Physpharm week 8&9

cell membrane

made of phospholipid bilayer, with proteins embedded into membrane
lipid soluble molecules can pass through

non charged molecule example

steroid hormones, pass through the lipid bilayer to interact with specific receptors
(steroid cases the receptor is located in cell, either in cytoplasm or nucleus)

macromolecules example

peptide hormones
cannot go through lipid bilayer, must interact with specific receptor to transmit messages to cell

ions

carry a charge, cannot pass through lipid bilayer and have to rely on protein channels in membrane to move across

image of molecules that can pass through and can not

hormones

chemical molecules that have different properties
there are lipophilic steroid hormones, hydrophilic peptide hormones (bind to membrane-bound receptor)

how does the endocrine system help maintain homeostasis

hormone expression can regulate many body functions, primarily controlled by negative feedback loops
the endocrine system acts as the negative feedback loop
hormones can be effectors and controlled variables
communication is key to maintain homeostasis

kind of communication in body: long distance communication

nervous system and endocrine system

kind of communication in the body: short distance

autocrine and paracrine

how does a neurotransmitter differ from a hormone and neurohormone

short distance vs long distance

neurohormone

a chemical signal secreted into the blood from a neuron to act on a distant tissue
the brain releases all sorts of hormones, some hormones are released by glands, while others by neuronal tissue
ex. ADH (antidiuretic hormone)

how does hormone signalling work?

receptor-ligand specificity

hormones are released to entire body, how are their effects controlled?

1. hormones are released into the blood stream
2. hormones circulate throughout the body
3. hormones will only bind to their specific receptors
4. only target cells will express that receptor

examples of endocrine glands and associated hormones

pineal gland - melatonin
hypothalamus - hormones that control the pituitary
pituitary gland - oxytocin, ADH
parathyroid gland - parathyroid hormone
thyroid gland - thyroid hormones (T3 and T4), calcitonin
adrenal gland - aldosterone, epinephrine, cortisol, androgens (DHEA)

endocrine glands

protein hormones and how properties differ from other hormones

hormone example: hormones from the hypothalamus and the pituitary, pancreas
precursor: amino acids
location of receptor: membrane bound
time before onset of action: fast acting, short lived

steroid hormones and how their properties differ from one another

hormone example: estrogen, testosterone, cortisol
precursor: cholesterol
solubility: lipophilic, bound to a protein
location of receptor: intracellular
time before onset of action: slow acting long lived

amine hormones and how their properties differ from one another

hormone example: thyroid hormone, epinephrine
precursor: tyrosine
solubility: some are lipophilic and bound to protein, some are hydrophilic and circulate freely
location of receptor: lipophilic = intracellular, hydrophilic = membrane bound receptor
time before onset of action: lipophilic - slow acting, hydrophilic - fast acting

how do hormones exert their activity on the target cell

membrane receptors: the cell will respond by activating or changing pre-exisiting proteins in the cytoplasm
cytoplasmic or nuclear receptors: the cell will respond by transcribing the DNA to make new mRNA and build proteins
Protein hormones: through secondary messengers
steroid hormones: through new gene transcription and protein production

receptors and hormones: second messenger systems: cAMP

1. non-steroid hormone (First messenger)
2. receptor protein attaches to activated enzyme
3. ATP cycles through to cAMP which is second messenger
4. effect on cellular function, such as glycogen breakdown

receptors and hormones: second messenger systems: tyrosine kinase

inactive monomers in extracellular fluid
goes through dimerization
ATP turned into ADP; leads to phosphorylation ADP on the bottom ends of proteins in cytoplasm
activation after, leads to active relay protein

receptors and hormones: steroid hormone receptor action in the cell

1. lipid-soluble hormone diffuses through plasma membrane
2. hormone binds with receptor in cytoplasm, forming a receptor-hormone complex
3. receptor-hormone complex enters the nucleus and triggers gene transcription
4. transcribed mRNA is translated into proteins after cell activity

receptor and hormones: Second messenger systems: GPCR and ion channels

ion channel and g-protein and receptor next to each other
receptor binds to hormone
when bound ion channel opens from g-protein moving bottom part
ions flow throughwh

what does hypothalamus regulate

body temperature
water balance
energy production
thirst
hunger
sexual behaviour

hormone properties and how they affect receptor interactions

hormone binds to specific receptor, receptor goes to target cell which elicits a cellular response

how does the hypothalamus regulate hormone release in the posterior pituitary

a. neuronal tissue
b. regulates kidney, breast tissue, uterus, human behaviour
c. hypothalamus to the posterior pituitary
d. hypothalamic hypophyseal tract

how does the hypothalamus regulate hormone release in the anterior pituitary

a. epithelial cells
b. affects breast tissue, thyroid, adrenal, gonad, various tissues
c. hypothalamus to anterior pituitary
d. hypothalamic hypophyseal portal system

relationship between hypothalamus, anterior pituitary and posterior pituitary gland

hypothalamus to anterior pituitary
hypothalamic hypophyseal portal system

hypothalamus to the posterior pituitary
hypothalamic hypophyseal tract

what hormones are released from the posterior pitutary and what effects do they have on the body?

