The thymulin-lactotropic axis in rodents: thymectomy, immunoneutralization and gene transfer studies.

OBJECTIVES: There is clear evidence on the existence of a thymus-pituitary axis which seems to be particularly important during perinatal life. In particular, the thymic peptide thymulin has been shown to be a relevant player in thymus-pituitary communication. Our goal was to explore the effect of thymulin on circulating prolactin (PRL) levels in different animal models. To this end we undertook a series of experiments in rats and mice, implementing adult thymectomy, thymulin immunoneutralization in normal C57BL/6 mice and neonatal thymulin gene therapy in nude mice. METHODS: We assessed the impact of the above manipulations on PRL secretion and lactotrope morphology by measuring serum PRL by radioimmunoassay and by performing morphometric analysis of the lactotropic cell population in the anterior pituitary gland. RESULTS: Adult thymectomy in female rats slightly increased serum PRL, an effect that was partially reversed by thymulin gene therapy. In mice, thymulin immunoneutralization from birth to age 32 days reduced serum PRL both in males and females. Thymulin immunoneutralization induced a significant (p < 0.01) decrease in lactotrope cell density (CD) and volume density (VD) without changes in cell size (CS). Neonatal thymulin gene therapy markedly increased serum thymulin (p < 0.01) and lactotrope CD, CS and VD in nude mice of both sexes. CONCLUSIONS: Our findings suggest a modulatory effect of thymulin on the lactotrope cell population and on serum PRL, particularly during early life.

Role of thymulin on the somatotropic axis in vivo.

AIMS: There is clear evidence for the existence of a bi-directional thymus-somatotropic axis and several studies suggest that the thymic peptide thymulin may be involved in this communication. We undertook to assess the impact of serum thymulin immunoneutralization in C57BL/6 mice and that of neonatal thymulin gene therapy (NTGT) in nude mice on body weight (BW) gain and on the histomorphometric profile of the somatotrope population. MAIN METHODS: Immunoneutralization of thymulin was done from postnatal day 1 to 35 by i.p. injections of rabbit anti-thymulin serum (α-FTS) and normal rabbit serum (NRS) in controls. NTGT was implemented in nudes using an adenoviral vector expressing a synthetic gene for thymulin (RAd-FTS). On postnatal day 1, heterozygous (nu/+) and homozygous (nu/nu) pups received a single bilateral i.m. injection either RAd-FTS or RAd-GFP (a control vector expressing green fluorescent protein). BW gain was recorded and at the end of the study the pituitaries were immunostained for growth hormone (GH). Serum GH and thymulin were determined by radioimmunoassay and bioassay, respectively. KEY FINDINGS: Thymulin immunoneutralization induced a significant decrease in BW gain, serum GH and somatotrope cell density as well as an increase in somatotrope cell size. NTGT markedly increased BW gain, serum thymulin (P<0.01) and somatotrope cell and volume density in nu/nu mice. SIGNIFICANCE: Our results suggest that thymulin plays a relevant physiological role on the thymus-somatotropic axis in mice.

Neonatal thymulin gene therapy in nude mice: Effects on the morphology of the pituitary corticotrope population.

The integrity of the thymus during early life is necessary for a proper maturation of the neuroendocrine system, including the adrenal axis. The thymic metallopeptide thymulin seems to be a central physiologic mediator of thymus-pituitary communication. Furthermore, neonatal thymulin gene therapy has been shown to prevent the typical alterations of gonadotrophic cell number and morphology and serum gonadotropin levels in nude female mice. In the present study we assessed the impact of athymia and the effect of neonatal thymulin gene therapy on the corticotropic cell population in nude mice. The effect of thymulin administration to adult nudes on their hypothalamic content of corticotropin-releasing hormone (CRH) and the adrenal content of corticosterone was also determined. We used an adenoviral vector expressing a synthetic gene for the thymic peptide thymulin (metFTS) termed RAd-FTS. On postnatal day 1 or 2, heterozygous (nu/+) and homozygous (nu/nu) pups of both sexes received a single bilateral i.m. injection of RAd-FTS or RAd-GFP, a control vector. On postnatal day 71, mice were bled and sacrificed, and their pituitaries were immediately dissected, fixed and immunostained for corticotropin. Morphometry was performed by means of an image-analysis system. The following parameters were calculated: volume density (VD: Σ cell area/reference area), cell density (CD: number of cells/reference area), and cell surface (CS: expressed in µm²). Serum thymulin levels were measured by a bioassay, and CRH as well as corticosterone were determined by IRMA and RIA, respectively. Neonatal thymulin gene therapy in the athymic mice restored their serum thymulin levels and increased corticotrope CD, VD and CS in both control and athymic mice. Athymic mice showed only a marginal reduction in corticotrope CD, VD and CS. In these mutants hypothalamic CRH content was slightly increased, whereas adrenal corticosterone tended to be lower. Thymulin administration to adult mice tended to reverse these changes. Our results suggest a possible modulating effect of thymulin on the corticotrope population and the adrenal gland, confirming the existence of a bidirectional thymus-pituitary-adrenal axis.

