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Biomedical subjects

F M McNabb

Publications and source records attributed to F M McNabb.

At least 19 recordsLinked to original sources

Developmental effects of testosterone on behavior in male and female green anoles (Anolis carolinensis).

This study addressed the role of testosterone (T) in the development of sexually dimorphic behavior in the green anole lizard, Anolis carolinensis. We documented the pattern of endogenous T concentrations during ontogeny and we determined the behavioral effects of experimentally elevated T in juvenile males and females. T concentrations were measured in the plasma of hatchlings from eggs incubated in the laboratory, in juveniles of all sizes sampled in the field, and in the yolks of freshly laid eggs in the laboratory and were compared to plasma T in adult females (measured in this study) and adult males. There were no sex differences in plasma T in hatchling and small juvenile (<26-mm snout-vent length, SVL; <14 days old) males and females, concentrations of which in both sexes tended to decline over the 14-day posthatching period. Plasma T sharply increased in juvenile males, but not females, after approximately 14 days posthatching (>25-mm SVL), and it became significantly higher after approximately 38 days posthatching (>30-mm SVL). Plasma T for juvenile males was within the range detected in breeding adult females, but it was 20- to 45-fold lower than that of adult males, breeding or postbreeding. All eggs contained detectable yolk T, but eggs that gave rise to males contained nearly twice as much yolk T as those that gave rise to females. We do not know whether this yolk T comes from the mother, embryo, or both. In behavior trials conducted in the laboratory, juveniles (36- to 42-mm SVL) with T implants, regardless of whether they were male or female, had increased activity levels compared to juveniles with blank implants, due to increased rates of nearly every behavior monitored. These results are discussed in the context of the organization-activation theory of sexual differentiation and the particular life history of A. carolinensis.

Aging↗

Patterns of testosterone and prolactin concentrations and reproductive behavior of helpers and breeders in the cooperatively breeding red-cockaded woodpecker (Picoides borealis).

We examined the proximate causes of delayed breeding and alloparental behavior in the cooperatively breeding red-cockaded woodpecker by measuring plasma concentrations of testosterone (T) and prolactin (PRL) in female breeders, male breeders, and male helpers during different stages of the reproductive cycle. Male breeders and helpers have low T during the prebreeding period, highest T during copulation, and low concentrations of T during the egg-laying/incubation and nestling provisioning stages. Helpers appear physiologically capable of reproducing; their T concentrations equal that of male breeders. Helpers unrelated to the breeding female have higher T than helpers sharing a territory with their mother. Sexual inactivity by male helpers might be explained by behavioral suppression resulting from interactions of male helpers with the breeding pair that somehow differ in accordance with the helper's relatedness to the breeding female (e.g., female breeders are generally unreceptive to courtship from male helpers and least receptive to related helpers). Female breeder, male breeder, and male helper PRL levels did not differ and increased from the prebreeding stage through the copulation and egg-laying/incubation stages. During the nestling provisioning stage, male breeder and helper PRL declined, while female PRL continued to increase. Based on these results, we conclude that the physiological bases of alloparental behavior have not diverged from those that mediate parental behavior in this species.

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Thyroid development in relation to the development of endothermy in the red-winged blackbird (Agelaius phoeniceus).

