Physiology Flashcards
What hormones initiate puberty and how does this lead to the development of secondary sex characteristics
pulsatile secretion of GnRH -> pulsatile secretion of FSH and LH -> stimulates testosterone & estrogen (causes secondary sex characteristics)
Name 2 things that could delay the onset of puberty?
extreme stress or caloric deprivation
What is melatonin a natural inhibitor of? What would occur if the pineal gland was removed?
- melatonin inhibits GnRH
- if pineal gland was removed, early puberty would occur in children
What is most testosterone converted to when it reaches target tissues?
dihydrotestosterone (DHT)
What cells make the majority of testosterone and in what organ are they located?
Leydig cells of the testes
What does 17B-hydroxysteroid dehydrogenase do in the testes?
coverts androstenedione to testosterone
Name some tissues where DHT is the active androgen (4)
prostate gland, external genitalia of male fetus, skin, liver
What enzyme converts testosterone to DHT in the peripheral tissues?
5a-reductase
What is the majority of circulating testosterone bound to?
sex hormone-binding globulin (SHBG) and albumin
What binds to testoserone as it is concentrated in the lumen of seminiferous tubules?
antigen binding protein (ABP)
Where does estrogen come from in males?
- some produced by sertoli cells
- aromatase converts testosterone to estrogen
- liver (accounts for 80% of male estrogen)
What is the RLS of testosterone synthesis? What stimulates this step?
- cholesterol -> pregnenolone by cholesterol desomolase (P450scc)
- stimulated by LH (acts on Leydig cells)
What type of receptor are androgen receptors (AR)?
nuclear receptors
Which has a higher affinity for the AR - testosterone or DHT?
DHT
What is the biologically active form of testosterone in the body?
free unbound testosterone (2%)
What actions do testosterone have during fetal development?
- fetal differentiation into internal and external genital organs
- cause descent of testes into scrotum towards last few months of pregnancy
Name 7 actions of testosterone during puberty?
- increased muscle mass
- growth spurt
- closure of epiphyseal plates
- penile growth
- deepening of voice
- spermatogenesis
- libido
Name 4 specific actions of DHT
- fetal differentiation of male external genitalia
- male hair distribution and baldness
- sebaceous gland activity
- prostatic growth
What can be used as a tx for BPH and male patter baldness in males?
5a- reductase inhibitors (inhibits DHT production)
Name some anabolic actions of androgens
- stimulates EPO
- nitrogen retention
- stimulates linear body growth
What are the intracellular mechanisms of LH on Leydig cells?
Bind to LH receptor -> Gs pathway -> protein synthesis (produces enzymes involved in testosterone synthesis)
What hormones do the Leydig cells and Sertoli cells respond to?
- Leydig: LH
- Sertoli: testosterone and FSH
What are the intracellular mechanisms of FSH and testosterone on Sertoli cells
- FSH: binds to FHS receptor -> Gs pathway -> protein synthesis (ABP, inhibin, and aromatase)
- Testosterone: converted into estradiol by aromatase or enters lumen w/ developing spermatogonia
What is the function of inhibin in both males and females?
inhibits FSH release
Name 3 supporting functions of Sertoli cells
- blood-testis barrier
- phagocytosis
- supply nutrients to sperm from blood
Name 3 exocrine functions of Sertoli cells
- production of fluid
- production of ABP
- determination of sperm release from seminiferous tubules
Name 4 endocrine functions of Sertoli cells
- expression of ABP, testosterone, and FSH receptor
- production of AMH
- aromatization of testosterone to estradiol
- production of inhibin
How long does the process of spermatogenesis take?
between 64-72 days
What is spermatocytogenesis and when does it begin? End result?
- mitotic division phase - begins at puberty
- results in primary spermatocytes
What does the meiosis phase of spermatogenesis result in?
primary spermatocytes -> secondary spermatocytes -> spermatids
What is spermiogenesis?
maturation of spermatids into mature spermatozoa
What affect does GH have on spermatogenesis?