Thymulin gene therapy prevents the histomorphometric changes induced by thymulin deficiency in the thyrotrope population of mice.

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.

Mães de sonhos: uma proposta de reflexão e intervenção nas relações familiares / Mothers of dreams: a proposal of reflection and intervention into family relations

O presente artigo realiza uma análise qualitativa e quantitativa da estreita intersecção entre autoconhecimento, autoestima e as relações familiares de algumas mulheres residentes na cidade de Sud Mennucci, no estado de São Paulo, cujos filhos estavam matriculados na entidade municipal Casa de Assistência à Criança e ao Adolescente - Sonho Meu - no decorrer de 2007. Além disso, através do referido projeto, estas mulheres tiveram a oportunidade de construir um grupo de apoio, no qual fortaleceram a sua saúde psíquica e o exercício dos papéis sociais de: mãe, esposa, ser humano e profissional. Elas também aprenderam algumas estratégias relevantes à mudança comportamental. A metodologia escolhida foi bastante diversificada para atender às necessidades do grupo participante e de organização profissional, além de contar com o suporte de três áreas de conhecimento: Serviço Social, Psicologia e Pedagogia, condensadas nos departamentos de Assistência Social e de Saúde do referido município. Os resultados atingidos foram de grande valia para as relações familiares do público-alvo e para todos os profissionais envolvidos, quer seja direta ou indiretamente na execução do mesmo. A família é vista como a célula-tronco da nossa sociedade, na qual os valores morais, os princípios éticos, a cultura, a educação e outros conceitos são transmitidos e consolidados ao longo de gerações. Mas sabemos que uma entidade formadora de tamanha magnitude tem algumas lacunas, as quais foram abordadas na expectativa de serem sanadas, buscando a promoção e qualidade dos vínculos afetivos familiares através destas mulheres.(AU)

Mães de sonhos: uma proposta de reflexão e intervenção nas relações familiares / Mothers of dreams: a proposal of reflection and intervention into family relations

O presente artigo realiza uma análise qualitativa e quantitativa da estreita intersecção entre autoconhecimento, autoestima e as relações familiares de algumas mulheres residentes na cidade de Sud Mennucci, no estado de São Paulo, cujos filhos estavam matriculados na entidade municipal Casa de Assistência à Criança e ao Adolescente - Sonho Meu - no decorrer de 2007. Além disso, através do referido projeto, estas mulheres tiveram a oportunidade de construir um grupo de apoio, no qual fortaleceram a sua saúde psíquica e o exercício dos papéis sociais de: mãe, esposa, ser humano e profissional. Elas também aprenderam algumas estratégias relevantes à mudança comportamental. A metodologia escolhida foi bastante diversificada para atender às necessidades do grupo participante e de organização profissional, além de contar com o suporte de três áreas de conhecimento: Serviço Social, Psicologia e Pedagogia, condensadas nos departamentos de Assistência Social e de Saúde do referido município. Os resultados atingidos foram de grande valia para as relações familiares do público-alvo e para todos os profissionais envolvidos, quer seja direta ou indiretamente na execução do mesmo. A família é vista como a célula-tronco da nossa sociedade, na qual os valores morais, os princípios éticos, a cultura, a educação e outros conceitos são transmitidos e consolidados ao longo de gerações. Mas sabemos que uma entidade formadora de tamanha magnitude tem algumas lacunas, as quais foram abordadas na expectativa de serem sanadas, buscando a promoção e qualidade dos vínculos afetivos familiares através destas mulheres.

The present article conducts a qualitative and quantitative analysis of the intersection between the self-knowledge, self-esteem and family relations of women living in the city of Sud Mennucci, in the state of São Paulo, whose children were enrolled during the year 2007 in a municipal entity that provides assistance for children and adolescents, called Sonho Meu (My Dream). Through this project, these women could build a support group in which they strengthened their psychic health and the performance of the social roles of mother, wife, human being and professional. They also learnt some strategies that favored behavior changes. The chosen methodology was diversified in order to meet the group's needs and also those of the professional organization, and was supported by three areas of knowledge: Social Work, Psychology and Pedagogy, concentrated in the Social Assistance and Health Departments of the city of Sud Mennucci. The results were extremely valuable to the family relations of the target audience and also to every professional involved in this project, directly or indirectly. The family is seen as the stem cell of our society, in which the moral values, ethical principles, culture, education and other concepts are transmitted and solidified across generations. But we also know that an entity of such magnitude has some gaps, which were approached in order to be solved, searching for the promotion and quality of the affective family bonds through these women.