Peripheral ghrelin reduces food intake and respiratory quotient in chicken.

Ghrelin injection, either centrally or peripherally strongly stimulates feeding in human and rodents. In contrast, centrally injected ghrelin inhibits food intake in neonatal chickens. No information is available about the mechanism and its relationship with energy homeostasis in chicken. Since ghrelin is predominantly produced in the stomach, we investigated the effect of peripherally injected ghrelin (1 nmol/100g body weight) on food intake and energy expenditure as measured in respiratory cells by indirect calorimetry for 24h in one-week-old chickens. Plasma glucose, triglycerides, free fatty acids, total protein and T(3) were measured in a separate experiment until 60 min after injection. Food intake decreased until at least 1h after intravenous ghrelin administration. The respiratory quotient (RQ) in ghrelin-injected chickens was reduced until 14 h after administration whereas plasma glucose and triglycerides concentrations were not altered. Free fatty acids and total protein levels also remained unchanged. Ghrelin did not influence heat production and this was supported by the absence of changes in plasma T(3) levels when compared to the control values. In conclusion, peripheral ghrelin reduces food intake as well as RQ and might influence the type of substrate (macronutrient) that is used as metabolic fuel.

The release of growth hormone (GH): relation to the thyrotropic- and corticotropic axis in the chicken.

In the chicken and other avian species, the secretion of GH is under a dual stimulatory and inhibitory control of hypothalamic hypophysiotropic factors. Additionally, the thyrotropin-releasing hormone (TRH), contrary to the mammalian situation, is also somatotropic and equally important in releasing GH in chick embryos and juvenile chicks compared to the (mammalian) growth hormone-releasing hormone (GHRH) itself. Consequently, the negative feedback loop for GH release not only involves the insulin-like growth factor IGF-I but also thyroid hormones. In adult chickens, TRH does no longer have a clear thyrotropic activity, whereas its somatotropic activity depends on the feeding status of the animal. In addition, as in mammals, the secretion of GH and glucocorticoids is stimulated by ghrelin, a novel peptide predominantly synthesized in the gastrointestinal tract. Two chicken isoforms of the ghrelin receptor have been identified, both of which are highly expressed in the hypothalamus and pituitary, suggesting that a stimulatory effect may be directed at these levels. GH and glucocorticoids control the peripheral thyroid hormone function by down-regulating the hepatic type III deiodinating enzyme (D3) in embryos (GH and glucocorticoids) and in juvenile and adult chickens (GH). Moreover, glucocorticoids help to regulate T3-homeostasis in the brain during embryogenesis by stimulating the type II deiodinase (D2) expression. This way not only a multifactorial release mechanism exists for GH but also a functional entanglement of activities between the somatotropic-, thyrotropic- and corticotropic axis.

Iodothyronine deiodinases and the control of plasma and tissue thyroid hormone levels in hyperthyroid tilapia (Oreochromis niloticus).

Thyroid status is one of the most potent regulators of peripheral thyroid hormone metabolism in vertebrates. Despite this, the few papers that have been published concerning the role of thyroid hormones in the regulation of thyroid function in fish often offer conflicting data. We therefore set out to investigate the effects of tetraiodothyronine (thyroxine) (T4) or tri-iodothyronine (T3) supplementation (48 p.p.m.) via the food on plasma and tissue thyroid hormone levels as well as iodothyronine deiodinase (D) activities in the Nile tilapia (Oreochromis niloticus). T4 supplementation did not induce a hyperthyroid state and subsequently had no effects on the thyroid hormone parameters measured, with the liver as the sole notable exception. In T4-fed tilapias, the hepatic T4 levels increased substantially, and this was accompanied by an increase in in vitro type I deiodinase (D1) activity. Although the lack of effect of T4 supplementation could be partially explained by an inefficient uptake of T4 from the gut, our current data suggest that also the increased conversion of T4 into reverse (r)T3 by the D1 present in the liver plays an important role in this respect. In addition, T3 supplementation increased plasma T3 and decreased plasma T4 concentrations. T3 levels were also increased in the liver, brain, kidney, gill and white muscle, but without affecting local T4 concentrations. However, this increase in T3 availability remained without effect on D1 activity in liver and kidney. This observation, together with the 6-n-propylthiouracyl (PTU) insensitivity of the D1 enzyme in fish, sets the D1 in teleost fish clearly apart from its mammalian and avian counterparts. The changes in hepatic deiodinases confirm the role of the liver as an important T3-regulating tissue. However, the very short plasma half-life of exogenously administered T3 implies the existence of an efficient T3 clearing/degradation mechanism other than deiodination.

