RESUMO
Rapid actions of T3 on TSH synthesis in posttranscriptional steps, such as polyadenylation and translation rate, have already been described. The focus of this paper was to characterize rapid actions of T3 on TSH secretion and the involvement of actin and microtubule cytoskeleton in this process. For that, sham-operated (SO) and thyroidectomized (Tx) rats were subjected to acute or chronic treatment with T3. We observed a disarrangement in microtubule and actin cytoskeletons and an increase in Tshb mRNA levels in Tx rats, whereas the total TSH protein content was reduced in the pituitary gland as a whole, but increased in the secretory granules close to the plasma membrane of thyrotrophs, as well as in the extracellular space. The acute T3 dose promoted a rapid increase and redistribution of TSH secretory granules throughout the cytoplasm, as well as a rearrangement in actin and microtubule cytoskeletons. The T3 chronic treatment outcome reinforces the acute effects observed and, additionally, evinces an increase in the α-tubulin content and a rearrangement in microtubule cytoskeleton. Thus, T3 is able to rapidly suppress TSH secretion and, in parallel, to promote a rearrangement in actin and microtubules assembly throughout the pituitary gland, effects that seem to be independent from each other.
Assuntos
Citoesqueleto/fisiologia , Vesículas Secretórias/fisiologia , Tireotrofos/citologia , Tireotropina/metabolismo , Tri-Iodotironina/farmacologia , Actinas/metabolismo , Animais , Masculino , Ratos , Ratos Wistar , Tireoidectomia , Tireotrofos/metabolismo , Tireotropina Subunidade beta/genética , Tireotropina Subunidade beta/metabolismoRESUMO
There is evidence of the existence of a bidirectional relationship between the thymus gland and the thyroid axis. Since the thymic peptide thymulin possesses hypophysiotropic activity, we undertook the task of assessing the histomorphometric changes induced by thymulin deficiency on the thyrotrope population of normal mice and the action of neonatal thymulin gene therapy on the thyrotropin (TSH)-cells of nude mice. C57BL/6 mice were subjected to immunoneutralization of circulating thymulin from postnatal day 1 to the end of the study (postnatal day 32) by intraperitoneal injections of rabbit anti-factor thymulin serum (α-FTS) and normal rabbit serum in controls. Also, neonatal thymulin gene therapy was implemented in athymic nude mice using an adenoviral vector expressing a gene for thymulin (RAd-FTS). On postnatal day 1, heterozygous (nu/+) and homozygous (nu/nu) pups received a single bilateral intramuscular (i.m.) injection of either RAd-FTS or RAd-GFP (the latter being the control vector). The pituitaries were immunostained for TSH. Thymulin immunoneutralization severely reduced serum thymulin (p < 0.01). We detected a significant (p < 0.05) decrease in cell size (CS) and volume density (VD) with a nonsignificant decrease in cell density (CD) in C57BL/6 in both males and females. A single neonatal i.m. injection of RAd-FTS markedly increased the circulating levels of serum thymulin in the athymic mice and increased the CD (p < 0.05), CS (p < 0.01) and VD (p < 0.01) of the thyrotrope population in nu/nu mice. Thyroid histology was not affected. Our results suggest a possible modulating effect of thymulin on the thyrotrope population.
Assuntos
Fator Tímico Circulante/genética , Tireotrofos/citologia , Animais , Contagem de Células , Feminino , Terapia Genética , Vetores Genéticos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Fator Tímico Circulante/deficiência , Timo/anatomia & histologia , Timo/metabolismo , Tireotrofos/metabolismoRESUMO
The physiology and behavior of viscacha vary along the year according to the modifications of environmental signals such as the photoperiod length, temperature, rainfall pattern, food composition, and social interactions. The pituitary pars distalis thyrotrophs (TSH cells) of male viscacha were immunohistochemically identified, and the morphometric parameters: percentage of immunopositive area (% IA), cell percentage in pars distalis (% PDC), number of cells per reference area (no. cells/RA), and major cellular and nuclear diameters were analyzed. Three different groups of adult male viscachas were used: (1) captured in their natural habitat during the year, (2) melatonin-administered, and (3) castrated. The thyrotrophs were localized in the ventromedial sector, mainly in the pars distalis cephalic extreme. They were oval or pyramidal in shape, and their immunostaining intensity was heterogeneous. The % IA, % PDC, and no. cells/RA exhibited a significant decrease in June-July (winter, gonadal regression period) in relation to February-March (summer-early autumn, reproductive period), and they were recovered in August-September (later winter-early spring, gonadal recovery period). No morphometric variations of TSH cells were observed in melatonin-treated animals, whereas a decrease of the % IA, % PDC, and no. cells/RA was observed in castrated animals in relation to the intact animals. Our results show TSH cell morphometric variations during the year in agreement with the animal's different physiological conditions during the reproductive cycle, and probably in response to the environmental signals changes. Melatonin does not have a direct effect on the TSH cells. However, castration modifies some thyrotroph morphometric parameters, reinforcing the hypothesis that androgens affect the cells activity.
Assuntos
Melatonina/fisiologia , Adeno-Hipófise/citologia , Estações do Ano , Tireotrofos/citologia , Adaptação Fisiológica , Androgênios/fisiologia , Animais , Castração , Contagem de Células , Meio Ambiente , Imuno-Histoquímica , Masculino , Adeno-Hipófise/crescimento & desenvolvimento , Adeno-Hipófise/metabolismo , Roedores/anatomia & histologia , Roedores/fisiologia , Testículo/fisiologia , Tireotrofos/metabolismoRESUMO
Thymulin is a thymic hormone involved in several aspects of intra- and extrathymic T-cell differentiation. Thymulin also possesses hypophysiotropic activity which suggests that this metallopeptide may play an important role in thymus-pituitary communication, particularly during early life. The aim of the present study was to evaluate the impact of serum thymulin suppression from birth to peripuberty on the morphology of different pituitary cell populations in prepubertal C57Bl/6 mice. Animals were submitted to immunoneutralization of circulating thymulin from postnatal day 1 to the end of the study (age 32 days). From their 1st day of life, the animals were submitted to a protocol of intraperitoneal injections of rabbit anti-thymulin serum (alpha-FTS) and normal rabbit serum (NRS) in the controls. On their 33rd day of life, the animals were killed and their pituitaries were immediately dissected, fixed and immunostained using the EnVision system with primary antibodies against growth hormone, thyrotropin, corticotropin, gonadotropins and prolactin. Morphometry was performed by means of an image analysis system. The following parameters were calculated: volume density = Sigma cell area/reference area (RA); cell density (CD) = number of cells/RA, and cell size (expressed in microm2). Serum thymulin was measured by a rosette bioassay while pituitary hormones were assayed by radioimmunoassay. Serum prolactin, luteinizing hormone, follicle-stimulating hormone, growth hormone and thyroid-stimulating hormone were significantly lower in the alpha-FTS animals of either sex compared with the corresponding NRS counterparts. The somatotrope, lactotrope and corticotrope populations showed a significant decrease in CD, while cell hypertrophy was observed in some of the pituitary cell populations of the alpha-FTS group compared to the NRS group. In the alpha-FTS group, there were sex differences in the morphometric changes observed. Our results suggest that serum thymulin plays a significant role during early life in the postnatal maturation of endocrine cells of the mouse anterior pituitary gland.