EPIDERMAL GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA MESSENGER RIBONUCLEIC-ACIDS AND THEIR RECEPTORS IN THE RAT ANTERIOR-PITUITARY - LOCALIZATION AND REGULATION

Evidence has shown that epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha) and their receptors (EGF receptors) are present in the anterior pituitary, indicating that the growth factors are synthesized in situ and act locally. Studies have demonstrated that EGF could stimulate the hypothalamus-pituitary-adrenal (HPA) cortex axis, particularly at the pituitary level in vivo and in vitro, and also stimulate TGF alpha messenger RNA (mRNA) expression in cultured bovine pituitary cells. Recently, our studies have demonstrated that some stresses up-regulated EGF mRNA expression in the anterior pituitary, as detected by ribonuclease protection assay, further indicating the possible roles of EGF in the stress response. However, little is yet known about the sources and targets (sites of EGF receptors) of the growth factors in the pituitary. Therefore, this study was designed to localize EGF and TGF alpha mRNA and their receptors as well as to assess the effects of cold stress (CS) on their expression in the subsets of pituitary cells. In situ hybridization immunocytochemistry coupled with immunocytochemistry and dual immunocytochemistry studies revealed the presence of 1) EGF mRNA in somatotropes and gonadotropes; 2) TGF alpha mRNA in somatotropes, gonadotropes, and lactotropes; and 3) EGF receptors in all subsets of pituitary cells. CS (30 min) induced the expression of EGF mRNA in corticotropes and thyrotropes. EGF expression was not altered in somatotropes and gonadotropes. No significant changes were detected in TGF alpha mRNA expression in the pituitary cells after 30 min of CS. Expression of EGF receptors was also increased after 30 min of CS. This resulted from increases in EGF receptor-labeled cells among thyrotropes and gonadotropes. The cold stress-induced expression of EGF mRNA in corticotropes and thyrotropes fits with their overall activation after this type of stress. The increase in EGF receptor-labeled cells among thyrotropes may point to an important autocrine role for EGF in maintaining TSH responses to cold. On the other hand, the significance of EGF receptor up-regulation in gonadotropes (FSH-containing cells) caused by CS remains unknown.