VPHY EXAM 3

hormone released from hypothalamus

GnRH

hormone released from anterior pituitary

FSH and LH

what type of receptors do FSH and LH use?

integral membrane proteins

what type of receptors do estrogens and androgens use?

intracellular receptors

flow of hormones from HPG axis

• secrete GnRH

• GnRH in hypothalamo-pituitary portal

• released to anterior pituitary

• releases FSH and LH

• FSH and LH to gonads to secrete sex hormones

• sex hormones to reproductive tract and the organs

what are the basic feedback patterns in the HPG axis system?

• negative feedback from sex hormones to the hypothalamus and anterior pituitary

LH impacts on male cells

leydig cells to produce testosterone

FSH impacts on male cells

sertoli cells to produce androgen binding proteins and inhibin

LH impacts on female cells

theca cells produce progesterone and androgens

FSH impacts on female cells

granulosa cells convert androgens into estrogens and inhibin

what sex hormones cause a negative feedback on the anterior pituitary?

progesterone and testosterone

what causes a negative feedback on FSH?

inhibin from granulosa and sertoli cells

androgen binding proteins

• releases in testes

• allow testosterone to bind which keeps concentrations high

androgens

• sex hormones in highest percentage in males

• convert into testosterone and DHT by 5-a-reductase

• DHT is the most physiologically active

estrogens

• converted from androgens→ testosterone→ estrogens by aromatase

• estrone and estradiol

• estradiol is 20x more physiologically active

fertility

ability to conceive children

infertility

• not being able to achieve pregnancy after 1 year of having regulated unprotected intercourse

• or after 6 months if older than 35 years old

fertility in men across life span

• fertility starts at puberty

• remains fairly constant through life

• slight decrease with age

fertility in females over life span

• fertility starts at puberty

• cycles throughout life depending on ovulation cycle

• sharp drop off at 60

3 ways to measure fertility

1. sperm quality and quantity

2. regularity of menstrual and ovarian cycle

3. possibility for implantation in uterus and maintenance of pregnancy over gestation

factors impacting fertility: sex chromosomes and genes

• y-chromosome has sry gene that encodes a transcription factor that directs formation of male sex organs overriding female development

• primordial gonads to fetal testes

• ex: tuner syndrome with one X chromosome → female

• ex: klinefelter syndrome: XXY but since Y chromosome is present SRY gene is present, but will have weaker secondary male characteristics, but can have hormonal therapy to enhance

factors impacting fertility: hormonal

HPG axis secretes GnRH from hypothalamus which releases FSH and LH to anterior pituitary to gonads

factors impacting sex determination

1. sex chromosomes

2. genes

3. hormones

4. sex organs

5. secondary sec characteristics

sex determination pathway for males

• SRY present which interacts with DAX1 inhibiting it

• this allows SRY to upregulate the expression of SOX9 and SF1

• they bind to anti-mullerian hormone (AMH)

• ultimately inhibiting development of female reproductive tract

• developing wolffian tubes

sex determination pathway for females

• NO SRY gene present to inhibit DAX1

• therefore DAX1 suppresses the expression of SOX9 and SF1

• NO binding to AMH

• ultimately allows development of female reproductive tract, mullerian tubes

XX male

X chromosome picked up SRY gene so able to override default female pathway

XY female

y-chromosome lost SRY gene so not able to override default female development

male reproductive anatomy and pathway

• sperm produced in seminiferous tubules in the testes

• collect in reet testis and exit to ductules

• to epididymis

• to ductus deferens

• travels over the bladder to posterior side to join with seminal vesicle

• joins to the ejaculatory duct in prostate gland that release nutrients for maturation

• ejaculatory duct to urethra to exit through penis

female reproductive anatomy

• uterus open to pelvic floor cavity

• ovary not directly connected to uterus

• oocytes in primordial follicles until puberty

• once puberty occurs transition into primary follicles

• to dominant follicles

• one dominant follicle ovulates and the other not ovulated turn into corpus luteum

• each month after puberty 10-25 preantral begin to form

• meiosis I is paused before meiosis II and completes with fertilization

• preantral takes around 9-12 months to develop into dominant cell

external sexual differences

• genital tubercule: glands of penis or clitoris

• labioscrotal folds: scrotum or labia majora

spermatogenesis

• begins are puberty

• two meiotic divisions of one spermtogonium turning into 4 sperm

• continuous

• time to produce to ejaculation is 42-76 days

• typical concentration >20 million

• <15 million→ infertility

• daily spent production of 150-275 million→ lots of storage

• Leydig cells produce testosterone but mediated by sertoli cells

What is the effect of ABP on T?

