Skinner M K, Coffey R J
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
Endocrinology. 1988 Dec;123(6):2632-8. doi: 10.1210/endo-123-6-2632.
The rapid proliferation of a tissue often requires the local production of a specific growth factor. The ovarian follicle is a rapidly growing tissue which contains two primary somatic cell types, granulosa cells and theca cells. Theca cells and granulosa cells were isolated from bovine ovaries and cultured to assess the possible local production of a growth factor within the ovarian follicle. Serum-free conditioned medium from theca cells, but not from granulosa cells, was found to contain a component that specifically bound to the epidermal growth factor (EGF) receptor. Therefore, theca cells appear to produce an EGF-like substance as a potential regulator of follicle cell growth. This result provides physiological significance to the previous observation that granulosa cells contain EGF receptors and respond to EGF to increase cell proliferation. Transforming growth factor-alpha (TGF alpha) is a protein that is structurally and functionally related to EGF and binds to the EGF receptor. Using a molecular probe to TGF alpha, theca cells were found to express the TGF alpha gene, which is consistent with the presence of an EGF-like substance in conditioned medium, but granulosa cells had no detectable TGF alpha gene expression. Similar analysis with a molecular probe to EGF demonstrated the apparent lack of EGF gene expression in theca cells or granulosa cells. As previously demonstrated with granulosa cells, the data presented indicate that theca cells also contain high affinity EGF receptors. TGF alpha was found to stimulate the growth of both granulosa and theca cells. These observations imply that within the ovarian follicle TGF alpha is produced by theca cells, which can subsequently have both a paracrine and an autocrine role in regulating follicle cell proliferation. Results presented demonstrate production of TGF alpha by a normal adult mesenchymal tissue and provide an example of a growth factor-mediated mesenchymal-epithelial cell interaction between theca cells and granulosa cells.
组织的快速增殖通常需要局部产生特定的生长因子。卵巢卵泡是一种快速生长的组织，其中包含两种主要的体细胞类型，即颗粒细胞和卵泡膜细胞。从牛卵巢中分离出卵泡膜细胞和颗粒细胞并进行培养，以评估卵巢卵泡内是否可能局部产生生长因子。发现卵泡膜细胞的无血清条件培养基中含有一种能与表皮生长因子（EGF）受体特异性结合的成分，而颗粒细胞的无血清条件培养基中则没有。因此，卵泡膜细胞似乎产生一种类表皮生长因子物质，作为卵泡细胞生长的潜在调节因子。这一结果为先前的观察提供了生理学意义，即颗粒细胞含有EGF受体并对EGF作出反应以增加细胞增殖。转化生长因子-α（TGFα）是一种在结构和功能上与EGF相关且能与EGF受体结合的蛋白质。使用针对TGFα的分子探针，发现卵泡膜细胞表达TGFα基因，这与条件培养基中存在类表皮生长因子物质一致，但颗粒细胞未检测到TGFα基因表达。用针对EGF的分子探针进行的类似分析表明，卵泡膜细胞或颗粒细胞中明显缺乏EGF基因表达。如先前在颗粒细胞中所证明的那样，所呈现的数据表明卵泡膜细胞也含有高亲和力的EGF受体。发现TGFα能刺激颗粒细胞和卵泡膜细胞的生长。这些观察结果表明，在卵巢卵泡内，TGFα由卵泡膜细胞产生，随后在调节卵泡细胞增殖中可发挥旁分泌和自分泌作用。所呈现的结果证明了正常成年间充质组织产生TGFα，并提供了一个生长因子介导的卵泡膜细胞与颗粒细胞之间的间充质 - 上皮细胞相互作用的例子。