We investigated the development of thyroid function during the transition to endothermy in red-winged blackbirds (Agelaius phoeniceus). Thermoregulatory capabilities of blackbirds improve markedly over their relatively short nestling period (10-12 days), with the most striking improvements occurring between days 6 and 8. We hypothesized that the development of endothermy in these birds is dependent in part on the development of thyroid function. We assessed thyroid development by measuring changes in thyroid gland histology and plasma concentrations of thyroxine (T4) and triiodothyronine (T3) during the nestling period. To gain insight into the role of thyroid maturation in the context of thermoregulation, we compared plasma thyroid hormone profiles in nestlings exposed to cold temperatures to those maintained at thermoneutral temperatures. The overall size of the thyroid (as cross-sectional area) increased during nestling development, with the fastest growth occurring just before the development of endothermy. By day 8, it reached the size typical of that in adults. Follicular cell height of the thyroid glands increased in nestlings up to day 6 and then decreased for the rest of the nestling period. The mean area of individual follicles increased up to day 8 of nestling life and then decreased. Individual nestlings were capable of strong endothermic responses at 7 to 8 days of age and had significantly decreased plasma T4 concentrations following cold exposure, suggesting increased T4 to T3 deiodination to maintain the plasma concentrations of the more metabolically active T3. The patterns of plasma T4 and T3 during nestling development were consistent with those of nestlings of other altricial species of birds that have been studied. Overall, the patterns of thyroid development observed were consistent with the hypothesis that the functional development of the thyroid is critical to the development of endothermic capabilities and that thyroid hormones play a role in endothermic responses to cold temperatures.

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Maternal thyroid hormones in Japanese quail eggs and their influence on embryonic development.

We addressed the relationship between the thyroid status of hens and the thyroid hormone content of their eggs, as well as the influences of egg hormones on embryonic development. Methods for measuring thyroid hormones in egg yolk were verified by demonstrating consistency in the recovery of yolk thyroid hormones following a methanol/chloroform extraction and in the measurement of thyroid hormones by RIA for a range of hormone concentrations in yolk extracts. Untreated hens produced eggs with yolk thyroxine (T4) concentrations that were low relative to plasma T4, but yolk triiodothyronine (T3) concentrations comparable to those of plasma. Hens dosed twice daily with T4 (1 or 3x the daily thyroid secretion rate, TSR, of T4 per dose) had significantly higher plasma and egg yolk T4 concentrations than did control hens dosed with saline. In general, the T4 concentration of egg yolk varied with the thyroid status of the hen. When the relationship between each hen's plasma T4 and the yolk T4 concentration of her eggs was examined, hens appeared to regulate T4 deposition into yolk at "levels" characteristic of the "levels" of thyroid status produced by the different doses of T4. Embryonic pelvic cartilage, a thyroid hormone-responsive tissue, showed enhanced growth and differentiation in embryos from eggs of hens given the highest dose of T4. Specifically, alkaline phosphatase activity (a marker of differentiation) and pelvic cartilage wet and dry weights were significantly greater in embryos from high T4 eggs (hens on the 3x TSR dose) than those in controls. However, embryos from high T4 eggs did not differ in general body growth (body weight, length, and general morphology) or hatchability compared to controls. In a single T3 experiment, hens were dosed twice daily with 1 microg T3. The embryos from eggs of these hens had accelerated differentiation/maturation of pelvic cartilages (sampled at Day 12) compared to those from control eggs; body growth did not differ from that of controls.

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Comparison of the ontogenesis of thyroid hormones, growth hormone, and insulin-like growth factor-I in ad libitum and food-restricted (altricial) European starlings and (precocial) Japanese quail.

In this study, we compare the ontogenic patterns for thyroid hormones, growth hormone (GH), and insulin-like growth factor-I (IGF-I) in altricial European starlings and precocial Japanese quail and examine the effects of feed restriction on these species. The most marked difference in development between the altricial and precocial birds was with respect to plasma thyroid hormone patterns. In the starling, circulating concentrations of triiodothyronine (T3) and thyroxine (T4) were very low in embryos, then increased progressively after hatching to peak at 10-11 days of age. In contrast, in quail, in which other studies have shown that most thyroid maturation occurs during the embryonic and peri-hatch periods, the circulating concentrations of T3 and T4 showed little posthatch ontogenic change. Plasma concentrations of both GH and IGF-I showed similar patterns in both species with a posthatch rise (peak at 3 days in starlings and 8 days in quail), followed by a decline. Food restriction to maintain body weight resulted in decreased plasma concentrations of T3 and IGF-I in both species. After return to ad libitum feeding, plasma T3 and IGF-I increased in both early and late restricted starlings and in late restricted quail. Although both species responded to food restriction with similar patterns of endocrine change, age-related differences in the magnitude of hormonal responses were observed.

