam Lafferty, Ian Miller, Rhys Evans, Maurice Cary, David Murray, Marina Alamanou, Girish Mallya Udupi, Liam Shiels, William M. Gallagher, Annette T. Byrne. Proteomic analysis of off-target toxicities following treatment with the tyrosine kinase inhibitor sunitinib. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3010.

Assessment of the health status of wild fish from the wheatley Harbour area of Concern, Ontario, Canada

The overall health and endocrine function of wild brown bullhead (Ameiurus nebulosus) and goldfish (Carassius auratus) from the Wheatley Harbour Area of Concern (Lake Erie, Ontario, Canada) was assessed using a suite of physiological and biochemical endpoints. Smaller gonads were detected in female brown bullhead and goldfish from Wheatley Harbour compared with Hillman Marsh (Ontario, Canada) reference fish. Female brown bullhead exhibited decreased in vitro synthesis of 17β-estradiol. Female goldfish had decreased plasma vitellogenin concentrations. Plasma testosterone and 11-ketotestosterone were significantly depressed in males of both species. Perturbations in the thyroid status were detected, but varied between sexes and species. Observed differences included lower plasma concentrations of thyroid hormones and/or elevated liver deiodinase activity. Histological evaluation of the thyroid tissue indicated that in the case of female goldfish, those perturbations stimulated the thyroid (as indicated by increased thyroid epithelial cell height) and partially depleted the thyroxine reserves, as indicated by decreased colloid and elevated thyroid activation index. Increased mixed-function oxygenase activity in brown bullhead from Wheatley Harbour was consistent with exposure to planar aromatic contaminants. A principal component analysis of selected variables showed the separation of fish by collection site. The endpoints most strongly associated with the separation were generally those exhibiting significant differences between sites. The results of the present study indicate that the health of fish populations within Wheatley Harbour warrants continued attention.

Thyroid Axis Disruption in Juvenile Brown Trout (Salmo trutta) Exposed to the Flame Retardant β-Tetrabromoethylcyclohexane (β-TBECH) via the Diet

Tetrabromoethylcyclohexane (TBECH) is an additive brominated flame retardant used in domestic and industrial applications. It has been detected in wildlife, and there is early evidence that it is an endocrine disruptor. Whereas other brominated flame retardants with similar physicochemical properties have been shown to disrupt the thyroid axis, no such evaluation has been conducted for TBECH. To elucidate this, juvenile brown trout (Salmo trutta) were fed either a control diet or diets containing low, medium, or high doses of β-TBECH, the isomer most frequently detected in wildlife, for 56 days (uptake phase) followed by a control diet for an additional 77 days (depuration phase). Eight fish per treatment were lethally sampled on uptake days 7, 14, 21, 35, 49, and 56 and on depuration days 7, 21, 35, 49, and 77 to assess fish condition, circulating free and total triiodothyronine and thyroxine, and thyroid epithelial cell height. Although there was no effect on condition factor, there was a significant reduction in total plasma thyroxine in the high dose group and a significant increase in mean thyroid epithelial cell height in the low, medium, and high dose groups during the uptake phase, whereas there were no differences in the depuration phase. These results indicate that β-TBECH may modulate the thyroid axis in fish at environmentally relevant concentrations.

Biotransformation Enzymes and Thyroid Axis Disruption in Juvenile Rainbow Trout (Oncorhynchus mykiss) Exposed to Hexabromocyclododecane Diastereoisomers

Juvenile rainbow trout (Oncorhynchus mykiss) were fed either a reference diet or one of three diets enriched with alpha, beta, or gamma diastereoisomers of hexabromocyclododecane (HBCD, C12H18Br6) for 56 days. This exposure period was followed by 112 days during which all fish were fed the reference diet. Potential effects of HBCD on phase I and II biotransformation enzyme activities and thyroid axis disruption were examined. Disruption of the thyroid axis was most evident in the gamma-HBCD exposed group, as indicated by lower circular FT4 and higher FT3 as well as an increase in thyroid epithelial cell height. However, fish fed the alpha-HBCD enriched diet also exhibited altered glucuronyltransferase activity and thyroid epithelial cell heights and the beta-HBCD group had altered FT4 and FT3 and glucuronyltransferase activity. T4ORD activity was not affected after 14 days, but was significantly lower among all HBCD exposed fish compared to the reference fish after 56 days. Results from these experiments indicate that all isomers have the potential to disrupt thyroid homeostasis.

