Morphological restoration of pituitary thyrotrope population by thymulin gene therapy in nude mice

Thymulin secretion is strongly influenced by the neuroendocrine system. Thymulin also possesses hypophysiotropic activity which suggests that this metallopeptide may play an important role in thymic‐pituitary axis, particularly during early life. The aim of the present study was to evaluate the histomorphological changes of neonatal thymulin gene therapy on the thyrotrope population of adult nude mice. We used an adenoviral vector expressing a synthetic gene for thymulin 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, a control vector. On postnatal days 51–52, the mice were sacrificed, and their pituitaries were immediately dissected, fixed and immunostained. Morphometry was performed by means of an image‐analysis system. The calculated parameters were: volume density (VD), cell density (CD), and cell size (μm 2 ). Serum thymulin levels were measured by a bioassay. It was observed that neonatal thymulin gene therapy in the athymic mice restored their serum thymulin levels. The histometrical analysis revealed that the treatment prevented the reduction in thyrotrope cell, volume density, and cell size in athymic mice. Our data suggests that thymulin gene therapy may be an effective strategy to approach deficits associated with endocrine thymus dysfunction. Research support provided by Universidad Adventista del Plata.