Male Reproductive Physiology Flashcards
What determines genetic sex?
XX or XY
Why is there a delay in formation of testes vs ovaries?
there is no anti-mullerian hormone production, so the mullerian tract can form to make the internal genitalia
What week is the fetus bipotential (neither m or f)?
week 5
When do the testes begin to develop?
weeks 6-7 d/t production of anti-mullerian hormone
When do ovaries begin to develop?
week 9
What determines gonadal sex?
testes or ovaries
What determines phenotypic sex?
physical characteristics of internal and external genitalia
**determined by HORMONAL output from gonads
When does GnRH (and subsequently FSH and LH) begin to rise after birth?
puberty
What initiates puberty in terms of hormones?
pulsatile secretion of GnRH–> pulsatile FSH and LH
What are responsible for appearance of secondary sex characteristics?
increased circulating levels of sex steroid hormones
What stimulates secretion of gonadal steroid hormones: testosterone and estradiol?
pulsatile secretions of FSH and LH
How did they discover pulsatile GnRH was necessary to start puberty?
GnRH analogue given:
- pulsatile: puberty initiated, reproductive fxn established
- long acting: no puberty
What are the 2 main fxns of the testes?
- spermatogenesis
- secretion of testosterone
What is the main fxn of the scrotum?
maintain lower temperature (1-2 below BT) for spermatogenesis
What is the main fxn of the epididymis?
primary location for maturation and storage of sperm
What is the fxn of the prostate gland?
secretes milky aqueous solution rich in citrate, Ca2+ and enzymes
What is the fxn of the vas deferens?
- ampulla provides another storage area for sperm
- secretes fluid rich in fructose and citrate
What is the fxn of seminal vesicles?
secretes fluid rich in FRUCTOSE, citrate, prostaglandins and fibrinogen
Where are Leydig cells located?
between seminiferous tubules in testes
What is the anatomical make-up of the adult testis?
80% seminiferous tubules
20% CT interspersed with Leydig cells
What are seminiferous tubules?
epithelium formed by Sertoli cells with interspersed germ cells
–>contain spermatogonia and spermatozoa
What are spermatogonia?
immature germ cells located near PERIPHERY of seminiferous tubule in testis
What are spermatozoa?
mature germ cells located near LUMEN of seminiferous tubule of tesis
Where are spermatogonia and spermatozoa located in seminiferous tubules?
ogonia at periphery, ozoa near lumen
What is the general fxn of Leydig cells?
synthesize and secrete testosterone
What are the general fxns of Sertoli Cells?
- provide nutrients to differentiating sperm
- form tight jxn with each other for blood barrier b/t blood and testes
- secrete aqueous fluid into lumen of seminiferous tubules to help transport sperm to epididymis
What androgens are secreted by the testes?
testosterone (most abundant)
dihydrotestosterone
androstenedione
What is testosterone converted to in target tissues?
dihydrotestosterone (DHT)
What is the major androgenic hormone that is synthesized and secreted by Leydig cells of testes?
testosterone
What do testes lack so they can’t synthesize gluco- or mineralocorticoids?
21B and 11B-hydroxylase
What enzyme do testes have that converts androstenedionen to testosterone?
17B-hydroxysteroid dehydrogenase
What is the end product of steroid synthesis in the testes?
Testosterone
–>not DHEA and androstenedione like in adrenal gland
Where is testosterone concentrated and bound to androgen binding protein (ABP)?
lumen of seminiferous tubules
What enzyme is in peripheral tissue that converts testosterone to dihydrotestosterone?
5a-reductase
What is most of circulating testosterone bound to?
sex hormone binding globulin (SHBG)
plasma proteins
albumin
Is testosterone active in all tissues?
NO–>prostate gland, external genitalia of male fetus, skin and liver use DHT
What are the main steroidogenic cells in the testis?
Leydig cells
Where is cholesterol synthesized in testes?
Leydig cells de novo
–>can also get LDL and HDL via circulation
What lipase generates free cholesterol in Leydig cells?
hormone-sensitive lipase (HSL)
–>converts cholesterol esters to free cholesterol
What is cholesterol converted to in Leydig cells?
pregnenolone for androgen production
–>transferred within mito membranes via StAR
Are estrogens formed in males?
Yes, small amounts via Sertoli cells (product of testosterone–>estradiol)
–>high amounts in seminiferous tubules d/t role in spermatogenesis
What accounts for more than 80% of total male estrogen production?
as product of testosterone and androstenediol via tissues, especially ADIPOSE TISSUE
What is the RLS in synthesis of testosterone?
conversion of cholesterol to pregnenolone in Leydig cells
What is the mito pathway in testosterone synthesis?
CYT P450 cleaves side chain from carbon @ 20 of cholesterol
–>cholesterol to pregenolone
What carries testosterone into peripheral circulation?
bound to ABP in seminiferous tubules–> carried into circulation by SHBG and albumin
What regulates the overall rate of testosterone synthesis?