once testosterone is bound to ABP it is less lipophilic which means it stays stuck so higher amounts in testes

testosterone effects before birth

• masculine reproductive tract

• precursor for DHT→ descent of testes into scrotum

• DHT has a higher affinity so more physiologically active

testosterone effects on sex-specific tissues

• spermatogenesis and oogenesis

• promote growth and maturation of reproduction at birth

• precursor for all estrogens

• maintain reproductive tract at adulthood

• sex drive

• feedback on LH and FSH

testosterone effects in secondary sex characteristics

• male hair growth pattern

• deepening of voice, thickening of vocal cords

• protein anabolic effects

• muscle growth

• bone growth at puberty

• aggressive behavior

testosterone clinical trial

• NES/T

• nesterone suppresses gonadotropins LH and FSH

• gel that is applied to upper torso

• steroids are easily absorbed through skin

• T added for sex drive

pathway for ejaculation

1. seminiferous tubules

2. epididymis

3. ductus deferens

4. ejaculatory duct

5. urethra

condoms

• barrier to lessen STIs

• risk of breakage without lube

• risk of slippage and leaking if not properly fitted

• 87% effectiveness

vasectomy

• minimally invasive surgery with localized anesthesia

• “reversible” suture or cut to ductus deferens ~70%

• 99% effective

spermicide

• nonoxyl-9

• creams or gels

• break down acrosome which is the enzyme membrane used to break down the stem cells of oocyte to fertilize

• breakdown causes the sperm to lose functionality

• use in combination with other contraceptives

copper IUD

• ~10 years

• inhibits motility and acrosomal activation

• in uterine cavity

• string for insertion

• can be removed

• not protecting against STIs

• 97-99%

oogenesis

• 1-2 million primary oocytes arrest at birth

• ~300,000 primary oocytes at puberty

• only 400-500 ovulate

• fertilization completes meiosis

• secondary oocyte nucleus fuse with haploid sperm nucleus

• polar bodies eliminate one half of the diploid chromosome leaving a haploid cell

follicular phase feedbacks

estradiol has a negative feedback on FSH and LH in the anterior pituitary and GnRH from the hypothalamus

midcycle feedback

estradiol has a positive feedback on FSH and LH from the anterior pituitary and GnRH from the hypothalamus

luteal phase feedback

progesterone has a negative feedback on FSH and LH from anterior pituitary and GnRH from the hypothalamus

what phase is estradiol the most dominant?

follicular and midcycle

what phase is progesterone the most dominant?

luteal phase

early to mid follicular phase

• days 1-14

• low levels of estrogen have a negative feedback on GnRH, FSH, and LH

• estrogen that is produced has a positive feedback on more estrogen secretion

• AMH prevents more follicles from forming

• LH and FSH at its lowest levels

• estrogen starts to rise and progesterone slightly

late follicular phase and ovulation

• Day 15

• increase in estrogen and rising progesterone cause LH surge→ triggers ovulation

• FSH as well but limited because of inhibin

• one or more follicles fully develop into a released oocyte

• now a positive feedback on GnRH, FSH, and LH

luteal phase

• days 16-28

• combined estrogen and progesterone shut off FSH and LH

• estrogen and progesterone levels fall when the corpus luteum degenerates

• gonadotropins start follicular development for new cycle

• corpus luteum secrete progesterone and estrogen levels of FSH and LH decline

• dominant hormone is progesterone

hormonal control: early follicular phase

• theca cells in follicles produce progesterones and androgens by stimulation from LH

• androgens are taken up by granulosa cells by stimulation from FSH to produce estrogen via aromatase

• estrogen levels are starting to inc→ small positive feedback on granulosa cells to produce more estrogen

• BUT overall negative feedback on anterior pituitary to limit FSH and LH

hormonal control: late follicular phase to ovulation

• inhibin now starts being released from granulosa cells that has a negative feedback on FSH

• right before ovulation there is a high estrogen and rising progesterone enhance pituitary response to GnRH

• now positive feedback causes ovulation LH surge

• 16-24hrs after LH surge is when ovulation occurs

• body temp also increases due to progesterone

hormonal control: mid luteal phase

• corpus luteum formed from other follicular cells

• estrogen and progesterone (highest)

• inhibin has a strong negative feedback on GnRH, FSH, LH

• prevents ovaries from ovulating another oocyte

hormonal control: late luteal phase

• without pregnancy the corpus luteum degenerates

• levels of progesterone, estrogen, and inhibin fall to the lowest levels

• no negative feedback present allowing the hypothalamus to release GnRH→ FSH and LH to restart the cycle

menstrual phase

• days 1-5

• lack of ovarian hormones and shed

proliferative phase

• days 6-14

• estrogen increase by follicles

• estrogen binds to endometrium

• endometrium thickens

• progesterone receptors increase in the cells

secretory phase

• days 15-28

• after ovulation

• during luteal phase

• primarily progesterone so receptors respond to progesterone to full maturity

• inhibit muscle contraction to not shed potential oocyte

• inc blood vessels

• secrete nutrients for sperm and embryo

• form cervicle plug

hormonal birth control

• chemicals: progestin (synthetic progesterone), estrogen

• delivery: pill, shot, implant, lube

• prevent ovulation

pills

• hormones regulate ovarian cycle

• estrogen and progestin

• pill taken daily to prevent maturation and release of oocyte

• stop/reduce ovulation

• thicken cervical mucus

• thin uterine lining

• 93% effective

emergency contraceptive

• levonorgestral: class of progestin

• binds to progesterone and androgen receptors

• slow GnRH and suppress LH surge

• most effective within 24hrs (94%) and up to 3 days (58%)

