Immunohistological localization of TGFα, EGF, IGF-I, and TGFβ in the normal human pituitary gland.

Abstract

In previous studies, we demonstrated several growth factors, including epidermal growth factor (EGF), transforming growth factorβ (TGFβ), insulin-like growth factor-I (IGF-I, somatomedin C), and TGFe in extracts of the human pituitary. Using immunohistochemistry, reactivity for TGFα, EGF, and TGFβ was localized in sections of 12 of 12 autopsy-derived human pituitary glands. IGF-I reactivity was demonstrated in 5 of 5 pituitary glands. Sections staining for TGFα and IGF-I were double-stained for the full spectrum of anterior pituitary hormones (i.e., GH, PRL, ACTH, LH, FSH, TSH, and a-subunit). Intracellular EGF immunostaining was demonstrated within the posterior pituitary and in some squamous cell nests of the pars tuberalis. Occasional extracellular EGF reactivity was also noted within connective tissue of the anterior pituitary. Polyclonal antibody to TGFβ showed extracellular reactivity within connective tissue surrounding the gland as well as that separating cords of secretory cells. TGFβ staining was also noted in the mediae of small vessels. Monoclonal anti-TGFα antibody labeled scattered secretory cells throughout the anterior pituitary, including ones engaged in follicle formation, and some cells lining Rathke's cleft remnants. TGFα reactivity in secretory cells was expressed in cells also staining for PRL, α-subunit, LH, FSH, and TSH. No TGFα reactivity was noticed in cells staining for either GH or ACTH. IGF-I reactivity was observed in occasional secretory cells within the anterior pituitary and in neuronal processes of the posterior pituitary. Anterior pituitary cells reactive for hormones were nonreactive for IGF-I. The presence of EGF and TGFβ reactivity within extracellular matrix suggests that it represents a possible storage site of these growth factors within the anterior pituitary. The presence of EGF and IGF-I within the axons and terminations of posterior pituitary implies either local or possibly hypothalamic production of EGF. Finally, our results indicate that TGFα and IGF-I, as well as perhaps EGF, are manufactured by specific pituitary cells and that they may have a role in the endocrine function of the anterior and posterior pituitary, respectively.