Follistin (follitropin beta)

From Proteopedia

Follitropin beta injection is used to treat infertility in both males and females. Brand names for follitropin beta include Follistim, Follistim AQ, and Gonal-F RFF. This hormone is man-made gonadotropin to replace a bodily hormone called Follicle Stimulating Hormone (FSH). In males, FSH controls the production of sperm and in females FSH controls the maturation of follicles and ultimately their ability to ovulate. FSH is produced by the pituitary gland. Some fertility programs such as Assisted Reproductive Technology (ART) use follitropin beta, in conjunction with human chorionic gonadotropin (hCG), to help oocytes develop in women. Follitropin beta is also used in men, along with hCG to increase sperm count.

Function and Clinical Use

FSH stimulates the growth and healthy function of ovarian follicles. FSH in males is involved in maintaining normal levels of sperm production. (Oxford source) The first step of follicle formation is determined by the concentration of FSH. A woman who is not producing enough FSH will not be able to meet the concentration threshold necessary to begin pre-ovulatory development. If pre-ovulatory development does not occur a mature egg will not be formed to be fertilized. In females, FSH is critical for the onset of follicular development and the number of follicles reaching maturity. Follistim is used to treat these infertility issues. Human chorionic gonadotropin (hCG) must be given after follitropin beta injections in order for ovulation to take place after follicular growth. Follistim is intended for use in women who are participating in Assisted Reproductive Technology (ART) in order for multiple follicular development. It is also used in women who are unable to ovulate due to functional issues and not failure of the ovary itself.

Side Effects

Possible side effects from this drug include abnormal ovarian enlargement, Ovarian Hyperstimulation Syndrome (OHSS), spontaneous abortion, severe abdominal/stomach pain, bloating and rapid weight gain, nausea, and vomiting. Less common side effects include heavy non-menstrual vaginal bleeding, unusual tiredness and/or weakness, increased heart rate, and swelling of the breasts.

Structure

The amino acid sequence and structure of follitropin beta are exactly the same as that of human urinary follicle-stimulating hormone (hFSH). Follitropin beta a glycoprotein hormone that is created through recombinant DNA technology. The dimeric structure of follitropin beta contains 2 glycoprotein subunits – alpha and beta. The alpha subunit is glycosylated at Asn 51 and Asn 78 while the beta subunit is glycosylated at Asn 7 and Asn 24.

Mechanism

Follitropin Beta is a form of follicular stimulating hormone (FSH), which acts through a G-protein receptor on the surface of cells. FSH binds the receptor, FSHR, on the target cell. FSH experiences a conformational change which then allow the sulfotyrosine (sTYS335) on the receptor to bind to the FSH. This activates the transmembrane domain. The activation of this domain causes the enzyme, kinase, to phosphorylate a serine and threonine on the C-terminal end of the receptor using ATP. The newly phosphorylated serine and threonine cause the activation of the signaling molecule PI3K. After PI3K is activated, it then activates the APK kinase cascade, leading to different cellular responses.

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References

References (We understand that these references are not correctly cited. Once in proteopedia, we will correct them).

Follitropin Beta (By injection) - National Library of Medicine - PubMed Health. Retrieved March 28, 2017, from   https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0010381/?report=details

Follistim® AQ Cartridge [physician insert]. Food and Drug Administration. Retrieved March 26, 2017, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021273lbl.pdf DrugBank (Ed.). Follitropin beta. In DrugBank. Retrieved March 27, 2017, from https://www.drugbank.ca/drugs/DB00066 http://www.rcsb.org/pdb/explore/literature.do?structureId=1XWD - THE ONLY ONE THAT NEEDS TO BE DONE https://www.drugbank.ca/drugs/DB00066 http://www.merck.com/product/usa/pi_circulars/f/follistim_aq_cartridge/follistim_cartridge_pi.pdf https://www.drugs.com/sfx/follistim-aq-side-effects.html

Hillier, S. G. (1994). Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis. Human Reproduction, 9(2), 188–191. https://doi.org/10.1093/oxfordjournals.humrep.a138480

DrugBank (Ed.). (2017, April 17). Follitropin beta. In DrugBank. Retrieved from https://www.drugbank.ca/drugs/DB00066

Drug Approval Package: Follistim AQ (Follitropin) NDA #021273. (n.d.). Retrieved April 18, 2017, from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/021273s000TOC.cfm

Follistim AQ Side Effects in Detail. (n.d.). Retrieved April 18, 2017, from https://www.drugs.com/sfx/follistim-aq-side-effects.html

FOLLISTIM® AQ Cartridge. (n.d.). Retrieved April 18, 2017, from https://www.merckconnect.com/follistimaq/overview.html?hcpUser=yes

pmhdev. (2017). Follitropin Beta (Subcutaneous route). PubMed Health. Retrieved from https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0045885/ - by injection reference