• ulipristal acetate: prescription only

• works in similar way but can delay ovulation even if LH surge has occured

• 24hrs 98% and 3 days (85%)

shot

• contains progestin

• every 3 months

• stops ovulation

• 94%

implant

• in bicep

• steady release of progestin

• lasts 5 years

• 99%

hormonal iud

• progestin

• 3-8 years

• 99%

benefits beyond contraception

• improved cycle control

• relief from menstrual symptoms: bleeding, cramps

• less acne and hair growth

• bone health

• prevent ovarian endometrial and colorectal cancer

  • 1/3 of ovarian and 1/5 colorectal

risks of contraceptives

• no correlation to weight gain, fertility, or depression

• once discontinued ~2 week period before ovulating

• 0.013% risk of breast cancer and even lower if younger than 35

• risk normalizes after 5 years off contraceptive

fertility awareness

• tracking menstrual cycle

• 77% of cycles are not identical so not very effective

permanent contraception

• bilateral tubal ligation

• clip, cauterize, or ring fallopian tubes

• complete removal of uterine tubes

• 98-100%

what type of response is an erection?

parasympathetic response

ejaculation

• release of semen

• sympathetic release

• may or may not accompany an orgasm

fertilization

• secondary oocyte only capable of being fertilized 12-24 hours after ovulation

• capacitation of sperm

• ejaculated sperm are infertile until inside of the female after 7-10 hours

• fallopian tube is site of fertilization

• most fertilization occurs within 24hours after ovulation

• sperm can be stored fro 6-10 days

• blastocyte implants 6-10 days after fertilization

early development

• cleavage of zygote 36 hours

• 16 cell stage 50-60 hours

• blastocyst D4

• inner cell mass → embryo → fetus after week 8

• trophoblasts → form fetal placenta

• implantation in uterine wall D 8-9

• estrogen and progesterone increase continuously from the corpus luteum

• hCG secreted from trophoblast cells as implantation start

• allows persistence of corpus luteum and prevents menstrual cycle

superior vena cava

inferior vena cava

right pulmonary artery

right pulmonary veins

right atrium

tricuspid/av valve

right ventricle

pulmonary/semilunar valve

left pulmonary artery

aorta

left pulmonary veins

left atrium

biscuspid/av valve

left ventricle

aortic/semilunar valve

atria

receiving chambers

ventricles

pumping chambers

atria to ventricle valves (av)

right: tricuspid

left: bicuspid

ventricles to vessel valves (semilunar)

right: pulmonary valve

left: aortic valve

blood flow series of events

• blood enters from the inferior and superior vena cava

• into the right atrium

• passes through the tricuspid valve into the right ventricle

• through the pulmonary valve

• into right and left pulmonary arteries to go to the lungs

• oxygenated blood enters through the right and left pulmonary veins

• to left atrium

• through the bicuspid valves into the left ventricle

• through the aortic valve

• aorta to circulation

what is blood flow?

change in pressure/resistance

types of cardiac muscles

1. myocardial contractile cells: cardiomyocytes

2. myocardial conducting cells: auto-rhymicity, self-initiating AP, spreads cell to cell, triggers smooth muscle contraction

cardiac contraction series of events

1. atrial and ventricular diastole

2. atrial systole

3. isovolumetric ventricular contraction

4. ventricular systole

5. isovolumetric ventricular relaxation

atrial and ventricular diastole

• both tricuspid and bicuspid valves are open

atrial systole

• blood flows into atria

• av valves (tricuspid and bicuspid) are open

• atria contract which decreases volume increasing pressure which pushes blood from the heart into the ventricles

• semilunar valves are CLOSED

isovolumetric ventricular contraction

• EDV: end diastolic volume, amount of blood before ventricles contract

• av valves and semilunar valves are CLOSED

ventricular systole

• ventricles contract

• the volume is decreasing which increases pressure which will burst open the semilunar (pulmonary and aortic) valves pushing blood into the aorta and pulmonary trunk

• av valves CLOSED to prevent any flow back

isovolumetric ventricular relaxation

• ESV: end systolic volume, amount of blood in ventricles after systole

• all valves are closed