the hypothalamus is connected to the posterior via the hypothalamic-hypophyseal tract
hormones:
a. antidiuretic hormone (ADH)
- peptide neurohormone
function: promotes water reabsorption in kidneys

b. oxytocin
- peptide neurohormone
function: promotes uterine contractions and milk excretion, makes you feel happy/comforted

hypothalamus and the posterior pituitary

release of ADH
- dehydration
- hyperosmolarity: increased osmolarity in extracellular fluid

inhibition of ADH:
- over hydration
- hyposmoloarity: decreased osmolarity in the extracellular fluid
- alcohol
- high blood pressure

what is diabetes insipidus

insufficent ADH, or ADH activation in the kidney

what causes diabetes insipidus

brain tumour
brain surgery
brain injury

what are symptoms of diabetes insipidus

producing lots of urine
urine is very dilute
dehydration
sensations of thirst

hormone replacement theory for diabetes insipidus

replace the hormone ADH
drug is called desmopressin
its a small peptide molecule and acts on the kidneys
can be administered through a pill, injection or a nasal spray

oxytocin and positive feedback loop

oxytocin causes the uterine muscles to contract
this pushes baby down harder to be delivered
nerve impulses sent back to brain that causes more oxytocin released

what are parts of anterior pituitary

hypothalamus
hypothalamic-hypopseal portal system
endocrine cells of the anterior pituitary

hormones of the hypothalamus and the anterior pituitary

chart 2 hormones of hypothalamus and anterior with target tissues

role of hypothalamus

links the nervous system to the endocrine system, regulates the pituitary gland

how does the hypothalamus regulate hormone release in the posterior pituitary

hypothalamic-hypopseal tract

how does the hypothalamus regulate hormone release in the anterior pituitary

hypothalamic-hypopseal portal system

What hormones are released from the posterior pituitary and what effects do they have on the body?

ADH (water balance) and Oxytocin (happy hormones, and reproduction)

What is an example of a pharmacological therapeutic for hormone deficiency?

hormone replacement therapy

reproductive endocrinology

ultimate purpose is to produce a cell (gamete) that can be combined with another cell to create a new organism

chromosomes

made up of long strands of DNA and contain genetic material that makes up an organism
they form an X shape, one half is the paternal (sperm) contribution and other is maternal (oocyte) contribution

sister chromatids

half of the chromosome is replicated and it is connected with its own copy to make sister chromatids

diploid

refers to the number of distinct chromosomes, 23 chromosomes come from sperm and other 23 come from oocyte, together forms a diploid cell with 46 chromosomes

haploid

refers to the number of distinct chromosomes but only half are present gives half of DNA to daughter cell and other half to different daughter cell

gametes

haploid cells involved in fertilization
they are made in the gonads of the parent organism

germ line cells

cells that give rise to the gametes
these cells will eventually become gametes through the process of meiosis
they reside in the testes or the ovaries

meiosis

the process through which a diploid cell becomes a haploid gamete to be used in fertilization and create a new organism
the phases happen twice in meiosis

interphase

cell replicates DNA, 46 distinct chromosomes, now has 2 copies of each chromosomes and each chromosome has a sister chromatid

prophase I

homologous pairs of sister chromatids for a tetrad and exchange DNA in a crossing over event
swap certain sections of DNA

metaphase I

sister chromatids form a line in the middle of the cell and spindle fibres connect them
homologous pairs are now separated from each other, the resulting daughter cells will have 23 distinct chromosomes that each have sister chromatid and go from 2N to N

anaphase I

sister chromatids are pulled away from their homologous pairs to opposite sides of the cell

telophase I and cytokinesis

cell membrane pinches in the middle to create 2 daughter cells
one that has one set of sister chromatids and the other has other set
these 2 daughter cells have a DNA compliment of N
each chromosome has a sister, it still has 46 chromosomes but only 23 distinct
2 daughter cells need to undergo meiosis II

prophase II

chromatin clumping
these chromosomes condense in each daughter cell and a new set of spindle fibers form
the chromatids move to line up in centre of cell

metaphase II

spindle fibers attach to each of the sister chromatids to prepare to seperate them apart

anaphase II

sister chromatids are seperated into opposite sides of the cell

telephase II

creates 4 different sex cells
each daughter cell now splits into 2 new daughter cells, forming 4 genetically distinct cells
these cells have 23 chromosomes, or a DNA compliment of N

uterer

connects kidney to bladder

bladder

stores urine and is connected to the uterer through a tube that runs through the prostate

seminal vesicle

contributes a large amount of fluid to the semen during ejaculation

prostate

the gland secretes enzymes and fluid to help neutralize the acidic environment of the urethra, and the vagina
without fluids the prostate gland to neutralize acidic environment of vagina, sperm would die

