Lecture 39-41 Flashcards
What are pre-embryonic conceptuses usually resistance to?
Teratogens
What are the odds of birthing a completely normal healthy ifant?
Less than half
When is the spontaneous abotion most likely to occur?
Weeks 1 and 2
What is an EDC?
Endocrine disruption chemicals?
What are the functions of EDCs?
- Mimic endogenous hormones
- Block endogenous hormones
What EDCs mimic?
- Estrogenic chemicals (DES)
- Androgenic chemicals (Trenbolone)
What EDCs block?
Anti androgenic chemicals (Metabolites of DDT and vinclozlin)
Does a hormonal mimic trigger a hormonal response?
Yes, which can be hindering to the organism
What kind of hormonal block doesn’t bind to the binding site directly?
Steric Hindrance
What are the four levels that xenobiotics disrupt endocrine homeostasis at?
- Hormone synthesis (steroidogenesis) via enzymes
- Transport (prohibits binding to SHBG) by keeping endocrine hormones in local circulation and contributing to bioaccumulation
- Activation/Metabolism (Aromatase use/metabolic in activation/5A-reductase) via activation at target tissues and inactivation/degradation
- Receptor Binding (androgen receptor and oestrogen receptor) via internalization
What xenobiotic often affects steroidogenesis?
Phthalates (decreased 3B-HSD)
What xenobiotics often affects the use of aromatase to convert T to Oestradiol?
- Increased atrazine
- Decreased Tributyl Tin
What xenobiotic often affects the binding to SHBG?
Pesticides
What xenobiotics often affects metabolic inactivation/sulphation?
Sulphotransferases (PAHs and PCBs)
What xenobiotic often affects the use of 5a reductase?
Finasteride (proscar/propecia)
What xenobiotic often affects binding to androgen receptors?
p,p’-DDE
What xenobiotic often affects binding to oestrogen receptors?
o,p’-DDE
What the four main categories of EDCs?
- Androgenic
- Anti-androgenic
- Estrogenic
- Anti-estrogenic
What are examples of pharmaceutical androgenic EDCs?
Androgen Receptor Agonists (Trenbolone, Trenbolone acetate)
What are examples of pharmaceutical anti-androgenic EDCs?
- Androgen synthesis inhibitors (Ketoconazole)
- Androgen receptor antagonists (flutamide)
- 5a-reductase inhibitors (finasteride (Proscar, Propecia))
What are examples of environmental anti-androgenic EDCS?
- Androgen receptor antagonists (p,p’-DDT and its metabolites, vinclozolin and its metabolites)
- Androgen synthesis inhibitors (Phthalate esters)
What are examples of pharmaceutical estrogenic EDCs?
Estrogen receptor agonists (ethinyl estradiol, eiethylstilbestrol)
What are examples of environmental estrogenic EDCs?
- Estrogen receptor agonists (o,p’-DDT and its metabolites, Bisphenol A)
- Aromatase stimulant (Atrazine)
What are examples of pharmaceutical anti-estrogenic EDCs?
Aromatase inhibitors (Letrozole (Femara))
What are examples of environmental anti-estrogenic EDCs?
Aromatase inhibitors (Tributyl tin)
What are current hypotheses as to the signs of testicular dysgenesis syndrome?
- Cryptorchidism
- Hypospadias
- Short ano-genital distance (AGD)
- Poor spermatogenesis
- Testicular cancer
What occurs in testicular dysgenesis?
- Decreased Leydig cell function -> Decreased testosterone and INSL3 production -> cryptorchidism, short AGD and hypospadias
- Decreased Sertoli cell function -> Impaired germ cell differentiation -> Impaired spermatogenesis and GCNIS Testicular cancer
- Leydig cell function and Sertoli cell function act as a positive feedback loop on each other when decreased function occurs
What is GCNIS?
Germ Cell Neoplasia in situ
What are the odds of the different locations on cryptorchidism?
- High scrotal (60%)
- Inguinal canal (25%)
- Abdominal (15%)
What is another term for Human papilloma virus?
HPV or wart virus
What areas are known to get cancer due to HPV?
- Cervix
- Vulva
- vagina
- penis
- oropharangea (mouth, tongue and throat >4 times higher in men then women)
- anus
- rectum
What is the most effective method of HPV prevention?
Early vaccination
How many types of HPV are there and which can affect the genital area?
There are over 100 types of which 40 can affect the genital area
Which forms of HPV cause the majority of HPV-related cancer and diseases?
- 6
- 11
- 16
- 18
- 31
- 33
- 45
- 52
- 58
What is special about HPV 6 and HPV 11?
Causes most benign lesions
What is special about HPV 16 and HPV 18?
Causes most malignant lesions of cervical and penile cancer
How does early exposure to Bisphenol A affect the prostate?
- Reprograms human prostate stem-progenitor cells
- Promotes self-renewal
- Increases in vivo carcinogenesis with aging
What is the most common form of ovarian cysts?
Solitary follicular, luteal or theca-lutein cysts
What is polycystic ovary syndrome?
When both ovaries are involved and studded with multiple cysts, and results in obesisty in 50% of cases (hyperinsulinemia)
What is the endocrinopathy of Polycystic Ovary Syndrome?
- Excessive androgen production
- LH:FSH ratio above 2
- Increased testosterone and androstenedione
- Increased estrogen
How does insulin regulate ovarian androgen production?
Increased androstenedione, Testoterone, DHEAS -> act on pituitary to shut off FSH and LH -> shut off estradiol and progesterone
What is DHEAS?
Dehydroepiandrosterone sulphate