PCBs can diminish the influence of temperature on thyroid indices in rainbow trout (Oncorhynchus mykiss)

The influence of PCBs on the thyroid status of rainbow trout was assessed at various temperatures to identify if PCB mixtures, as well OH-PCBs produced via biotransformation of parent PCBs, can illicit thyroid effects in fish. Juvenile rainbow trout (Oncorhynchus mykiss) held at 8, 12 or 16°C were exposed to dietary concentrations of an environmentally relevant mixture of PCBs for 30 days followed by a depuration phase. Two additional treatments at 12°C included higher concentrations of PCBs (congeners 77, 126 and 169) known to induce CYP1A in fish (referred to as CYP1A treatment) and PCBs (congeners 87, 99, 101, 153, 180, 183 and 194) known to induce CYP2B in mammals (referred to as CYP2 treatment), to assess the influence of more biologically relevant PCB congeners on thyroid indices in fish. Growth rate and liver somatic index varied with water temperature (p<0.05) but did not differ between PCB exposed and control fish (p>0.05) and mortality was low in all treatments. Changes in some measures of thyroid status were apparent in PCB-exposed fish held in the 12 and 16°C treatments while other measures showed no change in any treatment. The natural inverse relationship between thyroid epithelial cell height (TECH) and temperature, was diminished after 30 days of exposure to PCBs as the epithelial cell height in PCB-exposed fish was significantly augmented in the 12 and 16°C treatments compared to controls at these temperatures (p<0.05). However, after 20 days of depuration, TECH values in the PCB exposed fish returned to control values. The natural linear gradient between T4 outer-ring deiodinase activity (ORD) and temperature was also diminished after 30 days of exposure to PCBs. PCB-exposed fish from the 16°C treatment had significantly lower deiodinase activities (p<0.05) compared to controls at this temperature, but deiodinase activities returned to normal by day 20 of depuration. No differences were observed in T3 inner-ring deiodinase (IRD) activities and plasma concentrations of T3 and T4 in any of the treatments (p>0.05). EROD activity in fish from the CYP1A and CYP2 treatments were elevated compared to control and high dose PCB-exposed treatments (p<0.05), but the inclusion of CYP inducing congeners did not appear to influence any index of thyroid status. Results of this study suggest that exposure of rainbow trout to high concentrations of PCBs and/or OH-PCBs may alter some indices of thyroid status when water temperatures are high, but these changes are within the compensatory scope of the thyroid system based on no change in circulating hormone concentrations, growth rates or mortality.

The impact of the goitrogen 6-propylthiouracil (PTU) on West-African clawed frog ( Xenopus tropicalis) exposed during metamorphosis

This study investigated the suitability of using tadpoles of the West-African clawed frog ( Xenopus tropicalis) for studying adverse effects on the thyroid hormone system after chemical exposure. Tadpoles were exposed to the thyroxine synthesis inhibitor 6-propylthiouracil (PTU) at concentrations between 2–75 mg/L during 14 days. After 5 and 14 days of exposure the developmental stage, hind limb length, body length and weight were measured. Moreover, histological measurements of the thyroid glands were performed after 14 days of exposure. These measurements included maximum thyroid cross-section area, follicular area and epithelial cell height. Tadpoles in the 75 mg/L treatment were less developed and had shorter hind limb length than the control group after 14 days of exposure. No effects were recorded on these parameters at lower PTU concentrations. The histological measurements revealed clear dose–response relationships in both follicular cross-section area and epithelial cell height, with lowest observed effect concentrations (LOECs) recorded at 2 and 5 mg/L, respectively. This study shows that X. tropicalis is a suitable species for detection of thyroid disrupting chemicals. Further, histopathological measurements of thyroid glands are more sensitive parameters compared with apical endpoints when studying adverse effects on thyroid hormone system caused by PTU exposure in X. tropicalis.

