De Paul Ana Lucía, Gutiérrez Silvina, Sabatino María E, Mukdsi Jorge H, Palmeri Claudia M, Soaje Marta, Petiti Juan P, Torres Alicia I
Universidad Nac de Córdoba, Argentina.
Exp Physiol. 2011 Feb;96(2):226-39. doi: 10.1113/expphysiol.2010.054502.
Lactotroph cells display morphological and functional heterogeneity, a feature which is closely related to the oestrogenic environment. In this study, we focused on sex-related differences linked to the proliferative and secretory responses of lactotrophs exposed to EGF in vitro. Furthermore, we addressed the involvement of the PKCε/ERK1/2 signalling pathway and the contribution of Pit-1 in the EGF actions in primary pituitary cultures from male and female rats. EGF promoted a differential proliferative activity on PRL cells, which was closely associated to the sex, as revealed by the uptake of bromodeoxyuridine (BrdU). In females, the mitogenic activity was up to nine times greater, whereas in males, the number of BrdU-labelled PRL cells was only doubled compared to control. However, in both models, EGF had a similar effectiveness in promoting PRL secretion. EGF also induced a significant increase in the PKCε, P -ERK 1/2, and Pit-1 protein levels, which were higher in females than in males. Pre-incubation with BIM blocked EGF-induced ERK 1/2 activation and Pit-1 expression. These results suggest a sexually dimorphic response of lactotroph cells to the proliferative effects of EGF, with the PKCε/ERK1/2 Pit-1 pathway being involved in this action.
催乳素细胞表现出形态和功能的异质性，这一特征与雌激素环境密切相关。在本研究中，我们聚焦于与体外暴露于表皮生长因子（EGF）的催乳素细胞增殖和分泌反应相关的性别差异。此外，我们探讨了蛋白激酶Cε（PKCε）/细胞外信号调节激酶1/2（ERK1/2）信号通路的参与情况以及垂体特异性转录因子1（Pit-1）在雄性和雌性大鼠原代垂体培养物中EGF作用的贡献。通过溴脱氧尿苷（BrdU）摄取显示，EGF对催乳素（PRL）细胞具有不同的增殖活性，这与性别密切相关。在雌性中，促有丝分裂活性高达9倍，而在雄性中，与对照组相比，BrdU标记的PRL细胞数量仅增加了一倍。然而，在两种模型中，EGF在促进PRL分泌方面具有相似的效果。EGF还诱导PKCε、磷酸化ERK 1/2和Pit-1蛋白水平显著增加，雌性中的水平高于雄性。用BIM预孵育可阻断EGF诱导的ERK 1/2激活和Pit-1表达。这些结果表明催乳素细胞对EGF增殖作用存在性别二态性反应，PKCε/ERK1/2 Pit-1信号通路参与了这一作用。
