Insulin-Like growth factor-I mRNA and peptide in the human anterior pituitary

Abstract

The pituitary is the central organ regulating virtually all endocrine processes, and pathologies of the pituitary cause manifold adverse effects. Because insulin-like growth factor (IGF)-I appears to be involved in tumour pathogenesis, progression, and persistence, and only few data exist on the cellular synthesis sites of IGF-I, the present study aims to create a basis for further research on pituitary adenomas by investigating the presence of IGF-I in the human pituitary using reverse transcriptase-polymerase chain reaction, in situ hybridisation, immunohistochemistry and immunocytochemistry. IGF-I was expressed in the pituitary, and gene sequence analysis revealed a sequence identical to that found in human liver. The distribution pattern of IGF-I mRNA found by in situ hybridisation corresponded to that of IGF-I peptide in immunohistochemistry. In all pituitary samples investigated, IGF-I-immunoreactivity occurred in almost all adrenocorticotrophic hormone (ACTH)-immunoreactive cells. Occasionally, an interindividually varying number of growth hormone (GH) and, infrequently, follicle-stimulating hormone and luteinising hormone cells contained IGF-I-immunoreactivity but none was detected in supporting cells. At the ultrastructural level, IGF-I-immunoreactivity was confined to secretory granules in coexistence with ACTH- or GH-immunoreactivity, respectively, indicating a concomitant release of the hormones. Thus, in humans, IGF-I appears to be a constituent in ACTH cells whereas its production in GH-producing and gonadotrophic cells may depend on the physiological status (e.g. serum IGF-I level, age or reproductive phase). It is assumed that locally produced IGF-I plays a crucial role in the regulation of endocrine cells by autocrine/paracrine mechanisms in addition to the endocrine route.