Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental rat prolactinomas

Cónsole, Gloria M.; Hereñú, Claudia Beatriz; Camihort, Gisela; Luna, Georgina Cecilia; Bracamonte, María; Morel, Gustavo Ramón; Goya, Rodolfo G.

doi:10.1186/1476-4598-7-13

Cited by 9 publications

(12 citation statements)

References 25 publications

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“…In a previous study we demonstrated that IGF-I gene therapy in estrogen-induced pituitary tumors partially reduced the marked hyperprolactinemia of the animals and also tended to reverse morphometric changes in the lactotrope population [Cónsole et al, 2008]. The present results extend our findings by showing that IGF-I gene therapy in estrogen-induced pituitary tumors is also beneficial for the somatrotropic cell population.…”

Section: Discussionsupporting

confidence: 76%

Effect of Insulin-Like Growth Factor-I Gene Therapy on the Somatotropic Axis in Experimental Prolactinomas

Cónsole¹,

Hereñú

Camihort³

et al. 2008

Cells Tissues Organs

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Insulin-like growth factor-I (IGF-I) provides a physiologic feedback effect within the somatotropic axis. Gene therapy was implemented in young female Sprague-Dawley rats which received 2 pituitary stereotaxic injections of a control recombinant adenoviral vector expressing green fluorescent protein (RAd-GFP) or IGF-I (RAd-IGF-I). The animals were sacrificed 7 days after injection. Previously, on day –23, the experimental groups received subcutaneous implants of 17-β estradiol. Morphometric analysis revealed that the somatotrope cells in estrogen-treated rats without stereotaxic injections showed a significant (p < 0.01) increase in the cell size compared with intact controls (59.9 ± 1.1 vs. 42.9 ± 1.2 μm²) and had a significant (p < 0.05) decrease in cell density with respect to intact animals (10.5 ± 0.1 vs. 19.7 ± 1.7). The treatment of pituitary adenomas with RAd-IGF-I induced a significant (p < 0.05) decrease in cell size with respect to E₂ + RAd-GFP (51.3 ± 0.3 vs. 58.9 ± 0.3 μm²) and no changes in cell density compared with RAd-GFP-injected animals (12.8 ± 1.7 vs. 10.5 ± 0.1). Serum growth hormone was higher (p < 0.01) in estrogen-treated animals versus controls (146.7 ± 6 vs. 73.9 ± 9 ng/ml). In rats carrying estrogen-induced adenomas, RAd-IGF-I injection induced a significant (p < 0.05) decrease in serum growth hormone compared to RAd-GFP-injected animals (107.5 ± 7 vs. 142.4 ± 9 ng/ml). IGF-I gene therapy appears to be an effective approach for the treatment of experimental somatomammotropic pituitary tumors and could be potentially useful as an adjuvant of conventional therapies.

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Section: Discussionsupporting

confidence: 76%

Effect of Insulin-Like Growth Factor-I Gene Therapy on the Somatotropic Axis in Experimental Prolactinomas

Cónsole¹,

Hereñú

Camihort³

et al. 2008

Cells Tissues Organs

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“…Bearing in mind the common embryological origin of lactotropic and somatotropic cells, we suggest that there is a possibility that chronic hyperprolactinemia may suppress GH secretion. On the other hand, there is some evidence that IGF-1 gene therapy reverses morphological changes and reduces hyperprolactinemia in rats with prolactinomas [20].…”

Section: Correlation Of Prolactin Levels and Variables Within The Stumentioning

confidence: 99%

Obesity and hypercholesterolemia in patients with prolactinomas: Could DHEA-S and growth hormone be the missing link?

et al. 2016

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DHEA-S, GH and prolactin remained significant even after adjustment for BMI. GH and IGF-I were associated with BMI and LDL cholesterol, but the association diminished after adjustment for serum prolactin.Conclusions: Prevalence of obesity is four times higher in patients with prolactinomas than in patients with nonfunctional adenomas. Higher DHEA-S and lower GH levels in patients with prolactinomas may have an important role in prolactin-induced metabolic effects. Further studies are needed.3

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“…Although important advances have been made in the treatment of pituitary tumors with surgery and radiotherapy as well as pharmacological approaches, a fully marked hyperprolactinemia of the animals and also tended to reverse phenotype changes in the lactotrope population [Cónsole et al, 2008]. The mechanism by which pituitary overexpression of IGF-I inhibits lactotropic cell growth and PRL secretion is not clear.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently demonstrated that in vivo delivery of the gene for rat IGF-I in estrogen-induced rat prolactinomas was able to partially reverse hyperprolactinemia and restore lactotrope [Cónsole et al, 2008] and somatotrope cell morphology . In the present study, we expanded our investigations into the actions of IGF-I gene therapy in estrogen-induced pituitary tumors by assessing the effect of this treatment on other endocrine pituitary cell populations in these tumors.…”

mentioning

confidence: 99%

Morphological Changes Induced by Insulin-Like Growth Factor-I Gene Therapy in Pituitary Cell Populations in Experimental Prolactinomas

Camihort¹,

Hereñú

Luna

et al. 2009

Cells Tissues Organs

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In previous studies, we assessed the effects of intrapituitary injection of a recombinant adenoviral vector (RAd) harboring the cDNA for rat insulin-like growth factor type I (RAd-IGF-I) on the lactotrope and somatotrope populations in estrogen-induced prolactinomas. In the present study, we aimed to confirm these findings and further analyze the effect of transgenic RAd-IGF-I on the other pituitary cell populations in female rats. All animals except the intact group (no estrogen and no stereotaxic injection) received subcutaneous estrogen for 30 days, and the groups which received RAd-IGF-I or RAd expressing green fluorescent protein (control) were additionally treated with the appropriate vectors on experimental day 0. The RAd-IGF-I group showed a significant decrease in serum growth hormone and prolactin levels and lactotrope and somatotrope cell size induced by estrogen treatment. Cell density was not affected by 7 days of IGF-I gene therapy. Estrogen had an inhibitory effect on thyrotrope cell density, whereas with RAd-IGF-I there was a nonsignificant trend towards restoration of cell density, without changes in cell size. RAd-IGF-I treatment decreased corticotrope cell size without changing cell density. Estrogen decreased gonadotrope cell size and density, which was reversed by RAd-IGF-I. We conclude that in estrogen-induced pituitary tumors, IGF-I gene therapy has inhibitory effects on the lactotrope, somatotrope and corticotrope populations, while reversing the effect of estrogen on gonadotropic cells.

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Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental rat prolactinomas

Cited by 9 publications

References 25 publications

Effect of Insulin-Like Growth Factor-I Gene Therapy on the Somatotropic Axis in Experimental Prolactinomas

Effect of Insulin-Like Growth Factor-I Gene Therapy on the Somatotropic Axis in Experimental Prolactinomas

Obesity and hypercholesterolemia in patients with prolactinomas: Could DHEA-S and growth hormone be the missing link?

Morphological Changes Induced by Insulin-Like Growth Factor-I Gene Therapy in Pituitary Cell Populations in Experimental Prolactinomas

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