Regulation of thyroid hormone availability in liver and brain by glucocorticoids.

Glucocorticoids as well as thyroid hormones are essential for normal brain development. Exogenous glucocorticoids stimulate 3,3',5-triiodothyronine (T(3)) availability in circulation of birds and similar effects have been observed in sheep. Chicken data indicate that glucocorticoid administration also stimulates thyroid hormone metabolism in brain but the effects on local thyroid hormone concentrations are not known. Therefore, the current study: (1) determined local thyroid hormone availability in separate brain areas of 18-day-old embryonic chickens (E18) after injection of dexamethasone (DEX), and (2) investigated the impact on the thyroid hormone metabolic pathways in these brain parts and compared the results with the hepatic situation. For this, E18 chicken embryos were treated with a single intravenous dose of DEX (25 microg). Despite the decreased 3,5,3',5-tetraiodothyronine (T(4)) availability in the liver of the DEX treated embryos, the T(3) content was strongly increased, parallel to the plasma T(3) surge. This T(3) surge was primarily related to a fall in hepatic T(3) breakdown through a downregulation of the type III deiodinase (D3). The sulfation pathway in liver seems not to be affected by DEX. In all brain parts, DEX affects the T(3) production capacity by upregulation of the type II deiodinase (D2). This enables the brain to compensate for the decrease in T(4) availability, although the T(3) concentrations are not consistently increased like in plasma and liver. This observation points to the existence of a fine-tuning mechanism in brain that enables the brain to keep the T(3) concentrations within narrow limits.

Dynamics and regulation of intracellular thyroid hormone concentrations in embryonic chicken liver, kidney, brain, and blood.

The intracellular thyroid hormone (TH) availability is influenced by different metabolic pathways. We investigated the relationship between tissue and plasma TH levels as well as the correlation with changes of deiodination and sulfation during chicken embryonic development. From day 14 until day 19, T3 remains unchanged in liver and kidney in spite of increasing plasma T4 and T3 levels and a slightly increased T4 availability in these tissues. During this period, the T3 breakdown capacity by type III deiodinase (D3) is high in liver but low in kidney. The TH inactivation capacity of type I deiodinase (D1), with production of inactive rT3 instead of T3, in kidney seems to be potentiated by the sulfation pathway. A sharp rise in T3 and T4 is detected in all tissues examined when the embryo switches to lung respiration. The same day, T4 content in liver is sharply enhanced and sulfation activity is decreased. So, T4 availability in liver is increased while a declined D3 activity allows for the accumulation of hepatic T3. The increase in renal T3 and T4 are more closely related to plasma TH profiles and a lack of correlation with the changes in renal D1 and D3 activity suggests that T4 and T3 content in this organ is strongly dependent on direct uptake from the blood. Despite much lower T4 levels, T3 levels in brain are in the same range as in liver and kidney and intracellular T3 even exceeds the T4 levels towards the end of development. The rise in TH content coincides with a drop in D3 activity, low sulfation activity and an increased T3 production capacity via type II deiodinase (D2). In conclusion, the current study describes the dynamics of intracellular TH concentrations in liver, kidney, and brain during chicken development and investigates their relationship with circulating TH levels and changes of deiodinases and sulfotransferases. The clear differences in intracellular TH profiles among the different tissues demonstrate that circulating levels are not necessarily representative for the local TH changes. Some of the changes in intracellular TH availability can be linked to changes in local deiodination and sulfation capacities, but the importance of these enzyme systems in relation to other factors, such as hormone uptake, differs between liver, kidney, and brain.

