Male Reproductive Physiology _ PV Flashcards
Gonads at first 5 weeks of gestational life
gonads are bipotential ( neither male or female)
Gestational week 6-7
testes begin to develop in genetic males
gestational week 9
ovaries begin to develop in genetic females
Gonadotropin secretion over lifetime
- childhood
- adult reproductive period
- senescence
- childhood: FSH>LH
- adult reproductive period: LH> FSH
- senescence: FSH>LH ( menopause= lack of negative feedback of LH/FSH secretion)
Secretion of GnRH
- how is it secreted
- if it doesn’t follow patter
PULSATILE secretion of GnRH=> PULSATILE secretion of FSH and LH => steroid, testosterone, estradiol => puberty is administered
if long-acting, chronic GnRH is administered=> puberty is not initiated
What can alter onset of puberty? (3)
- caloric deprivation
- extreme stress
- MELATONIN
- highest in childhood and declines in adults
- removal of pineal gland causes early puberty
List the anatomy of male reproductive tract (8)
- Testes
- Epididymis
- Scrotum
- Vas Deferens
- Seminal Vesicles
- Prostate Gland
- Seminiferous tubules
- Leydig Cells
Testes
- functions (2)
- secretion of testosterone
2. develop sperm (spermatogenesis)
Scrotum
- function
its lower temperature is essential for spermatogenesis
Epididymis
- function (2)
1) primary location for sperm maturation
2) storage of sperm
Vas Deferens
- function (2)
- provide another storage area for sperm (ampulla)
2. secretes fluid rich in citrate and fructose
Seminal vesicles
- function
secretes fluid rich in citrate, prostaglandins, and fibrinogen
Prostate gland
- function
secretes milky aqueous solution rich in citrate, calcium, and enzymes
seminiferous tubules
- describe components
epithelium formed by Sertoli cells
- spermatogonia: most immature germ cells, located near the periphery of tubules
- spermatozoa: mature germ cells, located near the lumen of the tubules
Leydig cells
interstitial cells that lie between tubules
What is the adult testis made up of
- 80% seminiferous tubules
- 20% CT interdispersed with leydig cells
Leydig cells
- function
synthesis and secretion of testosterone
Sertoli cells
- function (3)
- provide nutrients to differentiating sperm
- form tight junctions with each other, creating a barrier between testes and bloodstream
- secrete an aqueous fluid into lumen of seminiferous tubules
- helps to transport sperm through the tubules into epididymis
What does testes secrete? (3)
what is most abundant
- testosterone (MOST abundant)
- dihydrotestosterone
- androstenedione
What happens to testosterone in target tissues
T converts to DHT via 5 a reductase**
Testosterone
- describe (A LOT)
- where is it made
- what does is lack
- what does it have
major androgenic hormone
made in LEYDIG cells
In testes
- lack 21b hydroxylase & 11B hydroxylase => no glucocorticoid or minercorticoid
- HAVE 17B hydroxysteroid dehydrogenase
- converts androstenedione to testosterone
- end product of steroid synthesis => testosterone (NOT DHEA and androstenedione)
Testosterone
- binding proteins
- tissues ( think DHT)
in lumen of seminiferous tubules => bind to androgen-binding protein
in circulating testosterone=> bound to plasma protein and albumin ( Sex hormone-binding globulin)
DHT
- active androgen in prostate gland, external genitalia,skin, liver
Leydig Cells
- cholesterol production
makes cholesterol de novo - from the circulation through LDL and HDL
- stores cholesterol as cholesterol ester
(made by cholesterol HSL)
cholesterol ester -> free cholesterol via HSL
cholesterol transferred within mitochondrial membranes via steroidogenic acute regulatory protein ( StAR)
cholesterol converted to pregnenolone
Estrogen
- location
- function
in seminiferous tubules (SERTOLI CELLS)
T-> estradiol via aromatase
important role in spermatogenesis
much larger amounts of estrogen are formed from testosterone andandrostenediol in other tissues like liver
Mitochondrial pathway for testosterone synthesis
- RLS
Cytochrone P450 cleavage enzyme removes side chain from carbon at position cholesterol
RLS= desmolase
What stimulates the conversion of cholesterol to pregnenolone?
