The integrity of the thymus during the first
week of life is necessary for a proper maturation of the
pituitary-gonadal axis as revealed by the significantly
reduced levels of circulating gonadotropins in
congenitally athymic (nude) mice. In the present work
we studied the impact of athymia and the effect of
neonatal thymulin gene therapy on the pituitaries of
adult nude mice. Also circulating thymulin and
gonadotropin levels were evaluated. We used an
adenoviral vector expressing a synthetic gene for the
thymic peptide thymulin (metFTS) termed RAd-FTS.
On postnatal day 1, each experimental heterozygous
(nu/+) and homozygous (nu/nu) pup of both sexes
received a single bilateral i.m. injection of RAd-FTS or
RAd-GFP/TK, a control vector expressing green
fluorescent protein. On postnatal days 51-52, mice were
bled and sacrificed, their pituitaries were immediately
dissected, fixed and immunostained. Morphometry was
performed by means of an image analysis system. The following parameters were calculated: volume density
(VD: cell area/reference area), cell density (CD: number
of cells/reference area), and cell size (expressed in μm2).
Serum thymulin levels were measured by a bioassay and
gonadotropin levels were assayed by RIA. It was
observed that neonatal thymulin gene therapy in the
athymic mice restored their serum thymulin levels and
prevented the reduction in circulating gonadotropin
levels. The histometrical analysis revealed that the
treatment prevented the reduction in gonadotrope CD
and the VD in athymic mice. Our data suggest that
thymulin gene therapy may be an effective strategy to
approach reproductive deficits associated with endocrine thymus dysfunction