Altered thyroid status in lake trout ( Salvelinus namaycush) exposed to co-planar 3,3′,4,4′,5-pentachlorobiphenyl

Recent studies indicate that co-planar 3,3′,4,4′,5-pentachlorobiphenyl (PCB) congeners or their metabolites may disrupt thyroid function in fishes. Although co-planar PCB have been detected at microgram per kilogram levels in fish from contaminated areas, few studies have examined mechanisms whereby, co-planar PCBs may alter thyroid function in fish. We treated immature lake trout by intraperitoneal (i.p.)-injection or dietary gavage with vehicle containing 0, 0.7, 1.2, 25 or 40 μg 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) per kg BW. Blood and tissue samples were collected at various times up to 61 weeks following exposure. The treatments produced sustained dose-dependent elevations of tissue (PCB 126) concentrations. Thyroid epithelial cell height (TECH), plasma thyroxine (T 4) and 3,3′,5-triiodo- l-thyronine (T 3) concentrations, hepatic 5′-monodeiodinase, hepatic glucuronidation of T 4 and T 3, as well as plasma T 4 kinetics and fish growth were analyzed. Exposure to the highest doses of PCB 126 caused increased TECH, plasma T 4 dynamics and T 4-glucuronidation (T 4-G). PCB 126 did not affect 5′-monodeiodinase and T 3-glucuronidation (T 3-G) and there were no effects on fish growth or condition. Because T 3 status and growth were unaffected, the thyroid system was able to compensate for the alterations caused by the PCB 126 exposure. It is clear that concentrations of co-planar PCBs similar to those found in predatory fish from contaminated areas in the Great Lakes are capable of enhancing metabolism of T 4. These changes may be of significance when T 4 requirements are high for other reasons (e.g. periods of rapid growth, warm temperatures, metamorphosis, and parr-smolt transformation).

Temporal changes in plasma thyroid hormone, growth hormone and free fatty acid concentrations, and hepatic 5?-monodeiodinase activity, lipid and protein content during chronic fasting and re-feeding in rainbow trout (Oncorhynchus mykiss)

Temporal changes in growth, plasma thyroid hormone, cortisol, growth hormone (GH) and non-esterified fatty acid (NEFA) concentrations, hepatic T3 content and hepatic 5'-monodeiodinase activity were measured in rainbow trout (Oncorhynchus mykiss) subjected to a sustained fast for up to eight weeks, and during a four-week re-feeding period. The purpose of the study was to examine aspects of the endocrine control of energy partitioning processes characteristic of short-term (acute; fasting) and long-term (chronic; starvation) food-deprivation states in fish, and to explore the role of the thyroid hormones, cortisol and GH in the energy repartitioning that takes place during an acute anabolic (re-feeding) state following chronic food deprivation.Differences in growth rate between fed and fasted groups were evident after two weeks, but significant weight loss by the fasted groups was not evident until between four and six weeks into the fast. Hepatosomatic indices (HSIs) were significantly reduced in the fasted fish within seven days, and as early as two days in one study; recovery of the HSI in fasted fish was evident within three days of re-feeding. Liver protein content (expressed as % wet weight) was consistently depressed in the fasted fish in only one of the three studies. Liver total lipid content (expressed as % wet weight) was depressed in the fasted fish within two days of food deprivation. Because of the rapid and sustained decrease in the HSI of fasted fish, the hepatic total protein and lipid reserves, when considered on a body weight basis, were markedly lowered within the first few days of the fast. Plasma GH concentrations exhibited a bi-modal pattern of change, with a transient fall in levels, followed by a sustained increase in fasted fish. The indicators of interrenal activity were suggestive of a depressed pituitary-interrenal axis in fasted animals; plasma cortisol levels were elevated to levels of fed animals within one day of re-feeding. The indicators of thyroid hormone economy (plasma thyroid hormone levels, liver triiodothyronine content, hepatic 5'-monodeiodinase (MD) activity, thyroid epithelial cell height) were similarly indicative of a depressed pituitary-thyroid axis in fasted animals, with recovery to levels of the fed animals within one week. Despite the compensatory changes in accumulation of reserves (as indicated by a compensatory increase in HSI), there were no apparent compensatory changes in any of the endocrine parameters evident during the re-feeding period.

