Can you Increase Height by Inhibiting Activin?

Activin stimulates Follicle Stimulating Hormone which is involved in the menstrual cycle.  Mutations in activin receptor type I can induce heterotopic ossification.  So maybe changes in activin receptor type I in bone can be used to re-establish height growth.  GASP-1, which is upregulated by resisitance training, inhibits activin.  Activin Receptor Type II b is also required for myostatin inhibition of cellular differentiation.  Can you increase height by inhibiting activin?  Yes.  Activin seems to play a role in inhibiting cellular differentiation(and therefore chondrogenic differentiation) thus inhibiting height growth.  Of note is that LSJL does alter follistatin expression.

Overexpression of BMP3 in the developing skeleton alters endochondral bone formation resulting in spontaneous rib fractures. 

"Bone morphogenetic protein-3 (BMP) [is] a negative regulator in the skeleton as mice lacking BMP3 have increased bone mass[only bone density not increased stature]. We created transgenic mice overexpressing BMP3 using the type I collagen promoter. BMP3 transgenic mice displayed spontaneous rib fractures that were first detected at E17.0. The fractures were due to defects in differentiation of the periosteum and late hypertrophic chondrocytes resulting in thinner cortical bone with decreased mineralization. As BMP3 modulates BMP and activin signaling through ActRIIB, we examined the ribs of ActRIIB receptor knockout mice and found they had defects in late chondrogenesis and mineralization similar to BMP3 transgenic mice. BMP3 exerts its effects in the skeleton by altering signaling through ActRIIB in chondrocytes and the periosteum[LSJL proceeds through ACTRII signaling whether it's A or B is not specified], and this results in defects in bone collar formation and late hypertrophic chondrocyte maturation leading to decreased mineralization and less bone." 

"BMP ligands selectively use the type I receptors Alk2, Alk3, and Alk6 and the type II receptor, BMPR-II while sharing the other type II receptors, ActRIIA and ActRIIB with activin-like ligands. Upon BMP binding, type II receptors phosphorylate type I receptors. The activated type I receptor subsequently phosphorylates receptor regulated Smads (R-Smads 1, 5, 8) that then bind to Smad4"

"BMPs are required at the earliest stages of skeletogenesis for mesenchymal cell compaction and condensation and to maintain Sox9 expression in the embryonic limb"

"BMP signaling is regulated by ligand antagonists such as noggin, chordin, or gremlin that bind to BMPs and prevent them from interacting with their receptors, and by receptor antagonists like inhibin and BMP3 that bind to type II receptors preventing BMP proteins from initiating signal transduction on target cells"

"At all stages analyzed in long bone and rib, BMP3 was not detected in chondrocytes"<-BMP-3 transgenic mice had normal stature. So not all BMPs affect height. And maybe the modifications of Activin receptors are not such that would affect height.

Activins and follistatins: Emerging roles in liver physiology and cancer. 

"Activins are secreted proteins belonging to the TGF-β family of signaling molecules. Activin signals are crucial for differentiation and regulation of cell proliferation and apoptosis in multiple tissues. Signal transduction by activins relies mainly on the Smad pathway, although the importance of crosstalk with additional pathways is increasingly being recognized. Activin signals are kept in balance by antagonists at multiple levels of the signaling cascade. Among these, follistatin and FLRG,[follistatin inhibits activin] two members of the emerging family of follistatin-like proteins, can bind secreted activins with high affinity, thereby blocking their access to cell surface-anchored activin receptors. The functions of other activins expressed by hepatocytes have yet to be more clearly defined. Deregulated expression of activins and follistatin has been implicated in hepatic diseases including inflammation, fibrosis, liver failure and primary cancer. In particular, increased follistatin levels have been found in the circulation and in the tumor tissue of patients suffering from hepatocellular carcinoma as well as in animal models of liver cancer. Up-regulation of follistatin protects neoplastic hepatocytes from activin-mediated growth inhibition and apoptosis." 

Now remember that just because follistatin levels are upregulated in cancer doesn't mean that follistatin is the cause of cancer.  Genetic mutation is the cause of cancer.  Follistatin is a potent inhibitor of activin and myostatin.  As would be expected exercise increases Follistatin levels... 

Exercise induces a marked increase in plasma follistatin: evidence that follistatin is a contraction-induced hepatokine. 