LH
What stimulates the conversion of cholesterol to pregnenolone in Leydig cells?
LH
–>increases affinity of P450 for cholesterol
–>stimulates synthesis of P450 enzyme
When does testosterone production begin in fetus?
Week 7-8
Where are androgen receptors located?
Males: prostate, testis (sertoli, leydig, myoid), epididymis, seminal vesicles
Females: ovary, mammary glands, uterus
Non-repro: CNS, AP, thyroid, skin, liver, etc.
What is the fxn of androgen receptor complex?
directs protein synthesis via nuclear receptor
Does testosterone or DHT bind androgen receptors with higher affinity?
DHT
Deficiency of what enzyme results in ambiguous external genitalia?
5a-reductase
–>DHT plays important role in causing changes at puberty
What is the most important biological form of testosterone?
free testosterone (2% blood)
- ->68% circulating bound to SHBG
- -> 38% bound to albumin
How is testosterone excreted?
urine as 17-ketosteroids
Peripheral tissues convert testosterone to what?
convert it to estradiol via aromatase
Testes convert testosterone to what?
convert to DHT via 5a-reductase
If testosterone is present in the fetus, what develops?
penis, scrotum
If there is not testosterone present in the fetus, what develops?
clitoris, vagina
Fetal actions based on testosterone
differentiation of internal male genital tract (epididymis, vas deferens, seminal vesicles)
What causes descent of testes into scrotum during last 2-3 months of pregnancy?
testosterone
What is the term for lack of testes descent?
cryptorchidism
What are actions of testosterone @ puberty?
- increase muscle mass
- pubertal growth spurt
- closure of epiphyseal plates
- growth of penis and seminal vesicles
- deepening of voice
- spermatogenesis
- libido
What is responsible for fetal differentiation of the external male genitalia?
DHT
–>penis, scrotum, prostate
What action does DHT have in males?
male hair distribution
–>male pattern baldness
sebaceous gland activity
growth of prostate
What can 5a-reductase inhibitors be used for?
treat male pattern baldness and BPH
–>DHT causes male pattern baldness and prostate growth
What are anabolic actions of androgens?
- RBC production
- sebaceous gland secretion
- controls protein anabolic effects
- linear body growth and closure of epiphyses
- ABP synthesis
- maintains secretions of sex glands
- regulates behavioral effects (libido)
Are concentrations of DHT in protatic tissue higher in men with BPH?
NO
What are classic signs and sx of BPH?
urinary frequency, urgency, nocturia
–>difficulty initiating or maintaining a stream
–>dribbling and feeling of postvoid fullness in bladder
What men develop BPH?
older men
–>80% by age 80
What stimulates Sertoli cells to produce inhibin, ABP, aromatase and protein synthesis?
testosterone and FSH
What does inhibin do?
inhibits FSH release
What provides local testosterone supply to developing spermatogonia?
binding of testosterone to ABP in lumen of seminiferous tubules
What cell produces antimullerian hormone?
sertoli cells
Where does spermatogenesis occur?
along seminiferous tubules
What distinct populations of cells line the seminiferous tubules?
- spermatogenic cells
- –>develop into spermatozoa
- Sertoli cells
- ->supportive and nutrient fxn
How long does spermatogenesis take?
64 days
–>staggered to allow maturation in stages every 16 days
What are the 3 stages of spermatogenesis?
1: mitotic divisions
2: meiotic divisions
3: spermiogenesis
What line the basement membrane of seminiferous tubules?
spermatogonia
–>end product of mitotic division
Describe pathway from primary spermatocyte to spermatozoa
-Primary spermatocyte (diploid)
complete Meiosis 1
-Secondary spermatocyte (haploid)
complete Meiosis 2
-Spermatids
spermiogenesis
-SpermatozoaWhy do spermatids undergo spermiogenesis?
to mature into spermatozoa
–>ends in testis with release from sertoli cells
What is the proliferative phase at puberty that results in primary spermatocytes?
mitotic division
–>stem cells divide to produce daughter spermatogonia–> primary spermatocytes
What occurs in meiosis of spermatogenesis?
- primary spermatocytes undergo 2 meiotic divisions
1: produces 2 secondary spermatocytes (haploid duplicated)
2: spermatocytes produce 2 spermatids (haploid unduplicated)
As spermatids mature to spermatozoa, what destroys the residual body?
Sertoli cells phagocytize
What is secreted by anterior pituitary and stimulates Leydig cells to secrete testosterone?
LH
What is secreted by anterior pituitary and stimulates Sertoli cells to nurse and form sperm?
FSH
Spermiogenesis won’t occur without what stimulation?