The influence of the dietary carbohydrate: lipid ratio on the chronic toxicity of sodium pentachlorophenate to rainbow trout (Salmo gairdneri Richardson)

The influence of diets varying in carbohydrate: lipid ratio on the chronic toxicity of waterborne sodium pentachlorophenate (0 or 50 μg NaPCP.l(-1)) to rainbow trout (Salmo gairdneri) was examined over a 12 week period. The three diets used were practical salmonid formulations, equivalent in energy and protein content, with cerelose: fish oil ratios of 18.2∶4.7% (high carbohydrate, HC), 9.3∶9.1% (intermediate, INT), and 0.6∶13.8% (low carbohydrate, LC). With increasing levels of dietary carbohydrate trout exhibited enlarged livers, elevated liver glycogen content, reduced liver protein content, reduced body lipid content, reduced weight gain, and elevated feed: gain ratio. For all diet groups, exposure of trout to NaPCP resulted in reduced liver glycogen content, higher liver protein content, reduced levels of plasma total triiodo-L-thyronine and L-thyroxine, increased thyroid epithelial cell height, and increased feed: gain ratios relative to their respective dietary control group. NaPCP exposure led to nominal reductions in weight gain and body lipid content of fish reared on the HC and INT diets. NaPCP exposed fish on the LC diet gained significantly less weight but had a higher body lipid content than control fish. The increasing NaPCP bioconcentration factor (BCF) associated with increasing lipid content of fish (log BCF=2.75 [log % lipid] +0.30; r=0.95) may explain the differences in response. Correction of bioconcentration data for the lipid content of fish reduced the range in BCF from 5- to 2.8-fold.

Effects of 17β-estradiol and methyl testosterone on the activity of the thyroid gland in rainbow trout, Salmo gairdneri Richardson

Methyl testosterone (MT) and 17β-estradiol (E2), suspended either in sesame oil (and injected on alternate days) or in warm hydrogenated coconut oil (and injected once in the form of an “implant”), were administered intraperitoneally to nonvitellogenic rainbow trout ( Salmo gairdneri Richardson). When given as sesame oil injections E2 significantly reduced plasma triiodo- l-thyronine (T3) levels and thyroid epithelial cell height (TEH), but had no apparent effect on plasma l-thyroxine (T4) levels. When given as a coconut oil “implant” E2 significantly reduced both plasma T3 and T4 levels. E2 also elevated the hepatosomatic index (HSI), plasma Ca 2+, Mg 2+, protein, triglyceride, and alkali-labile phosphoprotein (ALP) and hepatic lipid concentration, decreased hepatic glycogen levels, but was without effect on plasma Na + and glucose levels. MT given via sesame oil injections significantly lowered plasma T3 levels, but was without effect on plasma T4 concentrations or TEH; the T3-lowering effect of MT was not evident when the steroid was given in the form of a coconut oil “implant”. MT also effected a lowering of plasma Mg 2+ and protein and hepatic lipid concentrations, but had no significant effect on HSI, plasma Na +, glucose triglyceride and ALP concentration, or hepatic glycogen levels. MT given as a series of injections lowered plasma Ca 2+ levels, but was without effect when given as an “implant” and had no significant effect on plasma Ca 2+. Intraperitoneal injections of ovine thyrotropin (TSH) (2 μg/g body wt) elicited an increase in both plasma T4 and T3 levels within 24 hr in E2-, MT-, and oil-injected groups. The TSH-stimulated increase in plasma T4 level was significantly less in the E2-treated fish compared with oil- or MT-treated groups. The TSH-stimulated increase in plasma T3 levels in both groups of steroid-treated fish was significantly less than that of the oil-injected controls.

