PSL300 Term Test 2 (Weeks 5-8)

fed/fasted (anabolic/catabolic)

fed - absorptive, anabolic

- glycogenesis, lipogenesis, protein synthesis

fasted - 3-4 hours after eating, postabsorptive, catabolic

- glycogenolysis, lipolysis, protein degradation, gluconeogenesis (synthesis of glucose from glycerol or AAs)

- convert glucose to ATP (glycolysis), fatty acids to ATP (beta oxidation)

basal metabolic rate (BMR)

energy expenditure when resting, comfortable temperature, FASTED

insulin general

- peptide hormone

- anabolic

- dominant hormone of fed state

- promotes formation of glycogen, fat, protein (glycogenesis, lipogenesis, protein synthesis)

- inhibits glycogenolysis, gluconeogenesis, lipolysis, beta oxidation

- increase glucose transport into insulin-sensitive cells

- enhance cell proliferation

mechanism of insulin action

- insulin binds to tyrosine kinase receptor (1 TM)

- receptor phosphorylates insulin-receptor substrate (IRS)

- second messenger pathways

- membrane transport activity of GLUT4 modified

GLUT4 transporters in fasted/fed states

fasted - insulin doesn't bind as much to insulin receptor, GLUT4 stuck in vesicle

fed (high insulin/glucagon ratio) - insulin binds to receptor, signal transduction cascade, exocytosis of GLUT4, glucose enters cell

*GLUT4 found in muscle and adipose tissue

*movement of GLUT4 transporters confirmed with GFP

GLUT2 transporter in liver cells

insulin activates hexokinase, converts glucose to glucose-6-phosphate, maintain glucose concentration gradient

enhanced effect of intrajejunal glucose on plasma insulin

due to gastrointestinal GIP and GLP-1

- feedforward regulation, promote activity of insulin

GIP (gastric inhibitory peptide)

- stimulated by glucose/fatty acids/AA

- increase insulin, decrease gastric emptying

GLP-1 (glucagon-like peptide-1)

- stimulated by nutrients, parasympathetic activity

- increase insulin, decrease glucagon, increase beta cell growth, decrease gastric emptying, feeling of satiety

glucagon general

- secreted by pancreatic alpha cells

- targets liver

- increase glycogenolysis, gluconeogenesis, ketogenesis

- prevent hypoglycemia in response to fasting

glucagon mechanism of action

glucagon binds to glucagon receptor, Gs, adenylyl cyclase, cAMP, protein kinase A, ..., glycogen to glucose 1-phosphate (phosphorylase a) to glucose, glucose diffuses from high to low [] from GLUT2 transporters

increased plasma amino acids

stimulator for both insulin and glucagon (eg. eat steak)

proglucagon

contains 3 active hormones - glucagon, GLP-1, GLP-2

in alpha cells - main product is glucagon

in L cells of intestine and brain - main products are GLP-1 and GLP-2

diabetes mellitus - 2 types (type 2 ... exercise)

type 1 - insulin-dependent, juvenile

- insulin secretion reduced or absent

type 2 - non-insulin-dependent, mature onset

- defect in insulin secretion and target cell responsiveness to insulin reduced (bc chronic high glucose)

- treat with diet, exercise (causes translocation of GLUT4 to membrane!)

sulfonylureas - treating type 2 diabetes

closes potassium ATP channels, releasing insulin from vesicles, without need for glucose to be transported in through GLUT transporter

GLP-1 treatment for type 2 diabetes

- increase insulin synthesis and secretion

- increase beta cell growth

- effects on stomach, brain, and heart

delta cells in pancreas

somatostatin

Negative Feedback

Response that feeds back to stop stimulus. Stabilizing, homeostatic

Positive Feedback

Reinforces stimulus.

Which steroid hormone binds a membrane receptor?

Estrogen

3 Intracellular factors that are involved with stimulating hormone release

1. increase transcription of the hormone

2. Increase free cytosolic Ca (from entry of Ca as a signal molecule)

3. Increase Ca = increase of exocytosis of hormone

What scale are hormones released?

in pico-> nanometer levels (10^-12 -> 10^-9)

Which pancreas cells secret which hormone?

alpha - glucagon

beta - insulin

gamma - somatostatin

Which pathways are anabolic?

Glycogen synthesis, fat + protein synthesis

Which pathways are catabolic?

