Urofollitropin, Native Human Follicle-stimulating hormone (FSH)
The product is a purified form of follicle-stimulating hormone (FSH) that is manufactured by extraction from human urine. It consists of two non-covalently linked, non-identical glycoproteins designated as the alpha- and beta- subunits. The alpha- and beta- subunits have 92 and 111 amino acids. The alpha subunit is glycosylated at Asn 51 and Asn 78 while the beta subunit is glycosylated at Asn 7 and Asn 24. The product is important in the development of follicles produced by the ovaries.
Used for the treatment of female infertility, the product or follicle stimulating hormone (FSH) stimulates ovarian follicular growth in women who do not have primary ovarian failure. FSH, the active component of the product is the primary hormone responsible for follicular recruitment and development.
Mechanism of action:
FSH binds to the follicle stimulating hormone receptor which is a G-coupled transmembrane receptor. Binding of the FSH to its receptor seems to induce phosphorylation and activation of the PI3K (Phosphatidylinositol-3-kinase) and Akt signaling pathway, which is known to regulate many other metabolic and related survival/maturation functions in cells.
Follicle-stimulating hormone (FSH) is a key hormone produced by the pituitary gland located at the base of the brain. Its discovery traces back to the early 20th century alongside other pituitary hormones. Initially, it was identified and studied under the broader category of gonadotropins, hormones influencing the function of gonads—the ovaries in women and testes in men.
Classified under glycoprotein hormones, FSH is a complex molecule consisting of two subunits: alpha and beta. While the alpha subunit is shared amongst other hormones including thyroid-stimulating hormone (TSH) and human chorionic gonadotropin (hCG), the beta subunit is unique to FSH, determining its specific biological function. The FSHB gene, located on chromosome 11p13, encodes the beta subunit, and variations affecting this locus can lead to functional alterations in FSH production and activity.
FSH plays indispensable roles in human reproduction. In women, it governs the growth and maturation of ovarian follicles, which contain and release eggs during the menstrual cycle. FSH also upturns the production of estradiol, an essential female sex hormone. In men, FSH stimulates the production and maturation of sperm within the testes.
FSH-Related Signaling Pathways
FSH binds to its receptor (FSHR) on the surface of target cells, which triggers intracellular signaling cascades. The primary signaling pathway is the cyclic AMP (cAMP)/Protein kinase A (PKA) pathway. Upon FSH binding, FSHR activates the G protein, which then stimulates adenylate cyclase to convert ATP to cAMP. cAMP activates PKA, which phosphorylates various proteins and nuclear transcription factors, leading to genomic responses such as increased gene transcription.
FSH also activates the phosphoinositide 3 kinase (PI3K)/Akt pathway, crucial in cell survival, proliferation, and growth, and the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) pathway, which regulates cell differentiation and proliferation. Alterations in these pathways could lead to reproductive disorders.
FSH Related Diseases
Altered FSH levels can result in various reproductive disorders. Elevated FSH levels can indicate primary gonadal failure, such as premature ovarian failure in women and testicular failure in men. Lower-than-normal FSH levels could lead to problems in sperm or egg production, resulting in infertility.
FSH also plays a role in other medical conditions. For instance, in polycystic ovary syndrome (PCOS), FSH levels are often lower, resulting in an abnormal increase in the luteinizing hormone (LH) to FSH ratio, leading to the development of small ovarian cysts. In menopause, FSH levels rise as the ovaries' function declines.
The Application of FSH in Medicine
FSH has substantial applications within the field of reproductive medicine. Artificially produced FSH, known as "recombinant FSH", is frequently used in fertility treatments such as in-vitro fertilization (IVF), promoting the development of multiple eggs. It's also used in conjunction with LH treatments in men suffering from congenital hypogonadotropic hypogonadism to stimulate spermatogenesis.
Drug Candidates related to FSH
Numerous drugs mimic or influence the action of FSH. Menotropins are medications containing FSH and LH used in fertility treatments. Urofollitropin is a purified form of FSH used for the same indications. Conversely, Ganirelix and Cetrorelix are used to block FSH action, preventing premature ovulation during assisted reproductive procedures.
Understanding FSH's role in reproduction allows us to comprehend numerous infertility causes and provides potential therapeutic targets in reproductive medicine. While significant progress has been made in understanding and applying FSH in clinical use, ongoing research will continue to unveil the intricate intricacies of this critical hormone.
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