Non-classical Signalling of Growth Hormone in the Chick Neural Retina?

Abstract

Growth hormone (GH) signalling is traditionally via a 'classical' GH-receptor (GHR) that is present in the plasma membrane of target cells. GHRs are present in the neural retina of early chick embryos (within the first trimester of incubation) but these are unlikely to be endocrine target sites of GH action, as pituitary GH is not secreted into the bloodstream until late in development (approximately day 17 of the 21 days incubation period) and because the blood-ocular barrier would block the entry of systemic GH into the retina. As GH is expressed in the early neural retina, retinal GHRs are thus likely to be autocrine or paracrine sites of GH action. The most abundant GH moieties in the neural retina are, however, unlikely to activate 'classical' GHRs in the neural retina, as they are submonomeric molecules (of 15 kDa and 16.5 kDa) that fail to bind to plasma membrane receptor (15 kDa GH) or lack the stoichiometric requirements likely required for GHR binding (16.5 kDa GH). Nevertheless, 15 kDa GH is biologically active in chicks and the immunoneutralisation of endogenous 16.5 kDa GH induces biological activity. It is therefore possible that GH in the neural retina of early chick embryos acts non-classically or via 'non-classical' GHRs. These possibilities are the focus of this brief review.

Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors—a review of research and clinical practice

“…Moreover, a model to explain neoplastic colon growth has been proposed in which high endocrine or autocrine GH levels -for instance, as a result of acromegaly or colonic DNA damage and inflammation -inactivate tumor-suppressor genes, suppress apoptosis, and stimulates epithelial to mesenchymal transition, leading to changes in the intestinal mucosal field that favor malignant transformation [52]. Consequently, several components of the GH-IGF-I signaling cascades have been investigated as targets for the treatment of breast and colonic cancer, as well as for several other malignancies [53][54][55][56].…”