INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
artículos
Título:
Morphological Effects on the Corticotrope Population by Thymulin Gene Therapy in Nude
Autor/es:
MARTINES E; REGGIANI PC; SCHWERDT JI; GOYA RG; CONSOLE GM
Revista:
HISTOLOGY AND HISTOPATHOLOGY
Editorial:
F HERNANDEZ
Referencias:
Año: 2011 vol. 26 p. 471 - 479
ISSN:
0213-3911
Resumen:
Summary. 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: S cell area/reference area), cell density (CD:
number of cells/reference area), and cell surface (CS:
expressed in ìm2). 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.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: S cell area/reference area), cell density (CD:
number of cells/reference area), and cell surface (CS:
expressed in ìm2). 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.S cell area/reference area), cell density (CD:
number of cells/reference area), and cell surface (CS:
expressed in ìm2). 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.2). 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.