Sex differences in the pituitary transforming growth factor-β1 system: Studies in a model of resistant prolactinomas
Dopamine and estradiol interact in the regulation of lactotroph cell proliferation and prolactin secretion. Ablation of the dopamine D2 receptor gene (Drd2-/-) in mice leads to a sexually dimorphic phenotype of hyperprolactinemia and pituitary hyperplasia, which is stronger in females. TGF-β1 is a k...
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2013
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v154_n11_p4192_Recouvreux http://hdl.handle.net/20.500.12110/paper_00137227_v154_n11_p4192_Recouvreux |
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paper:paper_00137227_v154_n11_p4192_Recouvreux2023-06-08T14:36:17Z Sex differences in the pituitary transforming growth factor-β1 system: Studies in a model of resistant prolactinomas binding protein dopamine estrogen furin kallikrein kallikrein 1 matrix metalloproteinase thrombospondin 1 transforming growth factor beta binding protein transforming growth factor beta1 unclassified drug animal experiment animal model article controlled study down regulation female gene expression genotype hypophysis male mouse nonhuman priority journal prolactinoma sex difference Animals Female Gene Expression Regulation Genotype Integrins Male Mice Mice, Knockout Pituitary Gland Pituitary Neoplasms Prolactinoma Receptors, Dopamine D2 Sex Factors Thrombospondin 1 Tissue Kallikreins Transforming Growth Factor beta1 Dopamine and estradiol interact in the regulation of lactotroph cell proliferation and prolactin secretion. Ablation of the dopamine D2 receptor gene (Drd2-/-) in mice leads to a sexually dimorphic phenotype of hyperprolactinemia and pituitary hyperplasia, which is stronger in females. TGF-β1 is a known inhibitor of lactotroph proliferation. TGF-β1 is regulated by dopamine and estradiol, and it is usually down-regulated in prolactinoma experimental models. To understand the role of TGF-β1 in the gender-specific development of prolactinomas in Drd2-/- mice, we compared the expression of different components of the pituitary TGF-β1 system, including active cytokine content, latent TGF-β-binding protein isoforms, and possible local TGF-β1 activators, in males and females in this model. Furthermore,weevaluated the effects of dopamine and estradiol administration to elucidate their role in TGF-β1 system regulation. The expression of active TGF-β1, latent TGF-β-binding protein isoforms, and several putative TGF-β1 activators evaluated was higher in male than in female mouse pituitary glands. However, Drd2-/- female mice were more sensitive to the decrease in active TGF-β1 content, as reflected by the down-regulation of TGF-β1 target genes. Estrogen and dopamine caused differential regulation of several components of the TGF-β1 system. In particular, we found sex- and genotype- dependent regulation of active TGF-β1 content and a similar expression pattern for 2 of the putative TGF-β1 activators, thrombospondin-1 and kallikrein-1, suggesting that these proteins could mediate TGF-β1 activation elicited by dopamine and estradiol. Our results indicate that (1) the loss of dopaminergic tone affects the pituitary TGF-β1 system more strongly in females than in males, (2) males express higher levels of pituitary TGF-β1 system components including active cytokine, and (3) estradiol negatively controls most of the components of the system. Because TGF-β1 inhibits lactotroph proliferation, we propose that the higher levels of the TGF-β1 system in males could protect or delay the development of prolactinomas in Drd2-/- male mice. Copyright © 2013 by The Endocrine Society. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v154_n11_p4192_Recouvreux http://hdl.handle.net/20.500.12110/paper_00137227_v154_n11_p4192_Recouvreux |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
binding protein dopamine estrogen furin kallikrein kallikrein 1 matrix metalloproteinase thrombospondin 1 transforming growth factor beta binding protein transforming growth factor beta1 unclassified drug animal experiment animal model article controlled study down regulation female gene expression genotype hypophysis male mouse nonhuman priority journal prolactinoma sex difference Animals Female Gene Expression Regulation Genotype Integrins Male Mice Mice, Knockout Pituitary Gland Pituitary Neoplasms Prolactinoma Receptors, Dopamine D2 Sex Factors Thrombospondin 1 Tissue Kallikreins Transforming Growth Factor beta1 |
| spellingShingle |