Distribution and regulation of chicken growth hormone secretagogue receptor isoforms.

Chicken ghrelin has recently been isolated as a hormone which stimulates growth hormone and corticosterone secretion in chicken. Ghrelin mediates these actions in mammals by binding to the growth hormone secretagogue receptor (GHS-R). In this study, we describe the partial cloning of two chicken GHS-R (cGHS-R) isoforms: cGHS-R1a and cGHS-R1c. cGHS-R1a and cGHS-R1c cDNA show, respectively, 81 and 78% homology with the corresponding parts of the human GHS-R1a cDNA. In contrast to the human GHS-R1b isoform, which is truncated after transmembrane domain 5 (TM-5), the chicken GHS-R1c isoform lacks 16 amino acids in TM-6 suggesting that this isoform is not active in ghrelin signal transduction. The cystein residues, N-linked glycosylation sites and potential phosphorylation sites, found in the human GHS-R1a, were also conserved in both chicken isoforms. RT-PCR analysis demonstrated cGHS-R1a and cGHS-R1c mRNA expression in all tissues tested, except liver and pancreas, with highest levels in the pituitary and the hypothalamus. Intermediate levels of expression were detected, in descending order, in the ovary, telencephalon, heart, adrenal gland, cerebellum, and optic lobes whereas low expression was detected in the brainstem, lung, kidney, proventriculus, duodenum, and colon. Very low expression was found in skin, stomach, and muscle. cGHS-R1c was expressed in lower amounts than cGHS-R1a in all analysed tissues. Administration of 1 microM chicken ghrelin to pituitaries in vitro resulted in a down-regulation of both cGHS-R isoforms within 15 min, whereas after 1h levels returned to control values. Growth hormone and corticosterone down-regulated cGHS-R1a and cGHS-R1c mRNA expression within 60 min of exposure, whereas growth hormone-releasing factor 1-29 (1 microM) only reduced cGHS-R1a mRNA expression after 60min. Thyrotropin-releasing hormone (1 microM) did not alter cGHS-R expression.

Involvement of thyrotropin-releasing hormone receptor, somatostatin receptor subtype 2 and corticotropin-releasing hormone receptor type 1 in the control of chicken thyrotropin secretion.

Thyrotropin or thyroid-stimulating hormone (TSH) secretion in the chicken is controlled by several hypothalamic hormones. It is stimulated by thyrotropin-releasing hormone (TRH) and corticotropin-releasing hormone (CRH), whereas somatostatin (SRIH) exerts an inhibitory effect. In order to determine the mechanism by which these hypothalamic hormones modulate chicken TSH release, we examined the cellular localization of TRH receptors (TRH-R), CRH receptors type 1 (CRH-R1) and somatostatin subtype 2 receptors (SSTR2) in the chicken pars distalis by in situ hybridization (ISH), combined with immunological staining of thyrotropes. We show that thyrotropes express TRH-Rs and SSTR2s, allowing a direct action of TRH and SRIH at the level of the thyrotropes. CRH-R1 expression is virtually confined to corticotropes, suggesting that CRH-induced adrenocorticotropin release is the result of a direct stimulation of corticotropes, whereas CRH-stimulated TSH release is not directly mediated by the known chicken CRH-R1. Possibly CRH-induced TSH secretion is mediated by a yet unknown type of CRH-R in the chicken. Alternatively, a pro-opiomelanocortin (POMC)-derived peptide, secreted by the corticotropes following CRH stimulation, could act as an activator of TSH secretion in a paracrine way.

Identification of somatostatin receptors controlling growth hormone and thyrotropin secretion in the chicken using receptor subtype-specific agonists.

