Lecture 23: Male Reproductive Physiology Flashcards
How do these contribute to male sexual differentiation?
SRY gene
AMH & testosterone
- on the Y chromosome, TDF
- released by Sertoli and Leydig cells respectively > development of male tract and external genitalia
Draw the trends for male gonadotropin secretion through these stages: Fetus Childhood Puberty Adult Senescence
Ok
How is puberty initiated?
Pulsatile GnRH > pulsatile FSH >LH > pulsatile testosterone and estradiol > puberty characteristics
Long acting GnRH does not trigger puberty
Sertoli cells
Leydig cells
- provide sperm nutrients and secrete fluid that transport sperm to epididymis
- make and secrete testosterone
Draw the synthesis of androgens in Leydig cells from cholesterol ester to DHT
Ok
What happens to testosterone after it is synthesized?
- concentrated in the tubules by binding to androgen binding protein
- bound to SHBG and albumin so it can circulate in blood (must be freed to be activated)
How is estrogen synthesized in males?
Why is it important?
- aromatase converts testosterone to estradiol in tubules
- important in enhancing spermatogenesis
What is the role of LH?
increase P450SCC affinity for cholesterol and synthesis of more of the enzyme > stimulate the conversion of cholesterol to pregnenolone
Once in the circulation, how does Testosterone implement its effects?
diffuse to target cell and binds to Androgen receptors (AR) in the nucleus > direct protein synthesis in target cell
What is the role of DHT?
-binds to ARs, plays role in development of fetal external genitalia, hair, sebaceous gland, prostate growth
(5a reductase deficiency causes ambiguous genitalia)
How are testosterone and metabolites excreted?
-mostly in urine (as urinary 17-ketosteroids)
Which androgens do these tissues produce?
Testis
Adrenal
Peripheral tissues
- cholesterol to DHT/estradiol (testosterone pathway)
- cholesterol to androstendione
- testosterone to DHT/estradiol
What is the importance of testosterone during fetal development?
Presence of fetal testosterone during the 2nd month = development of penis and scrotum, internal male tract and testicular descent
Absence = default to female tract
What is the importance of testosterone during puberty?
-responsible for muscle growth, epiphyseal plate closure, voice deepening
BPH
cause
sx
tx
- urethra constriction due to enlarged prostate, not necessarily elevated DHT, but possibly more DHT receptors
- can’t pee like you want to pee (can be restricted or urgent)
- 5a reductase inhibitors = inhibits DHT formation which is responsible for prostate growth
Draw the pathway of testosterone action from Leydig to Sertoli cell
ok
What are the functions of Sertoli cells?
Supportive: blood testis barrier, phagocytosis, nutrient transfer
Exocrine (secretions) and Endocrine (intracellular mechanisms)
Draw the male HPG axis and the main regulatory mechanisms
Ok
Where does spermatogenesis happen?
-seminiferous tubule epithelium with spermatogenic cells and supportive Sertoli cells
Draw the process/progression of spermatogenesis
Ok
Characteristics of Division I of spermatogenesis
Characteristics of Division III of spermatogenesis
- mitotic divisions, sperm proliferation (increases in puberty)
- maturation phase/spermiogenesis (nuclear and cytoplasmic > morphologic changes on spermatids > sertoli cells release the mature spermatozoa)
Be able to label the parts of the mature spermatozoa on the image
Ok
What happens to the “leftover” residual bodies during spermiogenesis?
phagocytosed by Sertoli cells
Summary of the hormones effects on male phys: LH FSH GH Testosterone Estradiol
- induce Leydig cells to make Testosterone
- induces stertoli cells with primary spermatocytes to mature into spermatozoa
- testis growth/maintenance
- growth of germinal cells
- enhances spermatogenesiss
How is spermatogenesis regulated?
- Spermatogenesis maintained by high conc. of T diffusing into Sertoli to drive maturation of sperm
- Circulating and exogenous testosterone inhibits the activity of Hyp and AP > decrease T diffusing to Sertoli > decrease conecntration of T > decrease spermatogenesis
What happens in the epidydymis?
sperm released from testis mature for a month here via increasing their motility and decapacitation (strengthening the sperm acrosome)
Draw the trend of testosterone and sperm production throughout life
Ok
What is the role of the seminal vesicles?
-prostaglandins from seminal vesicles reacts with cervical mucus to increase receptiveness to sperm penetration (thin the mucus out) > results in peristalsi in the uterus and tubes to propel sperm to ovary to meet egg
What is the role of the prostate gland?
- releases alkaline fluids to neutralize acidity of the seminal fluid which helps sperm motility
- semen is a mixture of fluids from vas deferens, seminal vesicles and prostate + millions of sperm
How is the male tract different from the female tract?
lumen is continuous through entire pathway and connects to the urinary tract (urine and semen both exit at urethra)
Pathway of sperm out of the body:
tubules > epididymis > vas deferens > ejaculatory duct > 3 regions of male urethra
What structures are responsible for mediating an erection?
2 corpora cavernosas + 1 corpus spongiosum - made up of potential cavernous spaces that can accommodate blood
Physiology of erection:
PNS > NO to arteries supplying the cavernous spaces > Gc > cGMP > decrease Ca2+ in cell
effects: SM relaxation/vasodilation > increased vascular perm. > blood leaks to cavernous spaces > compresses veins > stimulates penile muscle contraction at base = erection
Physiology of emission (semen motility before and during ejaculation)
SNS > SM peristaltic contraction @ vas deferens and entire tract to propel the semen out
*internal sphincter of bladder closes to prevent release of semen in bladder
Physiology of ejaculation:
somatic motor neurons > rhythymic contraction of bulbospongiosus and ischiocavernosus muscles > propel semen out
What does capacitation mean?
How is this achieved?
- mature sperm activates repressed capabilities that are by contact with female fluids
- wash inhibitory factors away, weaken acrosome by losing cholesterol, increase membrane permeability to Ca2+ to increase sperm motility
Describe the sperm acrosome reaction
-Acrosomal head of sperm releases hyaluronidase (destroys the hyaluronic acid polymers around egg) and proteolytic enzymes (digest proteins that adhere the ovum) to penetrate the egg
What happens if testosterone deficiency happens at …
2-3 months gestation
3rd trimester
puberty
post-puberty
- male genitalia ambiguity
- testicular descent problems (cryptochordism) and micropenis
- poor secondary characteristics, eunuchoid features - looking prepubescent with features of opposite sex
- decreased libido, erectile dysfunction, infertility
Kallman’s syndrome:
- hypogonadotropic hypothalamic dysfunction/secondary hypogonadism
- GnRH neurons fail to migrate to hypothalamus during development. low GnRH > delayed/absent puberty, impaired smell
Kleinfelter syndrome/seminiferous tubular dysgenesis
-primary hypogonadism.testicular dysfunction
- XXY, phenotypically male, but low T due to destruction of tubules > reduced testes development and spermatogenesis
- FSH, LH usually high trying to stimulate T release
Male pattern baldness
Testicular tumor:
Germinal epithelial tumor
- caused by increased DHT, treated with 5a reductase inhibitor
- tumor produces more T than normal
- no hormones produced
What is andropause?
decreased LH sensitivity as men age