binding protein dopamine estrogen furin kallikrein kallikrein 1 matrix metalloproteinase thrombospondin 1 transforming growth factor beta binding protein transforming growth factor beta1 unclassified drug animal experiment animal model article controlled study down regulation female gene expression genotype hypophysis male mouse nonhuman priority journal prolactinoma sex difference Animals Female Gene Expression Regulation Genotype Integrins Male Mice Mice, Knockout Pituitary Gland Pituitary Neoplasms Prolactinoma Receptors, Dopamine D2 Sex Factors Thrombospondin 1 Tissue Kallikreins Transforming Growth Factor beta1 Sex differences in the pituitary transforming growth factor-β1 system: Studies in a model of resistant prolactinomas |
| topic_facet |
binding protein dopamine estrogen furin kallikrein kallikrein 1 matrix metalloproteinase thrombospondin 1 transforming growth factor beta binding protein transforming growth factor beta1 unclassified drug animal experiment animal model article controlled study down regulation female gene expression genotype hypophysis male mouse nonhuman priority journal prolactinoma sex difference Animals Female Gene Expression Regulation Genotype Integrins Male Mice Mice, Knockout Pituitary Gland Pituitary Neoplasms Prolactinoma Receptors, Dopamine D2 Sex Factors Thrombospondin 1 Tissue Kallikreins Transforming Growth Factor beta1 |
| description |
Dopamine and estradiol interact in the regulation of lactotroph cell proliferation and prolactin secretion. Ablation of the dopamine D2 receptor gene (Drd2-/-) in mice leads to a sexually dimorphic phenotype of hyperprolactinemia and pituitary hyperplasia, which is stronger in females. TGF-β1 is a known inhibitor of lactotroph proliferation. TGF-β1 is regulated by dopamine and estradiol, and it is usually down-regulated in prolactinoma experimental models. To understand the role of TGF-β1 in the gender-specific development of prolactinomas in Drd2-/- mice, we compared the expression of different components of the pituitary TGF-β1 system, including active cytokine content, latent TGF-β-binding protein isoforms, and possible local TGF-β1 activators, in males and females in this model. Furthermore,weevaluated the effects of dopamine and estradiol administration to elucidate their role in TGF-β1 system regulation. The expression of active TGF-β1, latent TGF-β-binding protein isoforms, and several putative TGF-β1 activators evaluated was higher in male than in female mouse pituitary glands. However, Drd2-/- female mice were more sensitive to the decrease in active TGF-β1 content, as reflected by the down-regulation of TGF-β1 target genes. Estrogen and dopamine caused differential regulation of several components of the TGF-β1 system. In particular, we found sex- and genotype- dependent regulation of active TGF-β1 content and a similar expression pattern for 2 of the putative TGF-β1 activators, thrombospondin-1 and kallikrein-1, suggesting that these proteins could mediate TGF-β1 activation elicited by dopamine and estradiol. Our results indicate that (1) the loss of dopaminergic tone affects the pituitary TGF-β1 system more strongly in females than in males, (2) males express higher levels of pituitary TGF-β1 system components including active cytokine, and (3) estradiol negatively controls most of the components of the system. Because TGF-β1 inhibits lactotroph proliferation, we propose that the higher levels of the TGF-β1 system in males could protect or delay the development of prolactinomas in Drd2-/- male mice. Copyright © 2013 by The Endocrine Society. |
| title |
Sex differences in the pituitary transforming growth factor-β1 system: Studies in a model of resistant prolactinomas |
| title_short |
Sex differences in the pituitary transforming growth factor-β1 system: Studies in a model of resistant prolactinomas |
| title_full |
Sex differences in the pituitary transforming growth factor-β1 system: Studies in a model of resistant prolactinomas |
| title_fullStr |
Sex differences in the pituitary transforming growth factor-β1 system: Studies in a model of resistant prolactinomas |
| title_full_unstemmed |
Sex differences in the pituitary transforming growth factor-β1 system: Studies in a model of resistant prolactinomas |
| title_sort |
sex differences in the pituitary transforming growth factor-β1 system: studies in a model of resistant prolactinomas |
| publishDate |
2013 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00137227_v154_n11_p4192_Recouvreux http://hdl.handle.net/20.500.12110/paper_00137227_v154_n11_p4192_Recouvreux |
| _version_ |
1768544984916557824 |