Effect of rearing density on thyroid and interrenal gland activity and plasma and hepatic metabolite levels in rainbow trout, Salmo gairdneri Richardson

There were significant inverse correlations between rearing density of rainbow trout, Salmo gairdneri Richardson, and final body weight, plasma L‐thyroxine (T4), trüodo‐L‐tryronine (T3), cortisol and protein concentrations, plasma T4/T3 ratios and thyroid epithelial cell height. In addition, hepatosomatic indices and plasma free fatty acid concentrations were higher in fish reared at low (134 g 1−1) density compared with groups reared at medium (210g1−1) or high density (299g 1−1), and the post‐feeding (3.5‐4h) elevation in plasma glucose and triglyceride levels evident in trout maintained at low rearing density was not found in those fish reared at higher densities. There were no significant effects of rearing density on hematocrit, carcass composition, hepatic glycogen and lipid levels and interregnal nucleus size.

Ultrastructural changes in the adenohypophysis during the ovarian cycle of the viviparous teleost Poecilia latipinna: II. The thyrotrophic cells and the thyroid gland

Electron microscopical observations were made on the thyrotrophic (TSH) cells during the monthly cycle of oocyte development and pregnancy in female sailfin mollies. Parallel light microscopic studies were made on the thyroid gland. By morphological criteria, TSH secretion and thyroid activity run in parallel, and the findings indicate that TSH secretion and thyroid hormone output are higher during vitellogenic oocyte growth than during earlier oocyte development and during pregnancy. Measurements of TSH cell area and nuclear area and of thyroid epithelial cell height confirm this pattern. The results are discussed in the light of what is known of thyroid hormone involvement in teleostean ovarian physiology.

Some endocrine factors affecting the development of seawater tolerance during the parr-smolt transformation of the amago salmon, Oncorhynchus rhodurus

The development of hypoosmoregulatory abilities assessed by monthly seawater-challenge tests was studied in hatchery-reared amago salmon. At any time from August to May, parr, including precociously mature male and immature small fish, could not regulate serum sodium levels 24 h after transfer to seawater (29‰). The best hypoosmoregulatory performance was obtained from smolts collected in December and January, and this coincided with the peak of smoltification assessed by external appearance. The hypoosmoregulatory capacity of smolts began to decline in February and reached the same levels as parr by May, thus indicating that desmoltification was occurring during the spring. Analysis of weekly plasma samples between 30 August and 14 November demonstrated that the levels of plasma thyroxine of smolts increased significantly just prior to the maximum development of seawater adaptability; parr did not show this increase. The greatest thyroid activity, assessed by changes in thyroid epithelial cell height, was observed in smolts collected in December and January. These results suggest that thyroid hormone is involved in smoltification in the amago salmon. Possible relationships between plasma thyroxine and sex steroid levels in precociously mature male parr and smolts are discussed.

Annual cycles in levels of pituitary and plasma gonadotropin, gonadal steroids, and thyroid activity in the Chinese cobra ( Naja naja)

