Follitropin

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Contents

Background [1]

Glycosylated human follitropin subunit β (red) complex with follitropin receptor (dark red), glycoprotein hormone (gold), ethylene glycol and jeffamine (PDB code 4mqw)


Follitropin β injection is used to treat infertility in both males and females. Brand names for follitropin β 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 after receiving a signal from the hypothalamus. Some fertility programs such as Assisted Reproductive Technology (ART) use follitropin β, in conjunction with human chorionic gonadotropin (hCG), to help oocytes develop in women. Follitropin β is also used in men, along with hCG to increase sperm count.


Function and Clinical Use [2]

FSH stimulates the growth and healthy function of ovarian follicles. FSH in males is involved in maintaining normal levels of sperm production [3]. 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 β 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 [4]

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 [5]

The amino acid sequence and structure of follitropin β are exactly the same as that of human urinary follicle-stimulating hormone (hFSH). Follitropin β is a glycoprotein hormone that is created through recombinant DNA technology. The dimeric structure of follitropin β contains 2 glycoprotein subunits – α, consisting of 92 amino acids, and β, consisting of 111 amino acids. The α subunit is glycosylated at Asn 51 and Asn 78 the β subunit is glycosylated at Asn 7 and Asn 24.

Mechanism [6]

Follitropin β is a form of follicular stimulating hormone (FSH), which acts through a transmembrane G-protein receptor on the surface of granulosa cells of the ovaries and sertoli cells of the testis. FSH first undergoes a conformational change that forms a new pocket on its surface. Its receptor, FSHR, then inserts a sulfotyrosine residue that pocket to bind FSH, and with FSH bound the transmembrane receptor undergoes a conformational change. The conformational change by the receptor mechanically activates the G-protein, which detaches from the receptor and activates the second messenger adenylyl cyclase. Adenylyl cyclase leads to the increased production of cAMP that in turn activates a protein kinase cascade through protein kinase A. One protein kinase cascade that could be activated is the PI3K (phosphoinositide-3-kinase)/AKT pathway, which leads to the growth and maturation of germ cells.

3D structures of follitropin

Updated on 13-January-2019

4ay9, 4mqw, 1xwd – hFTR β + FTR receptor + glycoprotein hormone – human

References

  1. pmhdev. (2017). Follitropin Beta (Subcutaneous route). PubMed Health. Retrieved from https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0045885
  2. 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
  3. Hillier, S. G. (1994). "Current concepts of the roles of follicle stimulating hormone and luteinizing hormone in folliculogenesis. Human Reproduction", 9(2), 188–191. [1]
  4. Follistim AQ Side Effects in Detail. (n.d.). Retrieved April 18, 2017, from https://www.drugs.com/sfx/follistim-aq-side-effects.html
  5. DrugBank (Ed.). (2017, April 17). Follitropin β. In DrugBank. Retrieved from https://www.drugbank.ca/drugs/DB00066
  6. Telikicherla, D., Ambekar, A., Palapetta, S. M., Dwivedi, S. B., Raju, R., Sharma, J., … Pandey, A. (2011). A comprehensive curated resource for follicle stimulating hormone signaling. BMC Research Notes, 4, 408. https://doi.org/10.1186/1756-0500-4-408

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