Somatostatin (SRIH) functions as an endocrine mediator in processes such as growth, immune resistance and reproduction. Five SRIH receptors (sstr1-5) have been identified in mammals, where they are expressed in both the brain and peripheral tIssues. To study the specific function of each receptor subtype, specific agonists (ag1-5) have been synthesized. The high degree of homology between mammalian and avian SRIH receptors suggests that these agonists might also be used in chickens. In this paper we describe two in vitro protocols (static incubation and perifusion system) to identify the SRIH receptors controlling the secretion of GH and TSH from the chicken pituitary. We found that basal GH or TSH secretion were never affected when SRIH or an agonist (1 microM) were added. SRIH diminished the GH as well as the TSH response to TSH-releasing hormone (TRH; 100 nM) in both systems. Our results have indicated that the SRIH actions at the level of the pituitary are regulated through specific receptor subtypes. In both the static and flow incubations, ag2 lowered the GH response to TRH, whereas stimulated TSH release was diminished by both ag2 and ag5. Ag3 and ag4 tended to increase rather than decrease the responsiveness of both pituitary cell types to TRH in perifusion studies. Our data have indicated that SRIH inhibits chicken pituitary function through sstr2 and sstr5. Only sstr2 seems to be involved in the control of chicken GH release, whereas both sstr2 and sstr5 inhibit induced GH secretion in mammals. The possible stimulatory action of ag3 and ag4 may point towards a species-specific function of sstr3 and sstr4.

Specific detection of type III iodothyronine deiodinase protein in chicken cerebellar purkinje cells.

Because iodothyronine deiodinases play a crucial role in the regulation of the available intracellular T(3) concentration, it is important to determine their cellular localization. In brain, the presence of type III iodothyronine deiodinase (D3) seems to be important to maintain homeostasis of T(3) levels. Until now, no cellular localization pattern of the D3 protein was reported in chicken brain. In this study polyclonal antisera were produced against specific peptides corresponding to the D3 amino acid sequence. Their use in immunocytochemistry led to the localization of D3 in the Purkinje cells of the chicken cerebellum. Both preimmune serum as well as the primary antiserum exhausted with the peptide itself were used as negative controls. Extracts of chick cerebellum and liver were made in the presence of Triton X-100 to solubilize the membrane-bound deiodinases. Using these extracts in Western blot analysis, a band of the expected molecular weight ( approximately 30 kDa) could be detected in both tissues. Using a full-length (32)P-labeled type III deiodinase cRNA probe, we identified a single mRNA species in the cerebellum that was of the exact same size as the hepatic control mRNA (+/-2.4 kb). RT-PCR, followed by subcloning and sequence analysis, confirmed the expression of D3 mRNA in the chicken cerebellum. In this study we provide the first evidence of the presence of the D3 protein in a neuronal cell type, namely Purkinje cells, by means of immunocytochemical staining. We were able to detect a protein fragment corresponding to the expected molecular mass (30 kDa) for type III deiodinase by means of Western blot analysis. RT-PCR as well as Northern blot analysis confirmed the presence of D3 mRNA in the cerebellum.

Changes in thyroid hormone levels in chicken liver during fasting and refeeding.

In chickens, fasting results in increased plasma thyroxine (T(4)) levels and decreased plasma 3,5,3'-triiodothyronine (T(3)) levels. Refeeding, in turn, restores normal plasma T(3) and T(4) levels. The liver is an important tissue for the regulation of circulating thyroid hormone levels. Previous studies demonstrated that the increase in hepatic type III deiodinase in fasted chickens plays a role in the decrease of plasma T(3). Another factor that could be important is the level of T(4) and T(3) uptake by the liver. In mammals, caloric restriction is known to diminish transport of T(4) and T(3) into tissues. The present study examines whether this is also the case in chicken. Four-week-old chickens were subjected to a 24-h starvation period followed by refeeding. Blood and liver samples were collected at the start of refeeding and at different times of refeeding. Thyroid hormone levels were measured directly in plasma and in tissues following extraction. The results demonstrate that intrahepatic T(4) levels are increased and T(3) levels are decreased in fasted compared to ad libitum fed chickens. The parallel changes in plasma and hepatic T(3) and T(4) content demonstrate that T(4) availability in liver tissue is not diminished during fasting, suggesting that in chicken thyroid hormone uptake by the liver is not affected by nutritional status.

Hypothyroidism induces type I iodothyronine deiodinase expression in tilapia liver.