Aging↗

Thyroid hormones, their activation, degradation and effects on metabolism.

The control of both metabolism and developmental events by thyroid hormones involves a variety of metabolic modifier effects. These actions of thyroid hormones are mediated by nuclear thyroid hormone receptors that have their highest affinity for triiodothyronine (T3). Thyroid hormone deiodinations can have activating or inactivating effects, with the production of T3 (the most active form) and its degradation being of key importance. At the organismic level, the development of thermogenic metabolic responses necessary for homeothermy in birds is correlated with the pattern of thyroid development and the extrathyroidal deiodinations of thyroid hormones. At the cellular level, deiodination effects on cellular T3 availability can protect T3 supply for critical developmental processes (e.g., in brain) or potentially play a role in the differentiation and maturation of various hormone-responsive tissues. Thyroid hormones, both alone and through interactions with other hormones and growth factors, also can influence intermediary metabolic responses that, in turn, play roles in growth and development.

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Intestinal 5'deiodinase activity of developing and adult chickens selected for high and low body weight.

Intestinal 5'deiodinase activity (5'D) in adults from lines of chickens selected for high (HW) and low (LW) juvenile body weight was studied in vitro using reverse T3 substrate. This avian intestinal 5'D activity is similar in its biochemical characteristics to the hepatic 5'D activity of mammals and birds. Adult 5'D activity was higher in line HW than LW; a pattern opposite to that prior to hatching. Previous studies have shown that thyroid hormones are important in triggering differentiation of the intestine during the latter part of embryonic life. Our studies indicate that the intestinal tissue is capable of producing T3 that may be important in stimulating differentiation of the intestine itself, in preparation for posthatching food assimilation. The intestines of LW embryos, which hatch earlier than HW embryos, show both more rapid maturation, as indicated by intestinal alkaline phosphatase activity (a marker of differentiation), and higher 5'D activity. Increases in intestinal 5'D in the HW line at hatch may be important in the differential intestinal growth that leads to higher relative intestinal weights in HW than LW chicks after hatch. The magnitude of 5'D activity and the relative size of the intestine suggest that this organ could be an important contributor to plasma T3.

Alkaline Phosphatase↗

Perinatal thyroid hormones and hepatic 5'deiodinase in relation to hatching time in weight-selected lines of chickens.

Plasma thyroid hormone concentrations, liver weight, body weight, and hepatic capability for triiodothyronine (T3) production were measured at 8-h intervals on Days 19 through 21 in embryos and chicks from lines selected for high (HW) and low (LW) body weight at 8 wk of age. Embryos were categorized as not having entered the perinatal period (nonpipped, NP) or as being in one of three perinatal stages: embryos that had pipped into the air cell (AC), embryos pipped through the shell (TS), and chicks within 24 h of hatching (H). Both plasma thyroxine (T4) and T3 peaked at the TS stage in embryos of both lines. Embryos had higher concentrations of both hormones and hatched earlier in the LW than in the HW line. This association and evidence from other studies is suggestive that T3 may be playing a role in line differences in hatching time. Hepatic 5'deiodinase (5'D) activity was higher in LW than HW embryos and chicks at the AC, TS, and H stages although the opposite had been the case prior to the perinatal period (NP stage). Hepatic 5'D increased at each stage from AC to TS to H. When the patterns of liver growth and body weight were considered, this pattern and the differences between the lines were exaggerated further. Comparison of the plasma and 5'D patterns during the perinatal period suggests that substrate (T4) supply may be more important than 5'D capability of the liver in determining the pattern of T3 supply during some of these stages.

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Hepatic 5'-deiodinase activity of Japanese quail using reverse-T3 as substrate: assay validation, characterization, and developmental studies.

