LECTURE 12 (sex hormones + ethanol metabolism) Flashcards
What are the three different types of oestrogen?
- Estrone (E1)
- Estradiol (E2)
- Estriol (E3)
POTENCY: Estradiol > Estrone > Estriol
What is the difference between Estrone, Estradiol and Estriol?
- Estrone = the only oestrogen your body makes after menopause
- Estradiol = the most common type in women of childbearing age
- Estriol = the main oestrogen during pregnancy
Estrogen synthesis happens in ___________ _________
Ovarian follicles
Explanation: Ovarian follicles consist of OOCYTE surrounded by THECA & GRANULOSA cella
What is the importance of LH and FSH in oestrogen synthesis in females?
- Hypothalamus secretes GONADOTROPIN RELEASING HORMONE (GnRH) which causes the pituitary gland to release LH and FSH
- LH acts on THECA CELLS and causes the conversion of CHOLESTEROL to ANDROSTENEDIONE via DESMOLASE
- FSH acts on GRANULOSA CELLS and causes the conversion of ANDROSTENEDIONE to ESTROGEN via AROMATASE
Granulosa cells also produce ____________ which suppresses FSH
Inhibin
What does LH and FSH act on in males and females?
FEMALES
- Ovaries
- LH -> Theca cells
- FSH -> Granulosa cells
MALES
- Testes
- LH -> Leydig cells
- FSH -> Sertoli cells
What are the properties of Leydig cells?
- Secrete testosterone
- Stimulated by LH
- Testosterone - most potent, major circulating androgen in males
What are the properties of Sertoli cells?
- Regulate spermatogenesis
- Support and nourish developing spermatozoa
- Secrete inhibin -> inhibit FSH
- Secrete androgen-binding protein -> maintain local levels of testosterone
- Tight junctions between adjacent Sertoli cells form blood-testis barrier -> isolate gametes from auto-immune attack
What is Testosterone converted into in peripheral tissues?
Dihydrotestosterone
Explanation: Conversion by 5-ALPHA REDUCTASE -> conversion since DHT is more potent, stable and binds androgen receptors more strongly
What is used to treat Prostatic hyperplasia and hair loss in men?
5-alpha reductase inhibitor (Finasteride)
What is Testosterone converted into in adipose tissue and Leydig cells?
Estradiol
Explanation: Conversion occurs by AROMATASE
What are the properties of Ketoconazole?
- Antifungal medication (blocks ergosterol synthesis in fungi)
- Potent inhibitor of 17,20-lyase -> decreased androstenedione/testosterone -> GYNECOMASTIA (overdevelopment/enlargement of breasts in men)
- Inhibits 17-alpha hydroxylase & desolate -> blocks cortisol synthesis -> treats Cushing’s syndrome
Describe Ethanol Metabolism
- Occurs in Liver
- Ethanol -> Acetaldehyde via ALCOHOL DEHYDROGENASE (cytosol) then Acetaldehyde -> Acetate via ALDEHYDE DEHYDROGENASE (mitochondria)
What are Excessive ethanol consumption consequences?
- CNS depression
- Hypoglycaemia
- Ketosis
- Lactic acidosis
- Accumulation of fatty acids
- Hyperuricemia
- Hepatitis and cirrhosis
- INCREASED NADH (trigger for all biochemical problems!!!)
What are the consequences of NADH stopping the TCA cycle?
- NADH shunts oxaloacetate to malate -> Increased acetyl CoA (since citrate cannot be formed) -> increased ketone synthesis
- Decreased gluconeogenesis -> hypoglycaemia