vans deferens

tube connecting testes to uterer that conducts sperm during ejaculation

ejaculatory duct

drains into the urethra

Bulbourethral gland

releases a neutralizing and lubricating fluid into the uterer prior to ejaculation
the fluid is alkaline and is necessary to neutralize the acidic environment of the urethra that occurs after urination
prior to ejaculation

urethra

conducts both urine and sperm to the penis and out of body

penis

largely of erectile tissue and acts as the conduit for sperm transfer during copulation, conduit for urination

testes

site of sperm production
produce and secrete 2 hormones, testosterone and inhibin in response to gonadotropins from the anterior pituitary

epididymis

site of sperm maturation and storage

fimbrea

capture the oocyte after its released by the ovary at ovulation
the fimbrea are finger like projections that sweep the oocyte into the fallopian tube

uterine (fallopian) tube

where sperm and oocyte will meet and fertilization will occur
uterine tube contains cilia that help move the oocyte or embryo along the uterine tube of the uterus
movement of the uterine tube is regulated in part by progesterone

ovary

site of developing female gamete
responsive to FSH and LH and it secretes estrogen and progesterone
the ovary will release the oocyte during ovulation

uterus

muscular organ that accommodate and maintains a pregnancy
site of normal embryo implantation into the endometrium
development of the endometrium is regulated by estrogen, while the maturation of the endometrium is regulated by progesterone

cervix

forms the connection between the vaginal canal and the uterus
secretes mucus that varies during the menstrual cycle from thin (facilitate sperm entry) to thick (prevent sperm entry)
higher estrogen levels causes cervical mucus to be thinner, while higher progesterone levels cause the cervical mucus to be thicker

vagina

receives the penis and sperm during copulation
allows for the discharge of fluid during menstruation, and the birth of the baby

spermatocytes

adult stem cell
developing sperm cells

sertoli cells

support and regulate spermatogenesis
blood testes barrier
produce inhibin

leydig cells

produce testosterone
located in the space between seminiferous tubules

how is sperm developed (spermatogenesis)

Meiosis occurs in the testes to produce haploid gametes
a. Spermatozoa
b. Spermatids
c. 2 degree spermatocytes
d. 1 degree spermatocytes
e. Spermatogonia

features of mature sperm

head
- nucleus
- acrosome

tail
- neck
- middle piece
- principal piece
- end piece

how is sperm development regulated by hormones and negative feedback loops

FSH - inhibin
LH - testosterone

class of hormone - steroid, comes from cholesterol
hydrophobic
intracellular is where receptors located
transported into blood by albumin

what are the effects of testosterone on the body

muscle mass, lower voice, secondary hair growth, blood cell count
- growth of prostate
- secondary sex characteristics
- vocal changes
- red blood cell count
- anabolic reactions (muscle mass)

anti-GnRH - treatment for prostate cancer

- prevents the secretion of LH and FSH
- prevents secretion of testosterone from the testes
- prevents the growth of prostate

how are oocytes made (oogenesis)

oogonia - diploid stem cells of ovaries
begin meiosis I, stops at prophase
remains inactive in cortex of immature ovary until puberty
small number activated each month - recruited by FSH
only one continues through meiosis

how does gamete development differ between sperm and oocyte

what is folliculogeneis and how does it occur

folliculogenesis of the maturing oocyte
male: the cells that help sperm develop are part of the testes, they include Sertoli and Leydig cells

female: the cells that help the oocyte develop make up the follicle that surrounds the oocyte, they are called Theca and Granulosa cells

*look at week 9 lecture 1 slide 21*

what is the viability of gametes

oocytes
- usually fertilized within 12 hours of ovulation
- cannot be fertilized after 24 hours

spermatozoa
- viable for approximately 48 hours in female reproductive tract

what are the support cells in folliculogensis

Theca cells and Granulosa cells

what are the stages of the female reproductive cycle and how are they regulated by hormone

how are female hormones regulated

theca and granulose cells: produce sex steroids

how hormones are regulated using negative and positive feedback loops

what are the events that occur in the uterus during the reproductive cycle

how menopause occurs

loss of primary follicles means less estrogen
less estrogen mens levels are so low that we lose the negative feedback effect
FSH and LH levels rise dramatically, causing strange fluctuations in primary follicle recruitment, and estrogen levels
pituitary becomes exhausted, LH and FSH levels drop
cycle ends, and menopause is reached
begins to happen between 45-55

symptoms of menopause

hot flashes
loss of fertility
change in bone health
metabolic changes

what does sperm require to successfully locate the oocyte

armour/protection
food
a map
help from other sperm h

how much sperm is needed

ejaculate: 15 million/ml - 200 million/ml
reach the ovum: 50-100
fertilization: 1

what are the stages of early embryo development

zygote
4 cell stage
morula
blastocyst (day 5 post-fertilizatior)

overview of menstrual cycle