Short and tall stature: a new paradigm emerges.
Full Study->jeffreybaron study
“In the past, the growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis was often considered to be the main system that regulated childhood growth and, therefore, determined short stature and tall stature. However, findings have now revealed that the GH-IGF-1 axis is just one of many regulatory systems that control chondrogenesis in the growth plate, which is the biological process that drives height gain. Consequently, normal growth in children depends not only on GH and IGF-1 but also on multiple hormones, paracrine factors, extracellular matrix molecules and intracellular proteins that regulate the activity of growth plate chondrocytes. Mutations in the genes that encode many of these local proteins cause short stature or tall stature. Similarly, genome-wide association studies have revealed that the normal variation in height seems to be largely due to genes outside the GH-IGF-1 axis that affect growth at the growth plate through a wide variety of mechanisms. These findings point to a new conceptual framework for understanding short and tall stature that is centred not on two particular hormones but rather on the growth plate, which is the structure responsible for height gain.”
Note extracellular fluid is listed as a factor and extracellular fluid flow can be modified by LSJL.
“the vast majority of children with short stature do not have a well-substantiated defect in the GH–IGF-1 axis.”
“Many new genes have been identified that, when mutated, result in short stature or tall stature, the majority of which do not participate in the GH–IGF-1 system”
“Estrogen has complex effects on the growth plate, not only altering growth rate, but also accelerating the loss of progenitor cells in the resting zone and thereby speeding up the developmental program of growth plate senescence, which causes early cessation of growth”
“tumour necrosis factor, IL-1β and IL-6 act directly on growth plate cartilage to suppress bone growth”
“fairly low doses of ionizing radiation, such as a single dose of 10 Gy, can impair longitudinal growth. Mechanical compression across the growth plate also impairs the elongation of bones, which is partly due to decreased enlargement of hypertrophic chondrocytes.”<-Chondrocyte hypertrophy size increases due to lsjl.
“FGFR-3 signalling negatively regulates growth by decreasing proliferation in the proliferative zone, decreasing production of the extracellular matrix, accelerating the onset of hypertrophic differentiation and decreasing the size of the hypertrophic chondrocytes”
“~2% of children who present with idiopathic short stature have mutations in NPR2, Conversely, overexpression of CNP or activating mutations in NPR2 result in tall stature.”
” Binding of CNP to NPR2 stimulates the guanylyl cyclase activity of the receptor, thereby increasing synthesis of cGMP, which activates the type II cGMP-dependent protein kinase”
“Of individuals presenting with idiopathic short stature, 2–15% have mutations in SHOX, with the exact percentage depending on the study. Conversely, increased copies of SHOX are associated with tall stature in individuals with Klinefelter syndrome and other types of sex chromosome aneuploidy”
“Sotos syndrome (characterized by tall stature) is associated with decreased activity of the Ras–MAPK pathway.”
“Ras, a small GTPase, signals via MAPK cascades to phosphorylate numerous cytoplasmic and nuclear proteins, regulating cell proliferation and differentiation.”
“heterozygous mutations in DNA methyltransferase 3A (DNMT3A) cause tall stature, a distinctive facial appearance and intellectual disability.”
“heterozygous mutations in EZH2, which encodes an enzyme that specifically methylates lysine residue 27 of histone 3 (H3K27, which is associated with transcriptional repression), are associated with Weaver syndrome (characterized by prenatal and postnatal overgrowth and a markedly advanced bone age).”
There’s a lot more covered in the study than I mentioned here. The full study is worthwhile to read.