RESUMO
Treatment of normal rats with diphenylhydantoin (DPH) decreases serum thyroxine (T4) and triiodothyronine (T3) levels without the anticipated rise in serum thyrotropin (TSH). The present work has studied the intrapituitary conversion of T4 to T3 in male Wistar rats, 200-250 g body weight (BW), treated with DPH 5 mg/100 g BW/day for 8 days. A tracer dose of 3',5'-[125I]T4 (150 microCi) was injected intravenously, and 2 h later hypophyses were removed and homogenized individually at 4 degrees C in ice-cold PBS buffer (pH 7.4). T4 and T3 were extracted in 400 microliters n-butanol:2 N HCl (9:1) and chromatographed in tertiary amyl alcohol:hexane: 1 N ammonia (5:1:6). In 11 untreated control rats, [125I]T3 generated from [125I]T4 deiodination was 35 +/- 6% and intact [125I]T4 was 49 +/- 9% of total chromatographic radioactivity. In 11 DPH-treated rats [125I]T3 increased (p < 0.001) and [125I]T4 decreased (p < 0.02). The DPH effect was blocked in rats treated for 2 days with iopanoic acid 10 mg/100 g BW, though blocking was not seen in rats treated with half the dose of iopanoic acid. In normal rats receiving supplemental doses of T4 (2 micrograms/100 g BW/day for 8 days), DPH similarly increased pituitary 5'-deiodination. Administration of propylthiouracil (PTU) to T4-supplemented rats had no effect on pituitary 5'-deiodination of T4, whereas the addition of DPH to PTU treatment increased [125I]T3 production (p < 0.01). Serum T4 (p < 0.001) and T3 (p < 0.01) were decreased after DPH therapy, while serum and pituitary TSH were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Fenitoína/farmacologia , Hipófise/efeitos dos fármacos , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Animais , Retroalimentação , Masculino , Hipófise/metabolismo , Radioimunoensaio , Ratos , Ratos WistarRESUMO
Acute superior cervical ganglionectomy (SCGx) induces in the rat a supraliminal release of neurotransmitter in the innervated tissues (i.e., thyroid gland). This temporary adrenergic hyperactivity is correlated with a significant depression of the thyroid economy resembling the nonthyroidal illness (NTI) syndrome in the rat, and suggest that the sympathetic nervous system may mediate thyroidal changes in NTI. In order to gain further insight into the thyroidal depression in the NTI syndrome, we studied the thyroidal norepinephrine (NE) turnover in turpentine oil (TURP)-induced NTI syndrome and the role of the cervical ganglia (SCG) in the development of NTI in the rat. TURP administration to sham operated rats induced a rapid and significant fall in plasma T4 and TSH levels, in the thyroidal response to exogenous TSH (TIU) and in the thyroidal NE content compared to controls (sham + saline) (T4: 3.1 +/- 0.3 vs. 5.1 +/- 0.6 micrograms/dl, respectively, mean +/- SE, p less than 0.02; TSH: 1.4 +/- 0.4 vs. 4.7 +/- 1.4 ng/ml, respectively, p less than 0.05; TIU: 92 +/- 14 vs. 201 +/- 20 cpm.microliter thyroid/cpm.mg plasma (T/P ratio), respectively, p less than 0.01; thyroidal NE: 680 +/- 20 vs. 761 +/- 29 pg/mg thyroid, respectively, p less than 0.05). The thyroidal turnover rate of NE, however, was significantly increased in TURP-injected rats compared to controls (122 +/- 13 vs. 86 +/- 10 pg/mg/h, respectively, p less than 0.05). TURP injection to chronic SCGx rats induced a similar fall in plasma TSH compared to controls (SCGx + saline) (1.3 +/- 0.2 vs. 4.3 +/- 1.1 ng/ml, respectively, p less than 0.02); plasma T4 and TIU, however, did not change significantly (T4: 3.4 +/- 0.4 vs. 3.7 +/- 0.3 micrograms/dl, respectively, NS; TIU: 172 +/- 8 vs. 226 +/- 27 T/P ratio, respectively, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Síndromes do Eutireóideo Doente/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Glândula Tireoide/fisiopatologia , Terebintina , Animais , Denervação , Síndromes do Eutireóideo Doente/induzido quimicamente , Gânglios Simpáticos/cirurgia , Ganglionectomia , Masculino , Norepinefrina/metabolismo , Ratos , Ratos Endogâmicos , Glândula Tireoide/inervação , Tireotropina/sangue , Tireotropina/farmacologia , Tiroxina/sangueRESUMO