Adult Chinese cobras, Naja naja, were purchased monthly from a snake dealer in Hong Kong (6–8 animals per month for each sex, total of 290 snakes) and sacrificed after 1 day of acclimation in the laboratory. Pituitary and plasma gonadotropin (Gn), plasma thyroxine (T 4), sex steroids in plasma and testes, and ovarian Gn binding were examined in relation to the annual reproductive cycle. Changes in plasma Gn did not always correspond to pituitary Gn content, and a marked annual cycle in plasma T 4 was evident, despite a lack of change in thyroid weight or epithelial cell height. Although Gn levels were generally elevated during the reproductive season, gonadal activity did not always show the expected relationship to plasma Gn levels. In males, a winter peak in plasma Gn occurred despite low pituitary content; this increase in the plasma coincided with the initiation of testis growth. However, in summer, the testes showed full regression in weight, spermatogenesis, and testosterone (T) secretion, almost 2 months before a decline in plasma Gn was evident. Increased plasma T 4 might be implicated in this apparent dissociation between testis function and circulating Gn levels. Both plasma and testicular T increased only at the time of maximum testicular weight; they did not show the expected increase at the time when spermatogenesis was initiated. In females, plasma Gn showed a bimodal annual cycle but ovarian activity was compressed into a single relatively brief period of about 2 months in spring. A pronounced winter rise in plasma Gn, despite low pituitary Gn levels, was not reflected in detectable ovarian changes. Increases in plasma estradiol (E) and T occurred during the vitellogenic phase; plasma E dropped rapidly after ovulation, but T remained partially elevated until after oviposition. In contrast, plasma progesterone (PRO) did not rise until after ovulation; it then remained fully elevated until after oviposition. Thus, both T and PRO levels along with high Gn binding indicated that the corpora lutea remain functional until oviposition occurs. Steroid levels were reduced to baseline values in animals with atretic follicles. Plasma and pituitary Gn rose during the vitellogenic period and remained elevated until oviposition. Unlike the male, plasma T 4 levels were maximal during the active reproductive period (vitellogenesis and ovulation). The ability of ovarian tissues to bind radiolabeled gonadotropin was lowest in the previtellogenic stages, especially when plasma Gn was highest. Corpora atretica also had significantly reduced binding. We postulate that the ovarian cycle of this snake represents a progressive differentiation in the functional state of the ovary which is induced by relatively constant high levels of a single gonadotropin; thus, functional transitions in ovarian tissue rather than alterations in the nature or concentration of gonadotropins in the circulation are responsible for the changing pattern of ovarian steroid secretion.

Structure of thyroid and adrenal glands in rats fed diets of Great Lakes coho salmon ( Oncorhynchus kisutch)

Feral Great Lakes coho salmon ( Oncorhynchus kisutch) were fed to Sprague-Dawley rats in order to determine the effects of bioaccumulated xenobiotics on mammalian endocrine physiology and assess the risk of human consumption of Great Lakes salmon. Rats fed coho salmon from Lakes Ontario, Erie, and Michigan had enlarged thyroid glands compared with controls fed Pacific Ocean coho or Rat Chow. The thyroid epithelial cell height was significantly increased in the rats fed Lake Ontario coho for 8 weeks, and the cells in this group, and to a lesser extent in the group fed Lake Michigan coho, contained more mitochondria, rough endoplasmic reticulum, Golgi profiles, and colloid-filled vacuoles than those of controls or rats fed Lake Erie coho. Dietary iodide supplementation to rats fed the Lake Ontario coho diet had no effect on either thyroid weight or thyroid histology, suggesting that the goiter was not due to iodide deficiency. The adrenal glands of rats fed coho from Lakes Erie or Michigan were significantly larger ( P < 0.01) than those in all other groups, apparently because of an enlargement of the zonae fasciculata and reticularis. In addition, rats given the Lake Ontario coho diet had markedly dilated sinusoidal spaces in the zonae fasciculata and reticularis of the adrenal cortex and also in the adrenal medulla.

The potential for using the anabolic hormones 17 alpha-methyltestosterone and (or) 3,5,3'-triiodo-L-thyronine in the fresh water rearing of coho salmon (Oncorhynchus kisutch) and the effects on subsequent seawater performance.