Using rT3 as substrate, an in vitro 5'D assay was validated for use with liver tissue from adult Japanese quail, by defining conditions under which activity is proportional to enzyme (protein) concentration and is linear with incubation time. Activity was measured as the release of 125I from labeled rT3. Using validated assay conditions we found the following 5'D characteristics: maximal activity from 10 to 50 mM dithiothreitol (cofactor), an apparent Km of 0.52 microM rT3, pH optimum of 7.6-8.5, complete inhibition by 1 mM propylthiouracil and by 1.0 mM iopanoic acid, and substrate "preference" of rT3 greater than T4 greater than T3. Based on these characterizations the quail hepatic 5'D activity is like the Type I 5'D activity found in mammalian liver and kidney and embryonic chicken liver. To determine how previous unvalidated assays, that used high tissue and relatively low substrate (T4) concentrations, influenced 5'D studies we reevaluated 5'D development using an assay validated for each developmental stage with rT3 as substrate. We found extreme quantitative differences in the activities measured and in the proportional relationships between stages, and only limited qualitative similarity in the pattern of 5'D development when unvalidated T4 assay results were compared with validated rT3 assay results. Our data in this paper show good correspondence between whole liver 5'D activity per unit body weight and plasma T3/T4 ratios for the developmental stages sampled.

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Assay validation and characterization of hepatic 5'-deiodinase activity in ring doves using reverse-T3 as substrate.

Adult ring dove hepatic 5'-deiodinase (5'D) activity was studied in vitro using reverse T3 (rT3) as substrate. A previous study of ring dove hepatic deiodinase in our laboratory did not include characterization studies and was unsuccessful in relating the pattern of 5'D development to that of plasma T3. In the present study we established valid assay conditions and characterized the hepatic 5'D in doves to provide a comparison with other avian species and 5'D activity is proportional to enzyme concentration (as postmitochondrial fraction (PMF) protein) over the range measured (0-0.163 mg PMF protein/ml, representing 0-2.19 mg original tissue/ml). Activity was linear with time from 5 to 30 min of incubation at 0.163 mg PMF protein/ml. Our 5'D assays used 20 mM DTT; activity was maximal from 5 to 30 mM DTT. Using the validated conditions the following characteristics were found: the apparent Km was 0.44 microM rT3, Vmax was 255 pM rT3 degraded/min-mg PMF protein, and activity was completely inhibited by 1 mM PTU. Activity was maximal at pH 8.04 and at 37.5 degrees (although this did not differ from activity at 41.5 degrees, the body temperature of doves). In summary, this study demonstrates conditions that measure 5'D at initial velocities in dove liver and demonstrates that the hepatic 5'D enzyme in ring doves is similar to the deiodinase activity in liver of galliform birds and mammals.

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Hepatic 5'-deiodination in chickens from lines selected for high and low body weight and their F1 cross.

1. Assay conditions for measuring hepatic 5'-deiodinase (5'D) activity at initial velocity, using reverse T3 as substrate, have been validated for adult chicken liver. 2. The characteristics of hepatic 5'D activity in adult chickens from lines selected for high (HW) and low (LW) juvenile body weight are similar to those in mammals and in the other birds that have been investigated. 3. Chickens from the HW line have significantly higher specific activity of hepatic 5'D, and thus potentially higher T3 production, than those from either the LW line or the F1 cross (HL) between the HW and LW lines.

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The effects of different iodide availabilities on thyroid function during development in Japanese quail.

