GH in the Central Nervous System: Lessons from the Growth Hormone Receptor Knockout Mouse

Abstract

Various central nervous system (CNS) tissues express both growth hormone (GH) and its receptor (GHR), including those involved in memory and cognition. Studies show the presence of GHR in the pituitary, choroid plexus, hypothalamus, hippocampus, pituitary and the spinal cord during development and, to a lesser extent, in adults. This expression implies a role of GH signaling in growth, development and functionality of the CNS. While data on the function of GH in the CNS is sparse, several studies have been conducted using the GHR knockout (-/-) mouse in order to better understand this role. Abnormal growth hormone signaling in humans is the cause of various diseases that include Laron syndrome, GH deficiency and acromegaly. This article will review the research conducted using the GHR-/-mouse on the role of GH signaling in the CNS. Where possible, we will attempt to contextualize the animal data with respect to human disease.

MECHANISMS IN ENDOCRINOLOGY: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects?

“…Later, quantitative PCR and immune-histochemical studies confirmed a near ubiquitous expression of GHR throughout the brain of humans as well as rats and mice (reviewed in (253,254,255)). Particularly high expression levels of GHR was observed in the choroid plexus, pituitary, hippocampus, thalamus, and hypothalamus (256).…”

“…The apparent dichotomy in the patterns of GH action in affecting cognition and memory is reflected in the decreased brain size in bGH mice and increased brain size in GHA and GHRKO animals relative to total body weight although the rest of the body parts show a more proportionate variation (253). However, no difference in total cell number was reported in the embryonal central nervous system of GHRKO mice and its WT counterparts(262).…”

The Associations of GH and GHR Genes with Carcass Components in Indonesian Kampung and Broiler Chicken Cross

“…The chicken growth hormone is widely known as a major hormone that acts directly on chicken development and metabolism (Kim, 2010) and relates to egg production (Su et al, 2014;Vu & Ngu, 2016). GH regulates a variety of physiological functions such as growth, body composition, egg production, aging, reproduction, sexual maturation, and functionality of the central nervous system (Gosney et al, 2012;Hrabia et al, 2008;Hull & Harvey, 2014;Stephen et al, 2001). The GH/ IGF-1 signaling pathway is also believed to be capable of promoting growth of selected types of cancer (Kopchick et al, 2014).…”

Intranasal Human Growth Hormone (hGH) Induces IGF-1 Levels Comparable With Subcutaneous Injection With Lower Systemic Exposure to hGH in Healthy Volunteers

“…This resulted in the development of a dry powder nasal formulation of hGH (CP024) ( 23 ). A variety of species has been shown to express GH and GH receptors in multiple tissues in the central nervous system such as the thalamus, hypothalamus, pituitary, and hippocampus, which implicates a role for GH signaling in the development and maintenance of neural tissue as well as cognition and memory ( 24 ) Furthermore, the regulation of GH synthesis and secretion is complex and involves modulation by both central and peripherally derived modulators ( 25 ) We hypothesized that the proximity of the pituitary gland and its blood supply to the site of absorption, the potential for direct nose to brain delivery of hGH with the possibly of reaching hGH receptors in the brain, and the potential for a more physiologically equivalent hGH plasma profile ( 26 , 27 ) could make the nasal route of delivery particularly promising for GH replacement therapy. After the completion of a preclinical safety assessment package on both CriticalSorb and CP024, the current studies evaluated the safety and tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of CP024 in healthy volunteers.…”