In the current study, the authors examined the effects of experimentally induced hypothyroidism on peripheral thyroid hormone metabolism and growth in two closely related tilapia species: the Nile tilapia (Oreochromis niloticus) and the slower growing black tilapia (Sarotherodon melanotheron). Hypothyroidism, induced by administration of 0.2% methimazole through the food, significantly decreased plasma T(3) and T(4) in both species. This decrease in circulating thyroid hormones was accompanied by an increase in hepatic type II deiodinase (D2) and a decrease in hepatic type III deiodinase (D3). Hepatic type I deiodinase (D1), which is barely expressed in euthyroid tilapia, was significantly upregulated during hypothyroidism. The changes in hepatic D1 and D2 enzyme activity were paralleled by changes in D1 and D2 mRNA levels, indicating pretranslational regulation. Hypothyroidism also resulted in severe growth retardation that was accompanied by an increase in condition factor. Because hyperthyroidism has been shown to decrease the condition factor, these results suggest that thyroid hormones play an essential role in the control of proportional body growth in fish. The authors conclude that (1) hepatic D1 expression is induced by hypothyroidism in tilapia, (2) the changes in hepatic iodothyronine deiodinases during hypothyroidism in tilapia are predominantly regulated at a pretranslational level, and (3) thyroid hormones are involved in the control of proportional body growth in fish.

Effects of rapeseed meal-glucosinolates on thyroid metabolism and feed utilization in rainbow trout.

Two rapeseed meals (RM1 and RM2), containing glucosinolates at a concentration of 26 and 40 micromol/g, respectively, were incorporated at increasing levels (10, 20, and 30% for RM1 and 30 and 50% for RM2) in diets of juvenile rainbow trout. Disturbances in the thyroid axis appeared after 14 days of feeding (with a dietary incorporation level of 10%). The dietary supplementation with T(3) or iodine induced an increase in plasma T(3) levels, compared to that in fish fed the RM diets, and reduced the deleterious effect of RM on growth. When trout were reared in seawater, there was also a slight increase in thyroid hormone levels. TSH treatment had no effect on the thyroid hormone plasma levels. The incorporation of 30% of RM1, which induced a lower dietary content of toxic compounds than RM2, led to a rapid decrease of plasma T(4) and T(3) levels, but growth was affected only after 6 months of feeding. During these studies, the deiodinase activities responded in a complex manner to restore plasma and tissue levels of T(3).

Transcriptional regulation of iodothyronine deiodinases during embryonic development.

A single dose of chicken growth hormone (cGH) or dexamethasone acutely increases circulating T(3) levels in 18-day-old chicken embryos through a reduction of hepatic type III iodothyronine deiodinase (D3). The data in the present study suggest that this decrease in D3 is induced by a direct downregulation of hepatic D3 gene transcription. The lack of effect of cGH or dexamethasone on brain and kidney D3 activity, furthermore suggests that both hormones affect peripheral thyroid hormone metabolism in a tissue specific manner. Dexamethasone administration also results in an increase in brain type II iodothyronine deiodinase (D2) activity and mRNA levels that is also regulated at a transcriptional level. In contrast, however, cGH has no effect on brain D2 activity, thereby suggesting that either GH cannot pass through the blood-brain barrier in chicken or that cGH and dexamethasone regulate thyroid hormone deiodination by different mechanisms. In addition, the very short half-life of D2 and D3 (t(1/2)<1 h) in comparison with the longer half life of type I iodothyronine deiodinase (D1, t(1/2)>8 h), allows for D2 and D3 to play a more prominent role in the acute regulation of peripheral thyroid hormone metabolism than D1.

Synthetic growth hormone secretagogues control growth hormone secretion in the chicken at pituitary and hypothalamic levels.

