Hormones and Their Therapeutic Uses Quiz

Overview of Hormones and their Therapeutic Uses

• Hypoglycemia is the most common complication of insulin administration due to various factors such as excessive insulin, omission of a meal, and increased physical activity.
• Glucagon, used to treat insulin-induced hypoglycemia, is also used as a diagnostic aid in radiological examinations of the gastrointestinal tract.
• Glucagon is traditionally extracted from bovine or porcine tissue, but now, most glucagon is produced using recombinant means such as Novo Nordisk's "GlucaGen" and Eli Lilly's recombinant glucagon using engineered E. coli.
• Human growth hormone (hGH) is a polypeptide hormone synthesized in the anterior pituitary that promotes normal body growth, lactation, and influences various aspects of cellular metabolism.
• hGH displays significant species specificity and is only biologically active in humans when isolated from other primates.
• hGH primarily displays an anabolic activity and a deficiency in its secretion during active body growth results in pituitary dwarfism, while its overproduction results in gigantism or acromegaly.
• hGH extracted from human pituitary glands was first used to treat pituitary dwarfism in 1958 but was stopped due to a link between treatment and Creutzfeld-Jacob disease (CJD) discovered in 1985.
• All hGH preparations are now derived from recombinant sources, and over 20,000 people receive rhGH therapy.
• Gonadotrophins regulate reproductive function and development of secondary sexual characteristics produced by the pituitary and reproductive and associated tissue.
• Follicle-stimulating hormone (FSH) and Luteinizing hormone (LH) play critical roles in the development and maintenance of male and female reproductive function, while human chorionic gonadotrophin (hCG) plays a central role in maintaining support systems for the developing embryo during early pregnancy.
• FSH and LH are stimulated by a hypothalamic peptide, gonadotrophin-releasing hormone (GnRH).
• FSH targets Sertoli cells in the testis walls and plays a major role in sperm cell production in males.

Gonadotrophins and Their Medical and Veterinary Applications

• Sertoli cells support spermatids during spermatogenesis and produce inhibin to regulate FSH.
• FSH stimulates granulosa cells in ovarian follicles to promote follicular growth and estrogen synthesis.
• The market for gonadotrophins is substantial, with the hCG market generating $688 million in 2017 and expected to reach $1.239 billion by 2025.
• Gonadotrophins are used to treat infertility, with menotropins and hCG used to stimulate follicular maturation and ovulation in females.
• Overdose of gonadotrophins can lead to multiple follicular development and the risk of multiple pregnancies.
• Gonadotrophins are also used in veterinary medicine to induce a superovulatory response in valuable animals, with porcine FSH and LH typically used.
• The use of porcine gonadotrophins minimizes the risk of disease transmission between species.
• Recombinant human FSH (rhFSH) has proven clinically effective in stimulating follicular growth in females and treating hypogonadism in males.
• Ovitrelle, produced by Serono, is an example of an rhFSH approved for medical use in Europe and the US.
• Menotrophin, a preparation of FSH-enriched extracts from human urine, was previously a major source of medically used LH and FSH.
• hCG exhibits similar biological activities to LH and is extracted from the urine of pregnant women.
• Veterinary applications of gonadotrophins involve recovering embryos from animals after superovulation and implanting them into surrogate mothers.

Overview of Therapeutic Enzymes and their Applications

• Asparaginase is an enzyme that inhibits the proliferation of leukaemia cells by hydrolysing plasma asparagine.
• Asparaginase from E. coli, Erwinia, Pseudomonas, and Acinetobacter have been effective in inhibiting growth of various leukaemia's and other transformed cell lines.
• Therapeutically useful asparaginases must display a high substrate affinity as the plasma concentration of asparagine is quite low (~40 μmol L-1).
• Side effects of asparaginase treatment include severe nausea, vomiting, diarrhoea, and compromised liver and kidney function due to transient asparaginase deficiency in various tissues.
• DNase is an enzyme that can breakdown DNA and reduce the viscosity of respiratory mucus in cystic fibrosis patients.
• Highly purified recombinant human DNase (rhDNase) has been used to treat cystic fibrosis since 1993 and is safe and effective.
• α-Galactosidase is approved for long-term enzyme replacement therapy in patients with Fabry disease, a genetic disease of lipid metabolism.
• Two recombinant α-galactosidases are on the market: Fabrazyme and Replagal.
• Superoxide dismutase (SOD) is an enzyme that reduces tissue damage due to irradiation or other conditions that generate O2-.
• Increased generation of O2- and/or reduced SOD levels have been implicated in various pathological conditions, including ageing, asthma, neurodegenerative diseases, and inflammatory tissue necrosis.
• SOD isolated from bovine liver or erythrocytes has been used as an anti-inflammatory agent.
• Human SOD has been expressed in several recombinant systems and is being evaluated to assess its ability to prevent tissue damage induced by exposure to excessively oxygen-rich blood.