Thyroid autoregulation has been related to intraglandular content of an unknown putative iodocompund. Data from different laboratories have shown that the thyroid is capable of producing different iodolipids, including iodinated derivatives of arachidonic acid; such as 5-hydroxy-6-iodo-8, 11, 14-eicosatrienoic-delta-lactone (IL-delta). Previous results from our laboratory showed that a semi-purified preparation of iodinated arachidonic acid exerts an inhibitory action in vitro on calf thyroid. In the present studies three purified iodinated derivatives of arachidonic acid were synthesized: IL-delta; 14-iodo-15-hydroxy-5, 8, 11-eicosatrienoic acid (I-OH-A) and its corresponding omega-lactone (IL-omega). Their action on MMI-induced goiter was studied in rats. Administration of MMI to rats during 10 days increased thyroid weight by 124%. This effect was significantly inhibited by the simultaneous injection of 5 micrograms/day of I-OH-A (57% inhibition of MMI action), IL-W (39%), IL-delta (33%) and T3 (95%), while arachidonic acid was without action. No inhibition was found with 1.25 micrograms/day Kl, a dose equivalent to that which could be originated from total dehalogenation of the iodocompounds. These results support the idea that these iodocompounds have an intrinsic biologic activity and that there is a correlation between action and chemical structure. Serum TSH was increased around 15-20 fold after MMI administration. Chronic or acute injection of I-OH-A failed to alter TSH levels, indicating that this iodocompound exerts its action directly on the gland, without altering TSH concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Ácidos Araquidônicos/farmacologia , AMP Cíclico/biossíntese , Bócio/metabolismo , Glândula Tireoide/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Feminino , Homeostase , Ratos , Ratos Endogâmicos , Glândula Tireoide/efeitos dos fármacos , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
The present studies were performed in order to analyze the incorporation of 3H-uridine into RNA and its hormonal regulation as well as the content of total iodine, T3, T4, RNA, DNA and protein in normal and abnormal human thyroid obtained at surgery. The content of protein, RNA and DNA is not significantly changed in follicular adenoma and in adenomatous goiter, RNA labeling from 3H-uridine showed similar values in slices from normal and abnormal glands. TSH and cyclic AMP increased the labeling of RNA in normal tissue but had no effect in the follicular adenoma and adenomatous goiter. A significant decrease in total iodine, T3 and T4 concentration was found in the pathological samples when compared to normals. The present results would suggest that in these patients the biochemical abnormalities lie at a step distal to the TSH receptor and the adenylate cyclase.
Assuntos
Bócio/metabolismo , RNA/biossíntese , Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Uridina/metabolismo , Adenoma/metabolismo , Adolescente , Adulto , Idoso , DNA/análise , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade , RNA/análise , Tireotropina/fisiologia , Tri-Iodotironina/fisiologia , TrítioRESUMO
Los estudios realizados tuvieron como objetivo analizar la incorporacion de 3H-uridina al ARN y su regulacion hormonal, asi como el contenido total de yodo, T3,T4 ARN, ADN y proteina en tiroides humanas normales y anormales, obtenidas por cirurgia. El contenido de proteina, ARN y ADN no se encontro significativamente alterado en el adenoma folicular y en el bocio adenomatoso. La incorporacion de 3H-uridina al ARN de cortes tiroideos fue similar en glandulas normales y anormales. TSH y AMP ciclico estimularon la marcacion del ARN en tejido normal, pero no ejercieron efectos en adenoma folicular y bocio adenomatoso. Una disminucion significativa en la concentracion total de yodo, T3 y T4 fue observada en las muestras patologicas comparadas con las normales. Los resultados obtenidos sugeririan que las alteraciones bioquimicas de los pacientes estudiados estarian localizadas en un paso distal al receptor de la TSH y la adenilciclasa
Assuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , RNA , Glândula Tireoide , Trítio , UridinaRESUMO
The present studies were performed in order to analyze the incorporation of 3H-uridine into RNA and its hormonal regulation as well as the content of total iodine, T3, T4, RNA, DNA and protein in normal and abnormal human thyroid obtained at surgery. The content of protein, RNA and DNA is not significantly changed in follicular adenoma and in adenomatous goiter, RNA labeling from 3H-uridine showed similar values in slices from normal and abnormal glands. TSH and cyclic AMP increased the labeling of RNA in normal tissue but had no effect in the follicular adenoma and adenomatous goiter. A significant decrease in total iodine, T3 and T4 concentration was found in the pathological samples when compared to normals. The present results would suggest that in these patients the biochemical abnormalities lie at a step distal to the TSH receptor and the adenylate cyclase.