- how (2)
LH
- regulates overall rate of testosterone synthesis by Leydig cells
- increases affinity of P450cc enzyme for cholesterol
- stimulates synthesis of P450scc enzyme (LT action)
Testosterone production
- when does it begin
- what does it bind to
- target tissues
7-8 weeks of gestation
- bind to androgen receptor (AR)=> nuclear receptor
location in male:
- prostate, testis ( sertoli, leydig, and myoid cell), epididymis, seminal vesicles
non-reproductive tissue: neurons in CNS, anterior pituitary, thyroid skin, adrenal cortex, liver, kidney, bladder
location in female:
- ovary, mammary glands, uterus
DHT production
- bind
- enzyme
bind to androgen receptors, with greater affinity
plays important role in causing changes at puberty
deficiency of 5a reductase
results: ambiguos external genitalia
Testosterone
- binding protein proportions
- where is it excreted and how
60% circulating T bound to SHBG
38% circulating T bound to albumin
2% free T
Excreted via urine as urinary 17 ketosteroid (50%) or conjugated androgens/diol
Tissues that produce androgen
Adrenal gland
- cholesterol
- androstenedione
Peripheral tissues
- testosterone
- DHT
- estradiol
Fetal development
- with testosterone
- without testosterone
- disease
with testosterone= penis and scrotum
without testosterone= clitoris and vagina
fetal differentiation of internal male genital tract (epididymis, vas deferens, seminal vesicle)
- causes descent of testes into scrotum
Cryptorchidism: lack of descent
Testosterone at puberty
- characteristics (7)
- increased muscle mass
- pubertal growth spurt
- closure of epiphyseal plates
- growth of penis and seminal vesicles
- deepening of voice
- spermatogenesis
- libido
Specific actions of DHT (4)
- clinical correlation
- external male genetilia
- male hair distribution and male pattern baldness
- sebaceous gland activity
- growth of prostate
Baldness=> 5a reductase inhibitor for treatment
Andrgenic actions (4)
- regulation of differentiation of male internal and external genetilia in fetus
- stimulation of growth, development of 2 secual characteristics at puberty
- maintenance of reproductive tract and production of semen
- initiation and maintenance of spermatogenesis
anabolic actions of androgens (7)
- stimulation of erythropoietin synthesis (RBC)
- stimulation of sebaceous gland secretion
- control of protein anabolic effects ( nitrogen retention )
- stimulation of linear body growth , bone growth and closure of epiphyses
- stimulation of ABP synthesis
- maintenance of secretion of sex glands
- regulation of behavioral effects, libido
Benign prostatic
hyperplasia
- symptoms
symptoms
- urinary frequency
- nocturia
- difficulty initiating and maintaing a urinary strem
DHT concentration equal but MORE DHT receptors on prostate compared to normal
intracellular mechanism of testosterone
- Leydig cells
- sertoli cells
Leydig cells: LH receptor (cAMP-PKA pathway)
- results in steroidogenesis and testosterone production
- testosterone diffuses into seminiferous tubules and peripheral circulation
Sertoli cell: stimulated by testosterone and FSH (cAMP-PKA pathway_
- results in protein synthesis and production of inhibin (inhibits FSH release), ABP, aromatase, and other products
Sertoli cell and testosterone relationship
FSH stimulates the sertoli cells to secrete ABP into lumen of seminiferous tubules
- binding of testosterone in lumen provides a local testosterone supply for teh developing spermatogonia
aromatization of testosterone to estradiol 17B
Supportive function of sertoli cells (4)
- maintaining blood-testis barrier
- phagocytosis
- transfer of nutrients from blood to sperm ( transferrin, Fe, lactate)
- receptors for hormones and paracrine
exocrine functions of sertoli cells (3)
- production of fluid
- production of ABP
- determination of release of sperm from seminiferous tubules
Endocrine function of sertoli cells
- expression of ABP, T and FSH receptors
- production of AMH
- aromatization of testosterone to estradiol 17B
- production of inhibin to regulate FSH levels
Spermatogenesis
- occurs where?
- timeline
- cell type
- cells
occurs in seminiferous tubules
lined by stratified epithelium
Spermatogenic and Sertili cells
64 days
for supportive and nutrient function
Phases of spermatogenesis (3)
- mitotic division
- meiotic division
- spermogenesis
Mitotic division of spermatogenesis
- proliferative phase
- puberty=> mitotic cycles increase
- stem cell divide to produce daughter spermatogonia
- primary spermatocytes
Meiosis division of spermatogenesis
production of haploid gamete
- primary spermatocytes undergo two meiotic divisions
- two secondary spermatocytes each with haploid # of duplication crhomosomes
- then 2nd meiotic division=> producing two spermatids, each with a haploid number of unduplicated chromosomes
spermiogenesis (maturation)
spermatids undergo spermiogenesis and mature into spermatozoa
- nuclear and cytoplasmic changes to produce mature spermatozoa
- ends in testis with release of spermatozoa from sertoli cells
Hormones that stimulate spermatogenesis ( 5)
- luteinizing hormone
- follicle- stimulating hormone
- growth hormone
- testosterone
- estradiol
Luteinizing hormone
- secreted by
- function
secreted by anterior pituitary
stimulates leydig cells to secrete testosterone
Follicle- stimulating hormone
- secreted by
- function
secreted by anterior pituitary
stimulates sertoli cells to nurse and form sperm
w/o FSH= no spermiogenesis
Growth hormone
necessary for controlling background metabolic functions of the testes
promotes early division of sperm themselves
w/o it= pituitary dwarfs
(spermatogenesis is severely deficient)
Testosterone
- secreted by
- function
secreted by leydig cells
essential for growth and division of testicular germinal cells, which is beginning of sperm formation
estrogen
- location
- function
formed from the testosterone by the sertoli cells when they are stimulated by FSH
essential for spermatogenesis
Feedback regulation of spermatogenesis
- normal
- with exogenous testosterone
- negative feedback loop
2. increasing circulating T=> more negative feedback on LH/FSH=> decrease in spermatogenesis