González-Parra S, Chowen J A, Garciá Segura L M, Argente J
Universidad Autónoma, Hospital Infantil Niño Jesús, Madrid, Spain.
J Neuroendocrinol. 1996 Mar;8(3):211-25. doi: 10.1046/j.1365-2826.1996.04526.x.
Pituitary transcription factor-1 (Pit-1 or GHF-1), a transcription factor specific to the anterior pituitary, is involved in the expression and regulation of the growth hormone (GH) and prolactin (PRL) genes. Post-pubertally, the expression of both GH and PRL becomes sexually dimorphic with males having higher GH levels and females higher PRL levels; however, little is known about the postnatal regulation of their common transcription factor. Furthermore, whether the Pit-1 gene is differentially expressed in somatotrophs and lactotrophs remains to be elucidated. In this study, we used in situ hybridization histochemistry to examine Pit-1, GH and PRL mRNA levels in the anterior pituitaries of male and female rats throughout development (0, 5, 10, 20, 30, 40 and 60 days of age) to determine when GH and PRL production becomes sexually dimorphic and if this is accompanied by a dimorphism in Pit-1 gene expression. In addition, the level of Pit-1 mRNA was determined separately in both GH mRNA and PRL mRNA containing cells during the various developmental stages. We found that in both males and females the mRNA levels of Pit-1, GH and PRL remain relatively unchanged until around the time of pubertal onset (30-40 days) when there is a significant increase in all three mRNA species, which is followed by a decrease to adult levels. Also around the time of puberty, both GH and PRL mRNA levels become sexually dimorphic, with males having higher levels of GH mRNA and females higher PRL mRNA levels. In contrast, at no time during development were overall Pit-1 mRNA levels found to differ between the sexes. However, when Pit-1 mRNA content was measured separately in specific cell types, significant differences between the sexes became evident. Throughout development Pit-1 mRNA levels are higher in lactotrophs of females than in those of males, whereas in somatotrophs males have higher Pit-1 mRNA levels than females. Furthermore, within a sex there is differential expression of Pit-1 in the two cell types with females having significantly higher levels of Pit-1 in lactotrophs than in somatotrophs and males having higher levels in somatotrophs than in lactotrophs. These data support the hypothesis that a sexual dimorphism exists in the expression and pituitary specific transcription factor Pit-1; however, this dimorphism is not manifest as a difference in overall mRNA levels, but in the differential expression of this gene in lactotrophs and somatotrophs.
垂体转录因子-1（Pit-1或GHF-1）是一种垂体前叶特异性转录因子，参与生长激素（GH）和催乳素（PRL）基因的表达与调控。青春期后，GH和PRL的表达呈现出性别差异，雄性的GH水平较高，雌性的PRL水平较高；然而，关于它们共同转录因子的出生后调控却知之甚少。此外，Pit-1基因在生长激素细胞和催乳激素细胞中是否存在差异表达仍有待阐明。在本研究中，我们采用原位杂交组织化学技术检测了雄性和雌性大鼠在整个发育过程（0、5、10、20、30、40和60日龄）垂体前叶中Pit-1、GH和PRL的mRNA水平，以确定GH和PRL的产生何时出现性别差异，以及这是否伴随着Pit-1基因表达的性别差异。此外，在不同发育阶段，分别测定了含GH mRNA和PRL mRNA的细胞中Pit-1 mRNA的水平。我们发现，在雄性和雌性大鼠中，Pit-1、GH和PRL的mRNA水平在青春期开始（30 - 40天）之前相对保持不变，之后这三种mRNA水平均显著升高，随后又降至成年水平。同样在青春期前后，GH和PRL的mRNA水平出现性别差异，雄性的GH mRNA水平较高，雌性的PRL mRNA水平较高。相比之下，在整个发育过程中，未发现两性之间Pit-1的总体mRNA水平存在差异。然而，当分别在特定细胞类型中测量Pit-1 mRNA含量时，两性之间的显著差异就变得明显了。在整个发育过程中，雌性催乳激素细胞中的Pit-1 mRNA水平高于雄性，而在生长激素细胞中，雄性的Pit-1 mRNA水平高于雌性。此外，在同一性别中，Pit-1在这两种细胞类型中的表达也存在差异，雌性催乳激素细胞中的Pit-1水平显著高于生长激素细胞，而雄性生长激素细胞中的Pit-1水平高于催乳激素细胞。这些数据支持了以下假设：垂体特异性转录因子Pit-1的表达存在性别差异；然而，这种差异并非表现为总体mRNA水平的差异，而是该基因在催乳激素细胞和生长激素细胞中的差异表达。