- controls background metabolic function of testes
- promotes early division of sperm themselves
What is the effect of exogenous testosterone in peripheral tissues and testes?
- peripherally more free testosterone (anabolic effects)
- increased negative feedback on LH -> less testosterone produced in testes -> decrease in spermatogenesis
What is decapacitation?
addition of molecules to the membranes of sperm to prevent acrosomal reaction before contact w/ egg
What is the purpose of fructose in semen? What produces it?
- main energy source for sperm
- seminal vesicles
What is the purpose of prostaglandins in semen (2)? what produces it?
- react w/ cervical mucus and makes it thinner to be more receptive to sperm
- causes backward contraction of uterus/fallopian tubes to move sperm towards ovaries
- seminal vesicles
What is the final pH of semen?
7.5 - alkaline
What is the maximal life span of sperm after ejaculation?
24-48 hours
What number of sperm is considered to be infertile?
< 20 million
In what way does the nervous system initiate an erection?
parasympathetic nerves innervating vascular smooth muscle release NO
How does NO cause vasodilation?
stimulates guanylyl cyclase -> GTP to cGMP -> decreased intracellular Ca -> relaxation of smooth muscle -> blood flow increases
What converts cGMP -> GMP in the penis at the end of an erection?
Type 5 phosphodiesterase
What is the MOA of viagra?
Type 5 PDE inhibitor (helps maintain erection)
Under what type of control is emission?
sympathetic control
What effect does smooth muscle contractions of the vas deferens have (2)? Why is this important?
- movement of sperm to the ejaculatory duct
- closure of the internal urethral sphincter (prevents back flow semen into the bladder)
What muscles contract during ejaculation? What are they innervated by?
- bulbospongiosus M. and ischiovacernous M.
- innervated by somatic motor nerves
What changes occur in the female tract that allow for capacitation of sperm?
- wash away inhibitory factors
- loss of cholesterol built up on head of sperm
- membrane more permeable to Ca -> increased motility
Explain the effects of testosterone deficiency at each of the following time periods: 2-3 months gestation, 3rd trimester of pregnancy, puberty, post-puberty
- 2-3 months gestation: ambiguity of male genitalia
- 3rd trimester: cryptorchidism and micropenis
- puberty: poor secondary sex characteristics and eunuchoid features
- post-puberty: erectile dysfunction, decreased libido, and infertility
What is eunuchoidism?
persistence of prepubertal characteristics and often presence of characteristics typical of opposite sex
What is Kallmann’s syndrome? Sxs?
- genetic disorder where GnRH neurons fail to migrate to hypothalamus during development (tertiary hypogonadism)
- delayed/absence of puberty and impaired sense of smell
What is Klinefelter syndrome and what is seen with it?
- 47, XXY
- appear male at birth
- failure to induce testicular growth/spermatogenesis at puberty
- androgen production usually low but gonadotropins are high (primary hypogonadism)
- seminiferous tubules are destroyed -> infertility
Give an example of primary, secondary, and tertiary male hypogonadism
- primary: klinefelter syndrome (decreased testosterone production)
- secondary: pituitary dysfunction (decreased LH/FSH secretion)
- tertiary: Kallmann’s syndrome (decreased GnRH secretion)
What occurs as a result of decreased gonadal sensitivity to LH in males around the age of 40?
- increased serum levels of LH and FSH (FSH > LH)
- decreased testosterone production
- decreased bone formation, muscle mass, facial hair, appetite, and libido
What 3 layers of the oocyte does the sperm have to penetrate?
- cumulus cell matrix (corona radiata)
- zona pellucinda
- plasma membrane of oocyte
Around what day of the menstrual cycle does fertilization usually occur?
day 15-16
Which part of the uterine tube does fertilization generally occur? Which part of the uterus does implantation generally occur?