FSH
spermiogenesis=maturation
What hormone is necessary for controlling background metabolic fxn of testes?
growth hormone
Lack of what hormone causes deficient or absent spermatogenesis–>infertilitly?
growth hormone
What hormone promotes early division of sperm?
growth hormone
What is essential for growth and division of testicular germinal cells (beginning of sperm formation)?
testosterone
What might be essential for spermatogenesis and is formed by testosterone when + by FSH?
estrogens
What role do FSH and LH play in the stimulation of spermatogenesis?
FSH + primary spermatocyte
LH–> Leydig cell–> testosterone–> secondary spermatocyte
What effect does administration of exogenous testosterone have on spermatogenesis?
insufficient spermatogenesis d/t LH at lower than nml levels
–>androgens exert greater negative feedback on HPT axis
Where do sperm spend a month in for maturation after release from testis?
epididymis
–>increase motility
Where does decapacitation occur?
epididymis
–>prevents acrosomal reaction before contact with egg
Where can mature sperm be stored for several months?
epididymis
How do prostaglandins from seminal vesicles aid in fertilization?
- makes cervical mucus less thick so sperm can more easily
- causes reverse peristaltic contractions in uterus and tubes so sperm can move toward ovaries
What is the final pH of semen?
7.5 to neutralize acidity
What is maximal live span of ejaculated sperm?
24-48 hrs @ rt
–>2-6ml of 20-200 million sperm
What is the pathway of sperm from testis to penis?
efferent ductules of testis–> epididymis–> vas deferens–> ejaculatory duct–> prostatic urethra–> membranous urethra–> penile urethra
What are the 2 main difference between the male and female repro tracts?
1: males have continuous lumen from seminiferous tubules to end of male tract (tip of penile urethra)
2: male tract connects to the distal urinary tract (male urethra)
Describe blood flow to the penis during the flaccid state
blood flow minimal d/t vasoconstriction of vasculature
What are the 3 erectile bodies of the penis?
2 corpora cavernosa, 1 corpus spongiosum
–>anastomosing network of vascular spaces and loose CT
What do parasymp neurons innervating SM of penis release during erection?
NO
–>increases cGMP–> decreases intracellular Ca2+ so vasculature relaxes–> flow of blood into penis for engorgement and erection
How is venous drainage reduced during erection?
engorged tissue d/t vasodilation presses veins against noncompliant outer fascia
What does somatic stimulation do during erection?
increases contraction of muscles at base of penis to further promote erection
What neuro control is the movement of semen under?
sympathetic
–>closes internal sphincter of bladder to prevent retrograde flow via contraction of vas deferens SM
What is destroyed in a prostatectomy that results in retrograde ejaculation?
internal sphincter of bladder
What causes ejaculation of sperm?
rhythmic contraction of bulbospongiosus and ischiocavernous muscles that surround base of penis
–>innervated by somatic motor nerves
What occurs during capacitation?
uterine and fallopian tubes wash away inhibitory factors
loss of cholesterol @ head of acrosome makes it weaker
membrane of sperm more permeable to calcium–>increases motility
What is the fxn of hyaluronidase in the acrosome of sperm?
depolymerizes polymers that hold ovarian granulosa cells together
–>digest proteins in structural elements of tissue cells that adhere to ovum
What does testosterone deficiency in the 2-3 month of gestation lead to?
ambiguity in male genitalia
–>male pseudohermaphrodism
What does testosterone deficiency in the 3rd trimester of pregnancy lead to?
cryptorchidism, micropenis
What does testosterone deficiency in puberty lead to?
poor secondary sexual development, overall eunuchoid features
–>persistence of prepubertal characteristics (typical of opposite sex)
What does testosterone deficiency post-puberty lead to?
decreased libido, erectile dysfunction, decreased facial and body hair growth, low energy, infertility
What occurs when GnRH neurons fail to migrate into the hypothalamus during embryo development?
Kallman’s syndrome
What is characterized by delayed or absent puberty and impaired sense of smell?
Kallman’s syndrome
–>form of hypogonadotropic hypogonadism
m>f
What is Klinefelter syndrome
seminiferous tubular dysgenesis (extra X)
–>phenotypically male because of Y chromosome
@ puberty, failure to induce normal testicular growth and spermatogenesis
low androgen production–> primary hypogonadism
infertility d/t destroying of seminiferous tubules
How to classify primary hypogonadism?
decreased testosterone
increased LH
What are the testosterone/LH levels in Klinefelter’s syndrome?
decreased testosterone
increased LH
What are the testosterone/LH levels in Kallmann’s syndrome?
- decreased GnRH
- decreased or nml LH
- decreased testosterone
What can androgen receptor antagonist be used to treat?
prostate cancer
What do tumors of testis produce large amounts of?
testosterone
What do germinal epithelial tumors produce?
don’t produce any hormones
What happens to androgen production, LH and FSH levels as men age?
gonadal sensitivity to LH decreases
androgen production drops
FSH>LH
What does hyperprolactinemia suppress?
FSH and LH secretion
