Follistatin 315

Key Benefits#

• Systemic myostatin inhibition for whole-body muscle growth
• Freely circulating — broader tissue distribution than FST-344
• Strong FSH-suppressive activity useful in certain hormonal protocols
• Potential for greater anabolic effect across multiple muscle groups simultaneously
• May be more relevant to reproductive endocrinology applications
• Studied in gene therapy approaches for muscular dystrophy

Mechanism of Action#

FST-315 lacks the C-terminal domain present in FST-344 that enables heparan sulfate binding. This makes it freely diffusible in circulation rather than cell-surface tethered. It binds myostatin and activin A systemically, suppressing their signaling throughout the body. The broader distribution means stronger systemic anabolic and FSH-suppressive effects compared to FST-344. In the pituitary, FST-315 is the dominant isoform regulating FSH via activin inhibition.

Dosing Protocols#

Side Effects#

• Systemic FSH suppression — significant concern for fertility
• Greater potential for off-target effects vs FST-344 due to systemic distribution
• Limited human safety data
• Potential cardiac hypertrophy with prolonged high-dose exposure

Contraindications#

Not FDA approved. Contraindicated in women of reproductive age seeking pregnancy. Not appropriate without medical oversight. Minimal human clinical data.

Storage#

Lyophilized powder: store at -20°C. Reconstituted: refrigerate at 2–8°C, use within 3–5 days.

1. 1.
   Bone Geometry Is Altered by Follistatin-Induced Muscle Growth in Young Adult Male Mice

   Chan ASM, McGregor NE, Poulton IJ, Hardee JP, Cho EH, Martin TJ et al. · JBMR plus · 2021PubMed Verified

2. 2.
   Detection of black market follistatin 344

   Reichel C, Gmeiner G, Thevis M · Drug testing and analysis · 2019PubMed Verified

3. 3.
   Follistatin Effects in Migration, Vascularization, and Osteogenesis in vitro and Bone Repair in vivo

   Fahmy-Garcia S, Farrell E, Witte-Bouma J, Robbesom-van den Berge I, Suarez M, Mumcuoglu D et al. · Frontiers in bioengineering and biotechnology · 2019PubMed Verified

4. 4.
   Age-dependent cardiac function during experimental sepsis: effect of pharmacological activation of AMP-activated protein kinase by AICAR

   Inata Y, Piraino G, Hake PW, O'Connor M, Lahni P, Wolfe V et al. · American journal of physiology. Heart and circulatory physiology · 2018PubMed Verified

5. 5.
   Effect of follistatin on pre-implantational development of pig parthenogenetic embryos

   Li Y, Liu X, Chen Z, Song D, Yang J, Zuo X et al. · Animal science journal = Nihon chikusan Gakkaiho · 2018PubMed Verified

6. 6.
   Activin B Induces Noncanonical SMAD1/5/8 Signaling via BMP Type I Receptors in Hepatocytes: Evidence for a Role in Hepcidin Induction by Inflammation in Male Mice

   Canali S, Core AB, Zumbrennen-Bullough KB, Merkulova M, Wang CY, Schneyer AL et al. · Endocrinology · 2016PubMed Verified

7. 7.
   Characterization of secretomes provides evidence for adipose-derived mesenchymal stromal cells subtypes

   Kalinina N, Kharlampieva D, Loguinova M, Butenko I, Pobeguts O, Efimenko A et al. · Stem cell research & therapy · 2015PubMed Verified

8. 8.
   Insights into the Impact of Heterogeneous Glycosylation on the Pharmacokinetic Behavior of Follistatin-Fc-Based Biotherapeutics

   Datta-Mannan A, Huang L, Pereira J, Yaden B, Korytko A, Croy JE · Drug metabolism and disposition: the biological fate of chemicals · 2015PubMed Verified

9. 9.
   Follistatin is essential for normal postnatal development and function of mouse oviduct and uterus

   Holdsworth-Carson SJ, Craythorn RG, Winnall WR, Dhaliwal K, Genovese R, Nowell CJ et al. · Reproduction, fertility, and development · 2015PubMed Verified

10. 10.
    Increased activin bioavailability enhances hepatic insulin sensitivity while inducing hepatic steatosis in male mice