RESUMO
Los estudios realizados tuvieron como objetivo analizar la incorporacion de 3H-uridina al ARN y su regulacion hormonal, asi como el contenido total de yodo, T3,T4 ARN, ADN y proteina en tiroides humanas normales y anormales, obtenidas por cirurgia. El contenido de proteina, ARN y ADN no se encontro significativamente alterado en el adenoma folicular y en el bocio adenomatoso. La incorporacion de 3H-uridina al ARN de cortes tiroideos fue similar en glandulas normales y anormales. TSH y AMP ciclico estimularon la marcacion del ARN en tejido normal, pero no ejercieron efectos en adenoma folicular y bocio adenomatoso. Una disminucion significativa en la concentracion total de yodo, T3 y T4 fue observada en las muestras patologicas comparadas con las normales. Los resultados obtenidos sugeririan que las alteraciones bioquimicas de los pacientes estudiados estarian localizadas en un paso distal al receptor de la TSH y la adenilciclasa
Assuntos
Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Humanos , Masculino , Feminino , Estudo Comparativo , Glândula Tireoide , RNA , Trítio , UridinaRESUMO
The role of the sympathetic nervous system in the control of the goitrogenic response was examined in adult male rats subjected to unilateral superior cervical ganglionectomy 12-30 days earlier. A spontaneous goiter as well as an increased thyroid growth after the administration of the goitrogenic agents methylmercaptoimidazole and thyrotropic stimulating hormone (TSH) were found in the ipsilateral lobe. Norepinephrine and epinephrine content decreased significantly by 80 and 31%, and thyroxine (T4) and triiodothyronine (T3) content by 24 and 15%, in the ipsilateral lobe. After the injection of a tracer dose of 125I, percent radioactivity incorporation to diiodotyrosine (DIT) was higher, and that to monoiodotyrosine (MIT) lower, in the ipsilateral lobe; additionally a lower ratio "labeled T3 + T4/labeled DIT" was found in the denervated thyroid lobe. These results suggest that the sympathetic nerve terminals in the thyroid gland modulate the organ's response to circulating TSH.
Assuntos
Simpatectomia , Glândula Tireoide/crescimento & desenvolvimento , Tireotropina/metabolismo , Tiroxina/metabolismo , Animais , Epinefrina/metabolismo , Bócio/etiologia , Radioisótopos do Iodo , Masculino , Metimazol , Norepinefrina/metabolismo , Ratos , Ratos Endogâmicos , Tri-Iodotironina/metabolismoAssuntos
Histamina/farmacologia , Hormônio Liberador de Tireotropina/farmacologia , Tireotropina/metabolismo , Animais , Cimetidina/farmacologia , Dieta , Jejum , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Histidina/farmacologia , Ratos , Ratos EndogâmicosRESUMO
The superior cervical ganglia (SCG) provide sympathetic innervation to the pineal gland, cephalic blood vessels, the choroid plexus, the eye, carotid body and the salivary and thyroid glands. Removal of the ganglia brings about several neuroendocrine changes in mammals, including the disruption of water balance in pituitary stalk-sectioned rats and the alteration of normal photoperiodic control of reproduction and thyroid function in hamsters, ferrets, voles, rams and goats. These effects are commonly attributed to pineal denervation. However, pinealectomy does not always mimic ganglionectomy in its neuroendocrine sequelae. This paper discusses several examples illustrating the differences in ganglia and pineal removal, including the acute and chronic effects of ganglionectomy on the control of thyroid response to TSH in rats. A functionally relevant link between SCG and the hypothalamus occurs in rats, inasmuch as ganglionectomy depresses norepinephrine uptake and increases the number and responses of alpha-adrenoceptors in medial basal hypothalamus. Lastly the SCG are active points of concurrency for hormone signals, as revealed by the metabolic changes induced by steroid and anterior pituitary hormones in these structures, even in the absence of intact preganglionic connections, as well as by the existence of putative receptors for some of the hormones, namely estradiol, testosterone and corticosteroids. The SCG appear to constitute a peripheral neuroendocrine center.