Japanese quail (Coturnix japonica) were used to study the effects of different egg iodide (I) availabilities on thyroid function during development. Low (less than 50 micrograms 1/kg feed in the maternal diet) and high (1200 micrograms 1/kg feed) I availability were compared to control levels (800 micrograms 1/kg feed), a standard supplementation for game bird feed. We measured thyroid gland content of I, triiodothyronine (T3) and thyroxine (T4), plasma concentrations of T3 and T4, hepatic 5' monodeiodinase (5'-D) activity, and the response of the thyroid gland to thyrotrophin (TSH) stimulation. Embryos, on day 14 of the 16.5-17 day incubation period, and 1-day chicks were used for most studies but thyroid gland hormone content and plasma hormone concentrations were determined for more stages. With high I, thyroidal I content was elevated but thyroidal T4 and T3 were not different from controls. Plasma T3 and T4, the thyroid gland response to TSH stimulation, and hepatic 5'-D activity did not differ between control and high I. Reduced body weight occurred with high I. In general, thyroid gland weight was not altered, but some high I birds exhibited thyroid hypertrophy and altered thyroid gland function. With low I availability, thyroid gland contents of I and T4 were reduced but thyroidal T3 content was maintained. The thyroid gland response to TSH stimulation, plasma thyroid hormone concentrations, and the developmental patterns of plasma thyroid hormones, hepatic 5'-D activity, body weight and thyroid weight were not different between control and low I groups. Developing Japanese quail exhibit excellent ability to adjust thyroid function over a wide range of I availabilities. Regulation appears to occur at the level of thyroid hormone synthesis in the thyroid gland, which allows most aspects of thyroid dynamics to remain unchanged in the maintenance of circulating thyroid hormone concentrations.

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Thyroid function in embryonic and early posthatch chickens and quail.

Technological advances, especially radioimmunoassays, have led to good descriptive information about the timing and pattern of development of the thyroid gland (TG) and circulating thyroid hormone (TH). Immunocytochemical studies in combination with more traditional techniques such as gland ablation and hormone replacement have revealed the time of appearance of each hormone in the axis, the relative amounts of hormone present in each gland at different developmental stages, and a general picture of the pattern of maturation of the hypothalamic-pituitary-thyroid axis. Studies of the pituitary control of the TG remain limited by the lack of adequately specific techniques for measuring avian thyroid-stimulating hormone. Our understanding of peripheral TH dynamics is progressing as a result of iodothyronine deiodinase assays but full understanding will require more elaborate studies that adequately characterize the enzyme system(s) in each case. Molecular techniques have made powerful strides in identifying the gene responsible for producing a protein that appears to be the triiodothyronine receptor. Receptor assays have revealed the pattern of changes in receptor-binding capacities during development but have not yet revealed how binding of hormone to the receptor triggers cellular activity. Molecular genetic techniques are being used to reveal the mechanisms whereby some examples of developmental events (e.g., malic enzyme synthesis) are induced by TH. Although it is not yet possible to assess the value of molecular studies in this area for developing practical applications, these techniques are revealing the fundamental biological roles of TH in growth and development.

Animals↗

Thyroid hormones and growth patterns of embryonic and posthatch chickens from lines selected for high and low juvenile body weight.

Lines of chickens divergently selected for high (HW) or low (LW) 56-day posthatch body weight were evaluated for growth, development of small intestine, liver and pectoral muscle, and plasma T3 and T4 concentrations. Measurements were taken at 11,17, and 20 days of incubation and 5, 12, 20, 31, and 61 days posthatch. HW chicks and their organs were consistently larger than LW chicks and their organs from day 17 of incubation onward, and followed growth patterns characteristic of these lines. Significant line by age interactions indicated that chickens divergently selected for juvenile body weight had different temporal patterns for plasma T3 and for T4 from 11 days of incubation to 61 days posthatch. There were no differences between males and females within each line for either T3 or T4. There were no simple relationships between the patterns of plasma concentrations of either T3 or T4 and the pattern of growth of the body or the organs studied.

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Development of thyroid function and its pituitary control in embryonic and hatchling precocial Japanese quail and altricial Ring doves.

