Lü F, Yang K, Han V K, Challis J R
Department of Obstetrics and Gynecology, University of Western Ontario, London, Canada.
J Mol Endocrinol. 1995 Jun;14(3):323-36. doi: 10.1677/jme.0.0140323.
Activation of the fetal pituitary-adrenal axis is crucial for fetal organ maturation and the onset of parturition in sheep. Many factors including corticotrophin-releasing hormone (CRH) and arginine vasopressin secreted from the hypothalamus, and growth factors produced within the pituitary may be involved in the regulation of maturation of the fetal pituitary gland. IGFs have mitogenic and differentiation-promoting capacities in a variety of organs and are synthesized as paracrine factors within developing tissues. However, there is little information concerning the synthesis, distribution, regulation and function of IGFs in the fetal pituitary gland at different times during pregnancy. Therefore, we have localized IGF-I and IGF-II mRNAs and peptides, and determined the effect of cortisol on the level of IGF-II mRNAs in the pituitary glands of developing sheep fetuses. We examined the possible effects of IGFs on corticotroph function in cultures of adenohypophysial cells from term fetuses. Seven species of IGF-II transcripts of 1.2-6.0 kb were identified by Northern blot analysis in the pituitary gland of fetuses between day 60 of gestation and term (day 145). The levels of IGF-II mRNAs did not change significantly during pregnancy, although there was a trend for the presence of higher levels of IGF-II mRNAs at day 60 of gestation. IGF-I mRNA was not detectable. By in situ hybridization, IGF-II mRNA was localized to non-endocrine cells and to cells lining the blood vessels of the pars distalis, to some presumed endocrine cells in the pars distalis and pars intermedia, and to clusters of cells in the pars nervosa. In contrast, IGF-I and IGF-II peptides were detected in the presumed endocrine cells in the pars distalis and pars intermedia but not in the pars nervosa. Incubation of adenohypophysial cells from term fetuses with IGF-I, but not IGF-II, for 48 h increased specific 125I-Tyr-ovine CRH binding. However, neither IGF-I nor IGF-II had any significant effects on the basal or CRH-stimulated immunoreactive (ir)-ACTH output, the level of POMC mRNA or the number of ir-ACTH positive cells. Infusion of cortisol to fetuses starting at day 96 of gestation for 100 h or at days 120-125 of gestation for 84 h did not affect the level of IGF-II mRNAs in the pars distalis but decreased the levels of POMC mRNA. These results are consistent with IGFs having the potential to influence fetal pituitary function, although probably on cell types other than the corticotrophs.(ABSTRACT TRUNCATED AT 400 WORDS)
胎儿垂体 - 肾上腺轴的激活对于绵羊胎儿器官成熟和分娩启动至关重要。许多因素包括下丘脑分泌的促肾上腺皮质激素释放激素(CRH)和精氨酸加压素,以及垂体内产生的生长因子,可能参与胎儿垂体成熟的调节。胰岛素样生长因子(IGFs)在多种器官中具有促有丝分裂和促进分化的能力,并作为旁分泌因子在发育中的组织内合成。然而,关于孕期不同阶段胎儿垂体中IGFs的合成、分布、调节和功能的信息很少。因此,我们定位了IGF - I和IGF - II的mRNA及肽,并确定了皮质醇对发育中绵羊胎儿垂体中IGF - II mRNA水平的影响。我们研究了IGFs对足月胎儿腺垂体细胞培养物中促肾上腺皮质激素细胞功能的可能影响。通过Northern印迹分析,在妊娠60天至足月(第145天)的胎儿垂体中鉴定出7种1.2 - 6.0 kb的IGF - II转录本。尽管在妊娠60天时存在IGF - II mRNA水平较高的趋势,但孕期IGF - II mRNA水平没有显著变化。未检测到IGF - I mRNA。通过原位杂交,IGF - II mRNA定位于远侧部的非内分泌细胞和血管内皮细胞、远侧部和中间部一些假定的内分泌细胞以及神经部的细胞簇。相反,在远侧部和中间部假定的内分泌细胞中检测到IGF - I和IGF - II肽,但在神经部未检测到。用IGF - I而非IGF - II孵育足月胎儿的腺垂体细胞达48小时,可增加特异性125I - Tyr - 羊CRH结合。然而,IGF - I和IGF - II对基础或CRH刺激的免疫反应性(ir)-促肾上腺皮质激素(ACTH)分泌、POMC mRNA水平或ir - ACTH阳性细胞数量均无显著影响。从妊娠96天开始对胎儿输注皮质醇100小时或在妊娠120 - 125天输注84小时,不影响远侧部IGF - II mRNA水平,但降低了POMC mRNA水平。这些结果表明IGFs有可能影响胎儿垂体功能,尽管可能作用于促肾上腺皮质激素细胞以外的细胞类型。(摘要截短至400字)