"Follistatin is a member of the TGF-β super family and inhibits the action of myostatin[and activin] to regulate skeletal muscle growth. The regulation of follistatin during physical exercise is unclear but may be important because physical activity is a major intervention to prevent age-related sarcopenia. First, healthy subjects performed either bicycle or one-legged knee extensor exercise. Arterial-venous differences were assessed during the one-legged knee extensor experiment. Next, mice performed 1 h of swimming, and the expression of follistatin was examined in various tissues using quantitative PCR. Western blotting assessed follistatin protein content in the liver. IL-6 and epinephrine were investigated as drivers of follistatin secretion. After 3 h of bicycle exercise, plasma follistatin increased 3 h into recovery with a peak of 7-fold. No net release of follistatin could be detected from the exercising limb. In mice performing a bout of swimming exercise, increases in plasma follistatin as well as follistatin mRNA and protein expression in the liver were observed. IL-6 infusion to healthy young men did not affect the follistatin concentration in the circulation. When mice were stimulated with epinephrine, no increase in the hepatic mRNA of follistatin was observed. This is the first study to demonstrate that plasma follistatin is increased during exercise and most likely originates from the liver. These data introduce new perspectives regarding muscle-liver cross talk during exercise and during recovery from exercise." 

One more reason to do exercise and other forms of lifting while performing LSJL. 

"Follistatin possesses the ability to suppress secretion of FSH"

"Skeletal muscle releases IL-6 into the circulation during exercise[IL-6 may be anabolic to bone growth, thus more IL-6 in the system may be height promoting], and we have previously shown that IL-6 acts as a myokine, signaling from the muscle to the liver to increase liver glucose production during exercise. In the current study, plasma IL-6 peaked before the increase in plasma follistatin (IL-6 peaks after 3 h rising from 0.3 pg/ml to 12.2 pg/ml"

Activin(especially ActRIIb) decreases height growth by inhibiting cellular differentiation.  Therefore you can grow taller by increasing plasma levels of follistatin which inhibits activin.  The safest and most effective way to do that is exercise.

TGFbeta/Activin/Nodal pathway in inhibition of human embryonic stem cell differentiation by mechanical strain.

"Cyclic biaxial mechanical strain has been reported to inhibit human embryonic stem cell differentiation without selecting against survival of differentiated or undifferentiated cells[LSJL induces strain]. We show that TGFbeta/Activin/Nodal signaling plays a crucial role in repression of human embryonic stem cell (hESC) differentiation under mechanical strain[the LSJL studies actually had very low microstrain, so maybe the key is to have such a low strain as to note activate repression signaling but still induce hydrostatic pressure based chondrogenic differentiation]. Strain-induced transcription of TGFbeta1, Activin A, and Nodal, and upregulated Similar to Mothers Against Decapentaplegic homolog (Smad)2/3 phosphorylation in undifferentiated hESC. TGFbeta/Activin/Nodal receptor inhibitor SB431542 stimulated differentiation of hESCs cultured under biaxial strain. Exogenous addition of TGFbeta1, Activin A{LSJL downregulates an Activin receptor Acvrl1}, or Nodal alone was insufficient to stimulate hESC self-renewal to replicate behavior of hESCs in presence of strain. However, exogenous TGFbeta1 and Activin A in combination partially replicated the self-renewing phenotype induced by strain but when combined with strain did not further stimulate self-renewal[so the stem cells proliferated which is anabolic]. In presence of mechanical strain, addition of a neutralizing antibody to TGFbeta1 promoted hESC differentiation whereas inhibition of Activin A by Follistatin promoted hESC differentiation to a lesser extent[inhibiting of Activin A by Follistatin could promote MSC differentiation as well]. Together, these findings show that TGFbeta superfamily activation of Smad2/3 is required for repression of spontaneous differentiation under strain and suggest that strain may induce autocrine or paracrine signaling through TGFbeta superfamily ligands."

"Mechanical strain was not sufficient to inhibit differentiation"<-So differentiation can still occur under LSJL.

"The Smad1/5 branch transduces BMP and GDF ligand signals via the RIs Alk1, Alk2, Alk3, and Alk6. The TGFβ/Activin/Nodal branch activates Smad2/3 via Alk4, Alk5, and Alk7"

"Nodal and Activin share type I and II receptors and have the same Smad signaling pathway (Smad2/3), whereas TGFβ1 preferentially uses TGFβ1 receptors (Alk5, TβRII) and Smad2/3. After activation of the type I and type II receptor complexes, receptor Smads (Smad5/8 and Smad2/3) are phosphorylated."

"strain induced TGFβ1, Activin A, and Nodal expression as well as activated Smad2/3 phosphorylation."

"bFGF has been reported to act as a competence factor for TGFβ/Activin/Nodal signaling because its positive effect on pluripotency strictly depends on TGFβ/Activin/Nodal signaling"