Juvenile coho salmon (Oncorhynchus kisutch) held in 11 °C fresh water (FW) were fed Oregon moist pellets supplemented with 3,5,3′-triiodo-L-thyronine at 4 ppm (T34) or 20 ppm(T320) and (or) 17α-methyltestosterone at 0.2 ppm (MT0.2) or 1 ppm (MT1) until early or normal seawater (SW) transfer.During FW residency all hormonal treatments improved growth, appetite, and food utilization. In February, fish fed T320 singly or with MT had increased degranulation of somatotrop cytoplasm. Thyroid epithelial cell height of fish fed T34 or T320 was either suppressed or enhanced. MT1 singly or combined with T3 induced androgenic side effects in males. Proximate body composition was affected only by MT. T320 induced morphological anomalies and treatment was discontinued. In May, thyroid activity and number of putative gonadotrops of fish fed MT1 were increased. Androgenic effects of all groups given MT1 were greater in May than in February.After SW transfer in February growth, appetite, and food utilization were depressed but fish fed T34 performed better than controls. Performance of all groups improved after May but, in general, mortality increased slightly. After transfer in May, T3-fed fish had increased growth in length.It is concluded that MT and T3 effectively enhance growth in FW but only T3 facilitates SW transfer.

Seasonal changes in thyroid activity in the lesser snow goose (Anser caerulescens caerulescens) including reference to embryonic thyroid activity.

Plasma thyroxine (T4) levels in adult lesser snow geese (Anser caerulescens caerulescens) increased concomitantly with gonadal recrudescence and remained elevated until shortly before moult. This pattern of declining plasma T4 concentrations preceding moult was evident in gosling, yearling, and adult birds. Plasma triiodothyronine (T3) concentrations did not change significantly throughout the year. There was no apparent correlation between plasma thyroid hormone levels and thyroid weight or thyroid epithelial cell height. Plasma levels of both T3 and T4 increased in goslings shortly before hatch and on day 20 of incubation reached levels (0.58 ± 0.36 and 19.5 ± 2.5 ng∙mL−1, respectively) similar to those found in the plasma of newly hatched birds (0.76 ± 0.24 and 36.0 ± 6.5, respectively).

Thyrotropin from amphibian ( Rana catesbeiana) pituitaries and evidence for heterothyrotropic activity of bullfrog luteinizing hormone in reptiles

Evidence is presented for the isolation of a third glycoprotein hormone from the pituitary of the bullfrog ( Rana catesbeiana) identified as thyrotropin (TSH) on the basis of its ability to stimulate various aspects of thyroid function in the homologous species (e.g., thyroxin release, thyroid epithelial cell height, and metamorphic stimulation). In contrast, bullfrog luteinizing hormone (LH) and follicle-stimulating hormone (FSH) had relatively little effect on the bullfrog thyroid. This bullfrog TSH was also compared with the two bullfrog gonadotropins in several reptilian thyrotropin bioassays (e.g., stimulation of thyroxine release, radioiodine uptake, and thyroid epithelial cell height in a turtle, Pseudemys, and radioiodine uptake in a lizard, Anolis). In these heterologous species, bullfrog LH was the most potent thyrotropic factor of the three frog hormones; whereas, bullfrog TSH and FSH had little activity. Bullfrog LH, therefore, functions as a “heterothyrotropin” in a heterologous species. These results provide evidence that the thyrotropin-receptor complex in the Reptilia has undergone extensive independent evolution such that its thyroid receptor preferentially reponds to the LH rather than to the TSH from another class.

Dehydroepiandrosterone-induced thyrotrophin release during heat stress in rats.

Six groups each of 12 male albino rats were reared from day 21 of life at temperatures of 23, 34 or 37 degrees C. While the rats survived for unlimited periods at 23 and 34 degrees C, the animals reared at 37 degrees C succumbed within 5 days to heat stress. The latter group, when injected s.c. or i.p. with 50 mg dehydroepiandrosterone (DHA)/kg/day were no longer affected by the heat. During this treatment thyroid epithelial cell height doubled, colloid decreased by 20%, connective tissue did not change, the basic metabolic rate decreased by 10% and rectal temperatures of the treated rats increased with the ambient temperatures. Body weight increased only slightly, pituitary TSH decreased by 25%, serum TSH increased by over 50%, thyroxine and 125I uptake increased by 200%. The survival of the DHA-treated rats was apparently secured by blocking the hypothalamic thermoreceptors.