In the chicken growth hormone (GH) secretion is predominantly controlled by two hormones, thyrotropin-releasing hormone (TRH) and somatostatin (SRIH), respectively stimulating and inhibiting GH release. In view of the hypothesis of a novel GH secretagogue (GHS) in mammals, this specific species was used to further assess the exact function of two nonpeptidyl GHSs-L-692,429 and L-163,255. Both synthetic products stimulate GH secretion directly at the level of the pituitary as shown in in vitro perifusion studies. Plasma GH levels increase within 10-15 min after a single challenge of L-692,429 or L-163,255. A SRIH pretreatment dimishes this GH response. Both GH-releasing peptide mimetics decrease hypothalamic TRH concentrations, whereas SRIH levels are not affected. The novel GHS may therefore control GH secretion both at the level of the pituitary and the hypothalamus. The present article shows that nonpeptidyl mimetics also control GH secretion in nonmammalian species suggesting that the endogenous hormone may be a conserved GH stimulator in several vertebrates. The GH response to GHS in birds may be regulated both directly at the level of the pituitary and by releasing another endogenous GH stimulator (TRH) from the hypothalamus.

Synergetic effect of pimozide and thyrotropin releasing hormone on prolactin and thyrotropin release during the drying off of ewes.

The effect of pimozide and/or TRH was investigated on plasma prolactin, thyrotropin, T(4) and T(3) and udder distension in 38 ewes during drying off by feed restriction. The effect of daily injections of 2mg pimozide (s.c.), combined or not with TRH stimulation (200µg, i.v.) on three different days of the drying off period was examined. Blood samples were taken twice daily in each group for 9 days, while blood sampling on the days of TRH injection was also performed at 0, 15, 30min, and 1, 2 and 4h post-injection. Plasma was assayed for PRL, TSH, T(4) and T(3) levels. Udder distension and mastitis incidence were recorded at the end of the drying off period. TRH and pimozide both resulted in elevated plasma PRL levels and acted in a synergetic way. Udder distension and the incidence of mastitis was only influenced by pimozide. The TSH as well as the T(3) response to TRH was increased in ewes under a continuous influence of pimozide and T(3) peaks following TRH injection occurred earlier than T(4) peaks. The higher effect of pimozide upon TRH stimulated PRL and TSH release at day 8 compared to days 0 and 3 indicates a progressive involvement of dopamine on the inhibition of PRL and the sensitivity of the thyrotrophs to TRH during drying off.

Distribution of somatostatin in the brain and of somatostatin and thyrotropin-releasing hormone in peripheral tissues of the chicken.

Our research group recently presented the distribution of thyrotropin-releasing hormone (TRH) in the chicken brain. In this study we measured somatostatin (SRIH) concentrations in different brain parts and nuclei. The distribution of SRIH and TRH in peripheral tissues was also studied. Although the highest SRIH content was found in endocrine areas like diencephalon and median eminence (ME), high levels were also recorded in brain stem and several hypothalamic nuclei which do not project to the ME. SRIH immunoreactivity was also found within the pituitary. In peripheral tissues, SRIH was mainly present in gonads, thyroid and intestine. Low amounts were found in duodenum, kidney, heart and lung. SRIH concentrations were barely detectable (liver, blood cells) or undetectable (muscle, skin, spleen) in other peripheral tissues investigated. Although TRH was found in all tissues collected, it was also most abundant in brain, pituitary, thyroid and gonads. Our results suggest that also in the chicken SRIH and TRH are implicated in the control of several physiological processes like growth, reproduction and digestion.

Dietary low-glucosinolate rapeseed meal affects thyroid status and nutrient utilization in rainbow trout (Oncorhynchus mykiss).