    Ungerleider NA, Bonomi LM, Brown ML, Schneyer AL · Endocrinology · 2013PubMed Verified

11. 11.
    An engineered human follistatin variant: insights into the pharmacokinetic and pharmocodynamic relationships of a novel molecule with broad therapeutic potential

    Datta-Mannan A, Yaden B, Krishnan V, Jones BE, Croy JE · The Journal of pharmacology and experimental therapeutics · 2013PubMed Verified

12. 12.
    The effects of transforming growth factor-β2 on the expression of follistatin and activin A in normal and glaucomatous human trabecular meshwork cells and tissues

    Fitzgerald AM, Benz C, Clark AF, Wordinger RJ · Investigative ophthalmology & visual science · 2012PubMed Verified

13. 13.
    Development of a second generation Inhibin B ELISA

    Kalra B, Kumar A, Patel K, Patel A, Khosravi MJ · Journal of immunological methods · 2010PubMed Verified

14. 14.
    Expression of myostatin and follistatin in Mdx mice, an animal model for muscular dystrophy

    Abe S, Soejima M, Iwanuma O, Saka H, Matsunaga S, Sakiyama K et al. · Zoological science · 2009PubMed Verified

15. 15.
    Expression of genes related to myostatin signaling during rat skeletal muscle longitudinal growth

    Aoki MS, Soares AG, Miyabara EH, Baptista IL, Moriscot AS · Muscle & nerve · 2009PubMed Verified

16. 16.
    Inhibition of myostatin with emphasis on follistatin as a therapy for muscle disease

    Rodino-Klapac LR, Haidet AM, Kota J, Handy C, Kaspar BK, Mendell JR · Muscle & nerve · 2009ReviewPubMed Verified

17. 17.
    Peroxisome proliferator-activated receptor gamma down-regulates follistatin in intestinal epithelial cells through SP1

    Necela BM, Su W, Thompson EA · The Journal of biological chemistry · 2008PubMed Verified

18. 18.
    A molecular recognition paradigm: promiscuity associated with the ligand-receptor interactions of the activin members of the TGF-beta superfamily

    Keah HH, Hearn MT · Journal of molecular recognition : JMR · 2005ReviewPubMed Verified

19. 19.
    Possible endocrine control by follistatin 315 during liver regeneration based on changes in the activin receptor after a partial hepatectomy in rats

    Takamura K, Tsuchida K, Miyake H, Tashiro S, Sugino H · Hepato-gastroenterology · 2005PubMed Verified

20. 20.
    Regulation of ovarian function by the TGF-beta superfamily and follistatin

    Lin SY, Morrison JR, Phillips DJ, de Kretser DM · Reproduction (Cambridge, England) · 2003ReviewPubMed Verified

21. 21.
    Dynamics of inhibin subunit and follistatin mRNA during development of normal and polycystic ovary syndrome follicles

    Fujiwara T, Sidis Y, Welt C, Lambert-Messerlian G, Fox J, Taylor A et al. · The Journal of clinical endocrinology and metabolism · 2001Clinical TrialPubMed Verified

22. 22.
    Follistatin production by skin fibroblasts and its regulation by dexamethasone

    Kawakami S, Fujii Y, Winters SJ · Molecular and cellular endocrinology · 2001PubMed Verified

23. 23.
    Difference between follistatin isoforms in the inhibition of activin signalling: activin neutralizing activity of follistatin isoforms is dependent on their affinity for activin

    Hashimoto O, Kawasaki N, Tsuchida K, Shimasaki S, Hayakawa T, Sugino H · Cellular signalling · 2000PubMed Verified

24. 24.
    Expression of inhibin betaA, betaB and follistatin mRNAs in the carbon tetrachloride induced rat liver regeneration model

    Kobayashi T, Niimi S, Hashimoto O, Hayakawa T · Biological & pharmaceutical bulletin · 2000PubMed Verified

25. 25.
    Molecular characterization of Xenopus embryo heparan sulfate. Differential structural requirements for the specific binding to basic fibroblast growth factor and follistatin