Assuntos
Gânglios Simpáticos/fisiologia , Corticosteroides/metabolismo , Animais , Estradiol/metabolismo , Gânglios Simpáticos/anatomia & histologia , Gânglios Simpáticos/metabolismo , Sistema Hipotálamo-Hipofisário/fisiologia , Norepinefrina/metabolismo , Glândula Pineal/anatomia & histologia , Glândula Pineal/fisiologia , Hormônios Adeno-Hipofisários/metabolismo , Receptores de Superfície Celular/metabolismo , Simpatectomia , Transmissão Sináptica , Testosterona/metabolismo , Glândula Tireoide/inervação , Glândula Tireoide/fisiologiaRESUMO
En el presente trabajo se examino la participacion del sistema simpatico en el control de la respuesta bociogena en ratas sometidas a gangliectomia cervical superior unilateral 12-30 dias antes. En el lobulo tiroideo desnervado se observo un bocio espontaneo, asi como un mayor crecimiento en respuesta a la inyeccion de TSH o metilmercaptoimidazol. En el lobulo desnervado el contenido de noradrenalina y adrenalina disminuyo significativamente en un 80 y 31%, respectivamente, asi como el de tiroxina (T4) y triyodotironina (T3) (24 y 15%, respectivamente). Luego de la inyeccion i.p. de 10 muCi de 125I la incorporacion de radiactividad a diyodotirosina (DIT) fue mayor, v a monoyodotirosina (MIT) menor del lado desnervado, disminuvendo la relacion "T3 y T4/DIT" en forma significativa. Estos resultados sugieren que los terminales simpaticos tiroideos modulan la respuesta del organo a la TSH circulante
Assuntos
Masculino , Animais , Ratos , Simpatectomia , Glândula Tireoide , Tireotropina , TiroxinaAssuntos
Animais , Ratos , Gânglios Simpáticos , Hormônios Adeno-Hipofisários , Glândula Pineal , TestosteronaRESUMO
En el presente trabajo se examino la participacion del sistema simpatico en el control de la respuesta bociogena en ratas sometidas a gangliectomia cervical superior unilateral 12-30 dias antes. En el lobulo tiroideo desnervado se observo un bocio espontaneo, asi como un mayor crecimiento en respuesta a la inyeccion de TSH o metilmercaptoimidazol. En el lobulo desnervado el contenido de noradrenalina y adrenalina disminuyo significativamente en un 80 y 31%, respectivamente, asi como el de tiroxina (T4) y triyodotironina (T3) (24 y 15%, respectivamente). Luego de la inyeccion i.p. de 10 muCi de 125I la incorporacion de radiactividad a diyodotirosina (DIT) fue mayor, v a monoyodotirosina (MIT) menor del lado desnervado, disminuvendo la relacion "T3 y T4/DIT" en forma significativa. Estos resultados sugieren que los terminales simpaticos tiroideos modulan la respuesta del organo a la TSH circulante
Assuntos
Masculino , Animais , Ratos , Glândula Tireoide , Simpatectomia , Tireotropina , TiroxinaAssuntos
Animais , Ratos , Glândula Pineal , Gânglios Simpáticos , Hormônios Adeno-Hipofisários , TestosteronaRESUMO
The role of the sympathetic nervous system in the control of the goitrogenic response was examined in adult male rats subjected to unilateral superior cervical ganglionectomy 12-30 days earlier. A spontaneous goiter as well as an increased thyroid growth after the administration of the goitrogenic agents methylmercaptoimidazole and thyrotropic stimulating hormone (TSH) were found in the ipsilateral lobe. Norepinephrine and epinephrine content decreased significantly by 80 and 31
, and thyroxine (T4) and triiodothyronine (T3) content by 24 and 15
, in the ipsilateral lobe. After the injection of a tracer dose of 125I, percent radioactivity incorporation to diiodotyrosine (DIT) was higher, and that to monoiodotyrosine (MIT) lower, in the ipsilateral lobe; additionally a lower ratio [quot ]labeled T3 + T4/labeled DIT[quot ] was found in the denervated thyroid lobe. These results suggest that the sympathetic nerve terminals in the thyroid gland modulate the organs response to circulating TSH.
RESUMO
The superior cervical ganglia (SCG) provide sympathetic innervation to the pineal gland, cephalic blood vessels, the choroid plexus, the eye, carotid body and the salivary and thyroid glands. Removal of the ganglia brings about several neuroendocrine changes in mammals, including the disruption of water balance in pituitary stalk-sectioned rats and the alteration of normal photoperiodic control of reproduction and thyroid function in hamsters, ferrets, voles, rams and goats. These effects are commonly attributed to pineal denervation. However, pinealectomy does not always mimic ganglionectomy in its neuroendocrine sequelae. This paper discusses several examples illustrating the differences in ganglia and pineal removal, including the acute and chronic effects of ganglionectomy on the control of thyroid response to TSH in rats. A functionally relevant link between SCG and the hypothalamus occurs in rats, inasmuch as ganglionectomy depresses norepinephrine uptake and increases the number and responses of alpha-adrenoceptors in medial basal hypothalamus. Lastly the SCG are active points of concurrency for hormone signals, as revealed by the metabolic changes induced by steroid and anterior pituitary hormones in these structures, even in the absence of intact preganglionic connections, as well as by the existence of putative receptors for some of the hormones, namely estradiol, testosterone and corticosteroids. The SCG appear to constitute a peripheral neuroendocrine center.