Non-pituitary GH regulation of the tissue microenvironment

Abstract

Non-pituitary GH (npGH) expression is well established in extrapituitary tissues, but understanding of the physiological role of npGH remains rather limited. Pro-tumorigenic npGH impacting the tumor microenvironment has been reviewed, and we focus here on autocrine/paracrine npGH effects in non-tumorous tissues and discuss its mechanisms of action in the normal tissue microenvironment. We address tissue-specific effects of npGH in regulating stem, endothelial, immune, and epithelial cells and highlight the related role of npGH-associated changes in tissue aging.

Hormones and Signaling Pathways Involved in the Stimulation of Leydig Cell Steroidogenesis

“…GH is a crucial peptide hormone that regulates several essential physiological processes in the body. It is primarily secreted by somatotrope cells located in the anterior pituitary, but local production of GH by many tissues has also been reported (reviewed in [75]). GH mediates its effects by binding to the GH-receptor (GHR) and, in some species, including humans, to the prolactin receptor (PRLR) [76,77] (reviewed in [78]).…”

WIP1 is a novel specific target for growth hormone action

“… 13 , 14 GH induces cell proliferation, 15 , 16 promotes epithelial-mesenchymal transition, 15 , 16 , 17 , 18 , 19 and suppresses DDR, leading to accumulated DNA damage, thus enabling a pre-neoplastic microenvironment. 16 , 17 , 20 , 21 , 22 GH and IGF1 have been implicated in breast, prostate, and colon neoplastic development. 21 , 23 , 24 Thus, acromegaly patients with excess GH secretion from a pituitary adenoma exhibit increased soft tissue tumors, colon polyps, and possibly adenocarcinomas 25 , 26 , 27 ; by contrast, inherited GH signaling deficiency impedes development of malignancy in humans with Laron syndrome and also in GH-signaling-deficient mice.…”