- fertilization in the ampulla of the uterine tube
- implantation in the posterior wall of the fundus of the uterus
Explain the purpose of decapacitation in the male?
cholesterol hardens the acrosome to prevent it from releasing its proteolytic enzymes in the male genitalia
What causes capacitation of sperm?
uterine/fallopian fluid washes away the inhibitor factors on the sperm (ex. cholesterol)
What changes occur in the sperm after capacitation occurs?
- membrane becomes permeable to extracellular Ca (increased tail movement and activation - preparation to release enzymes)
- gains ZP3 receptors
What is the cumulus cell matrix made of?
mainly hyaluronic acid
Describe the 3 glycoproteins that make up the zona pellucida
- ZP1: structural (crosslinks ZP2 and ZP3)
- ZP2: blocks polyspermy
- ZP3: initiates acrosome reaction
What specific proteolytic enzyme does the acrosome of sperm contain? Which layer does this break through?
hyaluronidase - breaks through cumulus cell matrix
Explain how ZP3 initiates acrosome reaction?
sperm w/ ZP3 receptor (from capacitation) bind to ZP3 in zona pellucida and release proteolytic enzymes to break apart structural components of zona pellucida
What occurs after the sperm break through the ZP3 layer of zona pellucida?
ZP3 receptor falls off and sperm can bind to ZP2 (prevents any more sperm from breaking through)
What is the sperm reservoir?
place in the isthmus of the uterine tube where sperm bind to epithelium to wait for oocyte to be released
What is the cortical reaction (3 steps)?
- initiated during fertilization
- release of granules to prevent polyspermy (ZP2 -> ZPf); hardens zona pellucida
- Ca stimulates completion of meiosis II
- egg activation (fusion of male and female pronuclei
Describe compaction and blastocele development in embryonic development
occurs w/ the morula (16 cell mass) around day 3 -> cells compact tightly to create outer trophoblast and inner cell mass (embryoblast) with blastocele space in between (due to Na)
What is blastocyst hatching?
blastocyst breaks free from hardened zona pellucida to continue growing (day 5)
What occurs if blastocyst hatching occurs too early?
blastocyst can attach early in the uterine tube (ectopic pregnancy)
What are the functions of hCG (3)?
- prevents involution of the corpus luteum which is producing progesterone and estrogen (prevents menstruation and maintains early pregnancy up to 10 weeks)
- stimulates trophoblast growth (via progesterone)
- stimulates placental growth
What 2 types of cells do trophoblasts develop into?
- cytotrophoblasts (supporting cells)
- synchitiotrophoblasts
Name 4 functions of synchitiotrophoblasts
- increased invasion of endometrium
- secrete hCG (high levels after week 10)
- secretes progesterone (week 10)
- phagocytosis and bidirectional placental transfer
What are the 3 steps of implantation?
apposition; attachement; invasion
What occurs in apposition during implantation?
contact between endometrium and trophoblasts; inner cell mass rotates to face endometrium
What occurs in attachment during implantation?
- trophoblasts adhere and surface proteins interact w/ epithelial cells
- initiates changes of endometrial stroma (decidualization - maternal reaction to implantation)
What occurs in invasion during implantation?
- degradation of endometrial epithelial cells
- trophoblast fusion and formation of syncytiotrophoblasts
What is added to endometrial stroma after decidualization? What hormone is involved in this process?
filled and glycogen filled decidual cells (endometrium -> decidua); through progesterone
What is the function of the decidua?
- involved in nutrient exchange w/ embryo
- protects embryo from maternal immune system
- controlled invasion of trophoblast (sticks to proper layer of uterus)
What develops in synchitiotrophoblasts around day 9?
lacunae (spaces filled w/ endometrial secretion and blood for nutrient transfer)
Describe the primary placental villi
proliferation of syncytiotrophblasts and cytotrophoblasts into lacunae
Describe the secondary placental villi
mesenchyme cells from extra embryonic mesoderm invade villi
Describe the secondary placental villi
mesenchymal cells from fetal blood vessels de novo
