Male Phys Flashcards
Where does spermatogenesis occur?
in the seminiferous tubules of the testes
- it is staggered thru/o the ST’s so that all developmental phases are present at 1 time
compare and contrast female vs male gamete prodxn
What is a spermatogenic wave?
what is the benefit behind this?
what is the daily sperm production?
How does age affect spermatogenesis?
spermatogenic wave time it takes for reappearance of the samee stage w/in a given segment of the seminiferous tubule
- BENEFIT: spermatozoa are produced continually and mature sperm are always available
- 100 million sperm produced per day!
- spermatogenesis continues thru/o life but prodxn decreases with age
- positively correlated with testosterone levels
Describe the hormonal regulation of spermatogenesis
which cell is directly related to spermatogenesis?
the sertoli cell!
simple linear [direct] relationship b/w sertoli cell # & daily sperm prodxn
which spermatogenesis cells die with age?
What consequences does this have?
Leydig cells!
there is a (+) linear relationship b/w leydigs and sperm prodxn:
_Consequences: _[leydig produce testosterone]
- decreased total & free test. levels
- leads to increased abd fat & decreased muscle mass
- [and decreased sperm prdxn]
- leads to increased abd fat & decreased muscle mass
What is andropause?
What are causes it?
what are the Sx’s?
Dx?
Tx?
androgen deficiency with aging
-
Cause: decrease testicular fxn
- loss of spermatocytes, Leydigs, sertolis–>decrease test prodxn –>^^GnRH & LH/FSH
-
Sx’s: +/- erectile dysfxn
- weight gain [met. shifts, reduced activity & gynecomastia]
- also due to E:test ratio changes
- weight gain [met. shifts, reduced activity & gynecomastia]
- Dx: measure morning total test [more than 1 #, follow up w/ FSH/LH levels]
- Tx: HRT, sleep & eat well, exercise, Viagra-like drugs for ED
What are testosterone target organs?
WHat organs produce 5a reductase?
targets: muscle, seminal vesicle, epididymis, bone
5a-reductase: prostate, external genitalia, & skin
What is testosterone made by?
What do some tissues convert it to?
How does it circulate through the body [form]?
What does it bind to?
- test is made by leydig cells (95%) and adrenal gland (5%)
- test –> dihydrotestosterone [DHT] in target tissues that have 5a-reductase
- circulating testosterone is usually bound to SHBG [sex hormone binding globulin] aka androgen binding globulin ABG when made by sertolis
- males: 0.6 mcg/dL
- females: 0.03 mcg/dL
- binds to androgen R [AR] binds all androgens–> acts a transcription factor
What effects do androgens have?
-
promote health & fxn of:
- seminal vesicles, prostate, genital tract, external genitalia, hair growth patterns, voice change
-
Anabolic effects:
- muscle building
- N+ balance; increase in protein synthesis
- bone growth & closure of epiphysis
- Na+ & h2o retention
- muscle building
clinically when do we use androgens?
- androgenic effects: hypogonadism & hypopit fxn
- anabolic effects: trauma, debilitating dz
- enhance athletic performance [BAD DONT DO IT]
wHICH HAVE ^^ 1st pass metabolism, natural vs. synthetic androgens?
1st pass metabolism= natural>synthetic
- synthetics are weak or inactive metabolites?
What is methyl testosterone?
what is oxandrolone?
methyl testosterone: test. analog
- orally active, and esterification retards absorption & metabolism
- SE: hepatotoxic
- acute cholestasis [1%] & ^^risk of tumor incidence
- USE; Test. hormone replacement
oxandrolone: DHT derivitive
- orally active, cannot be converted by aromatase
- low risk of hepatotoxicity
- anabolic steroid–>promotes muscle growth
What are advers/SE’s of androgen therapy?
- Growth interruption (premature bone closure) in growing youth
- Aromatization of androgens to estrogen occurs at bone plates
- Estrogen is critical for epiphyseal fusion in both young men and women.
- •Priapism
- •Sodium & water retention
- •Jaundice
- •Hepatic carcinoma
- •Hypogonadism upon cessation due to long-term reduction in HPG axis
- •Aggressive behavior
- •Urinary obstruction
What are the gender specific adverse SE’s of anabolic steroids?
MEN:
- gynecomastia, testicular shrinkage, impotence, reduced sperm count
- baldness
WOMEN:
- menstrual irregulariteis [shorter & lighter]
- clitorus enlargement
- ^^facial & body hair
Why do androgen anabolic steroids have so many SE’s?
- they can bind to AR, glucoC R, P & E R’s ==> multiple effects
- aromatization of AAS’s can render many adverse E effects
When would we do medical castration?
How would we do this medically?
Purpose:
- interfere w/ precocious puberty
- Tx: androgen dependent cancers
- reduce libido
Meds:
- AR antagonists
- nonpulsatile GnRH agonists
- ” “ antagoniists
in postemenopausal women, where are nearly all estrogen/androgens made?
Would GnRH agonists/antagonists work on these pts?
locally in peripheral tissues from adrenal steroid precursor DHEA
- NO, because GnRH ant-/agonists wipe out testicular prodxn of androgens but not locally
what drug should we use if we want to shut down HPG-axis?
use GnRH agonist/antagonist
if the goal is to reduce AR signaling in prostate gland what would we use?
AR antagonists and/or 5a reductase inhibitors and/or GnRH antagonists
What is cyproterone acetate?
what si it used for
MOA: androgen antagonist
- also has strong activity as a progestin too
USE:
- to reduce excessive sex drive in men
- tx hirsuitism in women [in combo with E–> shifts balance to E dominance]
what is gonadorelin?
uses?
acetate salt of human recombinant GnRH–> agonist
- bind GnRH-R’s–> stimul8 release of FSH/LH–>increase test
- used for fxnl assessment of gonadal response
- male infertility: 3-6 mo of pulsatile infusion improves sperm #s
**continuous delivery shuts down HPG axis, whereas pulsatile or single dose is stimulatory
What are degarelix?
Ganirelix & Cetrorelix?
- relix = GnRH antagonists
- binds GnRH-R’s in pit–> blocks axn of GnRH–> decreases FSH/LH –> decreases test prdxn
Degarelix: for advanced prostate cancer
- male chemical castration
- BPH
- assisted reprodxn under investigation
Ganirelic, CEtrorelix: assisted reprodxn 4 ovarian hyperstim=>blox premature LH surge in females
- major diff from GnRH agonist is the antagonist DOESNT have initial LH/FSH^^ phase
How does an erection happen?
