Adrenal Androgens Flashcards
Where are adrenal androgens produced?
Zona reticularis of the adrenal cortex
What three adrenal androgens are released from the zona reticularis?
Dehydroepiandrosterone (DHEA)
Androstenedione
Testosterone
What receptor takes in cholesterol for steroid hormone production?
SRB1 (scavenger receptor class B member 1)
What binds to SRB1?
LDL
HDL
What regulates the synthesis of adrenal androgens?
ACTH
CASH (cortical androgen stimulating hormone)
What binds and carries androgens in the blood?
SHBG (sex hormone binding globulin)
What has a negative feedback on ACTH?
Only cortisol not any other steroid hormone
What receptor does ACTH bind to in the adrenal cortex?
MC2R (melanocortin-2 receptor)
What does cortisol inhibit?
CRH from hypothalamus
ACTH and CASH from anterior pituitary
What are two different forms of DHEA?
DHEA
DHEAS (sulfate)
Which DHEA has a longer half-life?
DHEAS
Where is testosterone mostly created?
Leydig cells in the testes (95%)
Only 5% created in the zona reticularis
How is testosterone carried in the blood?
98% binds to albumin and SHBG
What are the most abundant steroid hormones in the bloodstream?
DHEA
DHEAS
What is adrenarche?
Period in time (10-11 years of age) in which the zona reticularis is developed and begins to create androgens in an increased level without increased cortisol
When does adrenarche occur?
Age of puberty 10-11 years old
Where does DHEA go in premenopausal females?
Ovary for estradiol (E2) and testosterone formation
Mammary gland
Where does DHEA go in males?
Testes for testosterone production
Prostate
What does 11B-HSD2 do?
Converts cortisol to cortisone
Free androgens (DHT/Estradiol) are highly metabolized where in the body?
Liver and excreted by the kidney
What are the metabolites of DHT and Estradiol?
Androsterone
Etiocholanolone
Effects of DHEA?
Pubertal growth spurt (essentially everything involved in growing)
Effect of estrogen on bones?
Epiphysis fusion of bones and mineralization
Effect of DHEA on immune system?
Antagonizes cortisol
What is the effect of DHEA on endothelial function?
Increases eNOS -> NO production causing vasodilation
What does 5alpha-reductase do?
Converts testosterone to DHT
What does aromatase do?
Converts testosterone to estradiol
What does a deficiency in aromatase or estrogen receptor cause?
Failure to fuse long bones
Osteoporosis
What develops from the Wolffian mesonephric duct?
Epididymis
Vas deferens
Seminal vesicle
Ejaculatory duct
What develops from the Mullerian paramesonephric duct?
Fallopian tubes
Uterus
Upper part of vagina
What genes on the Y chromosome determines the sex of the fetus?
SRY gene
SRY gene in gonads causes formation of Sertoli cells, what do the Sertoli cells release?
Mullerian inhibiting substance (MIS)
What does MIS cause?
Mullerian duct degeneration
SRY gene in gonads causes formation of Leydig cells, what do the Leydig cells release and the effect?
Testosterone
Causes Wolffian duct development
What medical problem in women has the highest negative impact on morbidity?
Menopause
What occurs to sodium and potassium levels in 21-alpha hydroxylase deficiency?
Hyponatremia
Hyperkalemia
Why do you have Hyponatremia and hyperkalemia in 21-alpha hydroxylase deficiency?
Decreased aldosterone not
What does a 21-alpha hydroxylase deficiency cause in steroid hormone production?
Cannot produce mineralocorticoids or glucocorticoids so it is shunted to formation of androgens
Most common congenital genetic enzymatic defect in steroid hormone synthesis?
21-hydroxylase (same as 21-alpha hydroxylase)
Second most common congenital genetic enzymatic defect in steroid hormone synthesis?
11-beta hydroxylase
What occurs in 21 alpha-hydroxylase deficiency?
ACTH loss of negative feedback
Increased androgen shunting
Virilization
What is Virilization?
Presence of masculine traits
What occurs in 11 beta-hydroxylase defects?
Increase in deoxycortisol/deoxycorticocosterone
Decrease but not loss of cortisol negative feedback
Increased androgen shunting/Virilization
Salt and water retention (hypertension)
Why do you still have mild ACTH negative feedback and hypertension in 11 beta-hydroxylase defects but not 21 alpha-hydroxylase defects?
Because in 11 beta-hydroxylase you have a build up of the intermediates (deoxycortisol/deoxycorticocosterone) that have mild effects on ACTH and large effects on ENaC (increased Na retention)
Effects of 17 alpha-hydroxylase deficiency?
Increase in mineralocorticoids and aldosterone
What is androgen insensitivity syndrome?
Mutation in androgen receptor such that tissues do not respond to testosterone or other androgens
What gonads develop in androgen insensitivity syndrome?
The testes
What do individuals develop as externally with androgen insensitivity syndrome?
Female (they are XY males though)
How is androgen insensitivity syndrome detected?
Amenorrhea (lack of menstruation)
Proper development of what is dependent on DHT?
Penis
Prostate gland
What occurs in 5-alpha reductase type 2 disorder?
Males are born with female-appearing external genitalia
Hypospadias (penis doesn’t enlarge)
What occurs at puberty in 5 alpha-reductase disorder?
Large levels of circulating testosterone stimulate development of male structures
What does the drug Abiraterone do?
Inhibits both 17,20-lyase and 17 alpha-hydroxylase
What does Abiraterone administration result in?
Inhibition of androgen and glucocorticoid synthesis and shunting to mineralocorticoid synthesis
What gene does CYP17A1 code for?
17,20-lyase and 17 alpha-hydroxylase
When is Abiraterone administered?
Prostate hyperplasia
Prostate cancer
What is given with Abiraterone to counteract the effects of decreased glucocorticoids?
Prednisone
What is Kennedy’s disease?
X-linked bulbospinal neuropathy
What occurs in Kennedy’s disease?
Androgen receptor mutation