Two rapeseed (Brassica napus) meals, RM1 and RM2, with two levels of glucosinolates (GLS; 5 and 41 mumol/g DM respectively) were incorporated at the levels of 300 and 500 g/kg of the diets of juvenile rainbow trout (Oncorhynchus mykiss) in replacement of fish meal, and compared with a fish-meal-based diet. A decrease in the digestibility of the DM, protein, gross energy and P was observed with high-rapeseed meal (RM) incorporation. In trout fed on RM-based diets, growth performance was reduced even after only 3 weeks of feeding. Feed efficiency was adversely affected by RM and GLS intake. Protein and energy retention coefficients were significantly lower in fish fed on the diet containing the higher level of GLS. P retention was significantly lower with all the RM-based diets than with the fish-meal diet. Irrespective of the degree of growth inhibition, fish fed on RM-based diets exhibited similar typical features of hypothyroid condition due to GLS intake, expressed by lower plasma levels of triiodothyronine and especially thyroxine and a hyperactivity of the thyroid follicles. This hypothyroidal condition led to a strong adjustment of the deiodinase activities in the liver, the kidney and the brain. A significant increase of the outer ring deiodinase activities (deiodinases type I and II respectively) and a decrease of the inner ring deiodinase activity (deiodinase type III) were observed. It is concluded that the observed growth depression could be attributed to the concomitant presence of GLS, depressing the thyroid function, and of other antinutritional factors affecting digestibility and the metabolic utilization of dietary nutrients and energy.

[The use of laboratory animals or alternatives in fundamental research]. / Het gebruik van proefdieren of alternatieven in het fundamenteel onderzoek.

The use of animals in fundamental and applied research has become a point of controversy. Animals were first used for food or as pets and a historical overview is given. Research was applied or empirical. Fundamental research only developed in the 18th century, without much consideration for animal welfare. It is concluded that even now the use of animals for research remains necessary. However, one should also use alternative methods as often as possible, taking into consideration the three R's: reduction, refinement and replacement. We would like to add the use of comparative research in order to look for animal models in lower vertebrates.

Food deprivation and feeding of broiler chickens is associated with rapid and interdependent changes in the somatotrophic and thyrotrophic axes.

1. In several experiments, hormonal changes in the somatotrophic axis, growth hormone (GH) sensitivity to a GH-secretagogue, thyroid hormones and their metabolising enzymes and plasma glucose levels were measured in relation to food deprivation and reinitiation after a single daily meal in 4- to 5-week-old male broiler chickens. 2. Floor-reared male broiler chickens were fed ad libitum or were restricted to a daily food intake of 40 or 45 g per d from the age of 2 weeks onwards. The daily food allowance was consumed in 0.5 h. 3. Food deprivation increased plasma GH concentrations but decreased GH-dependent variables such as plasma insulin-like growth factor-I and 3,3',5-triiodothyronine (T3) concentrations. Hepatic inner ring deiodinating type III activity was markedly elevated, presumably as a consequence of low hepatic GH receptor numbers, and is thought to be the causal mechanism for the low plasma T3 concentrations. Food intake reversed these variables in a time-related manner. 4. GH pulsatility characteristics, as calculated by deconvolution analysis, revealed profound changes between food restricted and ad libitum fed animals. Chickens deprived of food for about 23.5 h were characterised by an enhanced pulsatile GH release as reflected in the higher GH secretory burst amplitude, GH mass per burst, GH production rate and GH pulse frequency. These variables returned very quickly to normal values after refeeding. 5. In summary these experiments taken together demonstrate very clearly the interdependent and time-related changes of the somatotrophic and thyroid axes upon a single meal in previously food-deprived broiler chickens.

Modulation of the growth hormone-releasing activity of thyrotropin-releasing hormone in the chicken by its gene-related peptide preproTRH((160-169))(Ps4): enhanced somatostatinergic tone?

Recent research demonstrated that endocrine actions of thyrotropin (TSH)-releasing hormone (TRH) are modulated by gene-related products within proTRH. In the present report we show that the growth hormone (GH) response to TRH is clearly inhibited after the preincubation of chicken pituitary glands with preproTRH((160-169))Ps4, whereas the TSH response is not impaired. Binding sites for(125)I-[Tyr(0)]-Ps4 were, however, not detected on chicken pituitary membranes, although (as a control) they were readily detectable on membranes from rat pituitary glands. An indirect action may therefore take place within the pituitary by modulating the action of somatostatin (SRIH), the inhibitor of GH release in the chicken. This hypothesis is strengthened by the observation that Ps4 increases the binding of(125)I-[Tyr(1)]-SRIH to chicken pituitary membranes in a dose-related way. Since Ps4 is also produced by pituitary tissue, this may reflect a local or paracrine action on the regulation of GH release.