We compared the developmental pattern of thyroid function and its pituitary control in precocial Japanese quail and altricial Ring doves. We measured thyroid hormone (TH) content of thyroid glands (TG), TH concentrations in the serum, relative pituitary gland thyrotropin (PG-TSH) content, and the ability of the TG to respond to exogenous TSH as indicated by increases in TG-3',5'-monophosphate (cAMP) content or in serum TH concentrations. In embryonic quail there is considerable maturation of thyroid function prior to hatching. TG-TH content is low but detectable in Day 8 embryos; TG-TH content increases 300x between Day 8 and hatching (16.5-day incubation). Pituitary TSH is detectable by bioassay in quail on embryonic Day 8, with higher levels found closer to hatching. The TG of 8-day embryos responds to TSH injection by increased TG-cAMP content but the serum TH response to TSH does not appear until Day 9. Serum TH concentrations suggest that the TG is under pituitary control during the latter part of incubation. In doves most of the development of thyroid function and the maturation of its pituitary control occur after hatching and thus thyroid functional development is much later in doves than in quail. TG-TH content is extremely low in embryos and nestlings up to 3 days after hatching, increases slowly in nestlings up to Day 10, then increases sharply. Serum TH content is very low in embryos and rises steadily in nestlings to plateau after about Day 8. Pituitary TSH content, estimated by a quail bioassay, is undetectable in embryos and nestlings until Day 4 but increases thereafter. The TG does not respond (based on serum TH concentration) to TSH injection through the day of hatching (Day 16; mean incubation period of 16.5 days), but an increase in serum TH occurs in Day 2 nestlings in response to TSH injection. The magnitude of this response continues to increase during the first week after hatching.

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Thiouracil and antibody titers of chickens from lines divergently selected for antibody response to sheep erythrocytes.

Chickens from lines selected for high (HA) and low (LA) antibody response to sheep red blood cells (SRBC) were fed ad libitum either a diet containing 0 (control) or .1% thiouracil (TF) throughout two trials. Chicks were injected intravenously with .1 ml of .25% SRBC at 37 days of age in Trial 1, and a booster of the same dosage was given to half of these chicks at 61 days of age. Antibody titers were measured 5 and 3 days after primary and secondary inoculations. In Trial 2, primary inoculations of SRBC were given at 21 and 38 days of age, and chicks were bled 3, 5, 7 and 10 days after inoculation. TF chicks had lower body weights and higher feed efficiencies than controls. Plasma thyroxine (T4) concentrations were similar for both lines, but line by diet interactions were present for plasma triiodothyronine (T3) and T3/T4 ratios. When fed the control diet, T3 concentrations and T3/T4 ratios were higher for line HA than line LA, but the pattern was reversed when thiouracil was fed. Antibody titers to SRBC in both trials were higher for HA than LA chicks, but were similar for TF and control chicks. Persistence of elevated titers appeared to be greater in TF than control chicks. There were no differences between TF and control chicks for heterohphil/lymphocyte ratios.

Animals↗

Comparative thyroid function in adult Japanese quail and ring doves: influence of dietary iodine availability.

Thyroid function was studied in Japanese quail, Coturnix japonica, and Ring doves, Streptopelia risoria, when both were fed the same dietary iodine (I; 930 micrograms I/kg). We also compared thyroid function in groups of doves receiving low I (less than 100 micrograms I/kg) or moderate I (930 micrograms I/kg). We measured thyroid gland (TG) weight, TG stable I content, TG 125I uptake, and 125I labeling of thyroid hormones. Triiodothyronine (T3) and thyroxine (T4) concentrations in TGs and serum were also determined. Our results indicate that doves and quail receiving the same dietary I show similar serum T3 (the presumed metabolically active hormone) and TG functional state but that there are some differences between the species in the way in which this functional state is achieved. We also assessed the effects of differences in I availability on thyroid function in doves. With low dietary I doves show decreases in some measures of thyroid function (reduced serum T4 and TG-hormone stores) compared to doves with moderate I but maintain a comparable level of serum T3. This regulation of T3 appears to be independent of serum T4 or TG-hormone stores.

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