    Yamane Y, Tohno-oka R, Yamada S, Furuya S, Shiokawa K, Hirabayashi Y et al. · The Journal of biological chemistry · 1998PubMed Verified

26. 26.
    Development, validation and application of an ultra-sensitive two-site enzyme immunoassay for human follistatin

    Evans LW, Muttukrishna S, Groome NP · The Journal of endocrinology · 1998PubMed Verified

27. 27.
    A two-site chemiluminescent assay for activin-free follistatin reveals that most follistatin circulating in men and normal cycling women is in an activin-bound state

    McConnell DS, Wang Q, Sluss PM, Bolf N, Khoury RH, Schneyer AL et al. · The Journal of clinical endocrinology and metabolism · 1998ReviewPubMed Verified

28. 28.
    Presence of activin, inhibin, and follistatin in epithelial ovarian carcinoma

    Welt CK, Lambert-Messerlian G, Zheng W, Crowley WF Jr, Schneyer AL · The Journal of clinical endocrinology and metabolism · 1997PubMed Verified

29. 29.
    Follistatin and its role as an activin-binding protein

    Sugino H, Sugino K, Hashimoto O, Shoji H, Nakamura T · The journal of medical investigation : JMI · 1997ReviewPubMed Verified

30. 30.
    Expression of follistatin and inhibin/activin subunit genes in porcine follicles

    Li MD, DePaolo LV, Ford JJ · Biology of reproduction · 1997PubMed Verified

31. 31.
    A novel role of follistatin, an activin-binding protein, in the inhibition of activin action in rat pituitary cells. Endocytotic degradation of activin and its acceleration by follistatin associated with cell-surface heparan sulfate

    Hashimoto O, Nakamura T, Shoji H, Shimasaki S, Hayashi Y, Sugino H · The Journal of biological chemistry · 1997PubMed Verified

32. 32.
    The heparin binding site of follistatin is involved in its interaction with activin

    Sumitomo S, Inouye S, Liu XJ, Ling N, Shimasaki S · Biochemical and biophysical research communications · 1995PubMed Verified

33. 33.
    Effect of streptozotocin injection on expression of immunoreactive follistatin and beta A and beta B subunits of inhibin/activin in rat pancreatic islets

    Ogawa K, Ono K, Kurohmaru M, Hayashi Y · European journal of endocrinology · 1995PubMed Verified

34. 34.
    Isolation and characterization of bovine follistatin cDNA

    Saleh M, Garcia S, Mercer JE, Findlay JK · Journal of molecular endocrinology · 1994PubMed Verified

35. 35.
    Changes in the immunoreactivity of follistatin within preovulatory follicles after the primary gonadotrophin surge in rats

    Ogawa K, Kurohmaru M, Sugino H, Hayashi Y · Journal of reproduction and fertility · 1994PubMed Verified

36. 36.
    Molecular heterogeneity of follistatin, an activin-binding protein. Higher affinity of the carboxyl-terminal truncated forms for heparan sulfate proteoglycans on the ovarian granulosa cell

    Sugino K, Kurosawa N, Nakamura T, Takio K, Shimasaki S, Ling N et al. · The Journal of biological chemistry · 1993PubMed Verified

37. 37.
    Site-specific mutagenesis of human follistatin

    Inouye S, Guo Y, Ling N, Shimasaki S · Biochemical and biophysical research communications · 1991PubMed Verified

38. 38.
    Recombinant expression of human follistatin with 315 and 288 amino acids: chemical and biological comparison with native porcine follistatin

    Inouye S, Guo Y, DePaolo L, Shimonaka M, Ling N, Shimasaki S · Endocrinology · 1991PubMed Verified

39. 39.
    Characterization of antisera directed against follistatin/activin-binding protein peptides

    Saito S, Sugino K, Yamanouchi K, Kogawa K, Titani K, Shiota K et al. · Endocrinologia japonica · 1991PubMed Verified

40. 40.
    Structural characterization of follistatin: a novel follicle-stimulating hormone release-inhibiting polypeptide from the gonad

    Esch FS, Shimasaki S, Mercado M, Cooksey K, Ling N, Ying S et al. · Molecular endocrinology (Baltimore, Md.) · 1987PubMed Verified