| First Author | Recouvreux MV | Year | 2013 |
| Journal | Endocrinology | Volume | 154 |
| Issue | 11 | Pages | 4192-205 |
| PubMed ID | 24008346 | Mgi Jnum | J:203821 |
| Mgi Id | MGI:5528780 | Doi | 10.1210/en.2013-1433 |
| Citation | Recouvreux MV, et al. (2013) Sex differences in the pituitary transforming growth factor-beta1 system: studies in a model of resistant prolactinomas. Endocrinology 154(11):4192-205 |
| abstractText | 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-beta1 is a known inhibitor of lactotroph proliferation. TGF-beta1 is regulated by dopamine and estradiol, and it is usually down-regulated in prolactinoma experimental models. To understand the role of TGF-beta1 in the gender-specific development of prolactinomas in Drd2(-/-) mice, we compared the expression of different components of the pituitary TGF-beta1 system, including active cytokine content, latent TGF-beta-binding protein isoforms, and possible local TGF-beta1 activators, in males and females in this model. Furthermore, we evaluated the effects of dopamine and estradiol administration to elucidate their role in TGF-beta1 system regulation. The expression of active TGF-beta1, latent TGF-beta-binding protein isoforms, and several putative TGF-beta1 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-beta1 content, as reflected by the down-regulation of TGF-beta1 target genes. Estrogen and dopamine caused differential regulation of several components of the TGF-beta1 system. In particular, we found sex- and genotype- dependent regulation of active TGF-beta1 content and a similar expression pattern for 2 of the putative TGF-beta1 activators, thrombospondin-1 and kallikrein-1, suggesting that these proteins could mediate TGF-beta1 activation elicited by dopamine and estradiol. Our results indicate that (1) the loss of dopaminergic tone affects the pituitary TGF-beta1 system more strongly in females than in males, (2) males express higher levels of pituitary TGF-beta1 system components including active cytokine, and (3) estradiol negatively controls most of the components of the system. Because TGF-beta1 inhibits lactotroph proliferation, we propose that the higher levels of the TGF-beta1 system in males could protect or delay the development of prolactinomas in Drd2(-/-) male mice. |
