Background: Insulin-like Growth Factor1 (IGF1) is a powerful neuroprotective molecule.
We have previously shown that short-term hypothalamic IGF1 gene therapy restores tuberoinfundibular
dopaminergic neuron function in aging female rats.
Objective: Our aim was to implement long-term IGF-I gene therapy in pituitary prolactinomas in senile
Methods: Here, we assessed the long-term effect of IGF1 gene therapy in the hypothalamus of young
(4 mo.) and aging (24 mo.) female rats carrying spontaneous pituitary prolactinomas. We constructed
and injected a Helper-Dependent (HD) adenovector expressing the gene for rat IGF1 or the reporter
red fluorescent protein DsRed. Ninety-one days post vector injection, all rats were sacrificed and their
brains and pituitaries fixed. Serum prolactin (PRL), Estrogen (E2) and progesterone (P4), as well as
hypothalamic IGF1 content, were measured by RIA. Anterior pituitaries were immunostained with an
anti-rat PRL antibody and submitted to morphometric analysis.
Results: DsRed expression in the Mediobasal Hypothalamus (MBH) was strong after the treatment in
the DsRed group while IGF1 content in the MBH was higher in the IGF1 group. The IGF1 treatment
affected neither pituitary weight nor PRL, E2 or P4 serum levels in the young rats. In the old rats,
IGF1 gene therapy reduced gland weight as compared with intact counterparts and tended to reduce
PRL levels as compared with intact counterparts. The treatment significantly rescued the phenotype of
the lactotropic cell population in the senile adenomas.
Conclusion: We conclude that long-term hypothalamic IGF1 gene therapy is effective to rescue spontaneous
prolactinomas in aging female rats.