Gluconeogenesis, glycogenolysis, Fat oxidation

3 properties of insulin

- Binds a tyrosine kinase receptor

- decreases blood glucose

- increase glucose oxidation

- Brings GLUT4 receptors to membrane in muscle cells via exocytosis

- Activates a secondary messenger pathway via phosphorylation of IRS

- Activates hexokinase to phosphorylate glucose in the liver to maintain glucose gradient

Source of GIP

Source: Duo denum of intestine

Role of GIP

- Decreases gastrointestinal activity

- increases insulin release

Source of GLP-1

Source: ileum

Role of GLP-1

Increase insulin release

Decrease glucagon release

Increase beta cell growth

Inhibitors if insulin

Low glucose levels, somatostatin (locally), sympathetic nervous system

3 properties of glucagon

- secreted in response to low blood glucose

- peptide

- triggers adenyly cyclase signal cascade (Gs)

- stimulated by: plasma Amino Acids, low glucose, sympathetic nervous system

- inhibited by: high glucose, GLP-1, somatostatin

Source of growth hormone

Anterior Pituitary. peptide

Stimulants and inhibitors of growth hormone

Stimulants: GHRH, insulin, gherlin, fasting

Inhibitors: somatostatin, cortisol

IGF-1 inhibits GHRH

Role of GH

Stimulates IGF in liver + other catabolic actions

Required IGF + GH for growth

- Increase osteoblast differentiation, increase osteoprotegrin

Role of IGF

- Increase recruitment of chondrocytes

Source of thyroid hormones

Colloid of the thyroid follicle

What brings Iodine into the colloid

Na-I sympothers

What brings Tyrosine into the colloid?

Thyroglobin

Which thyroid hormone is most reactive? Which is more commonly found in blood?

T3 is more reactive

Find T4 more in blood, converted to T3 in cells

Source and role of TSH

Source: anterior pituitary, peptide

Role: Activate Gs pathway to activate thyroid hormone enzymes

What type of receptor do thyroid hormones bind?

As a (hetero or homo) dimer they bind nuclear thyroid receptors with retinoid acid

-Heterodimer is more common

Role if T3/T4

- Increase catabolic enzymes, metabolic rate, Oxygen consumption, heat production

- Increase thinking, reflexes, speech, beta-cell maturation for insulin production

Muscle: Increase development of fibres + repair, increase ATP usage + muscle usage

Heart: Increase beta-adrenergic receptors = Increase blood pressure and heart rate

Oogonium

Female germ cells, divides into primary oocytes during development and stops until puberty

Spermatogonium

Contains 2 sets of chromosomes until puberty. Meiosis after puberty produces 4 sperm

GnRH

- Pulsating release from hypothalamus neuroendocrine cells

- Stimulates rhythmic FSH and LH release

- Quiet pre-puberty

- Pulse/amplitude change during development

Role of testosterone and DHT in germ cell developement

- Stimulate sertoli cell proliferation and developement

Role of Lydia cells

produce steroid hormone, outside the basalateral membrane

Which hormone controls the follicular stage of ovary development? The luteal stage?

Follicular - estrogen

Luteal - Progesterone

Where are male germ cells make sure fetal development?

The testis

How many copies of chromosomes do each of the follow have?

1. Spermatogonia

2. Primary spermatocytes

3. Secondary spermatocytes

4. Spermatids

5. Spermatazoa

1. 2n copies

2. 4n copies

3. 2n copies

4. n copies

5. n copies

What is a key process that occurs in spermatozoa?

- active rearrangement of protein with in the cell

- elongation of nucleus

What are acrosomes?

Found in the top of nucleus hear of spermatozoa. Used for fusion with the egg

What does LH regulate in male spermatogenesis? What about FSH?

LH: Leydig cell differentiation and testosterone secretion

FSH: Sertoli cells

Role of Sertoli cells

secrete Androgen Binding protein (ABP), nutrients for development of spermatids

Secrete inhibit - inhibits FSH

How many days do spermatids spend traveling the epididymis? What happens during this time?

12-14 days

Get acted on by enzymes, increase mobility

Enzyme that converts testosterone to DHT

5-alpha-reductase

Role of DHT

- Increase spermatogenesis

- Stimulate secretion from prostate and seminal vesicles

- Increase sex drive

- Increase male hair growth

- Increase muscle growth

- Increase protein synthesis

- Increase aggression

At what phase do oogonia pause at until puberty?

Meiosis 1

How many primary oocytes are girls born with? How many left at puberty?

Born with 1-2 million, left with 300,000 at puberty

What is the role of theca cells and granulosa cells?

Theca - secret steroids

Granulosa - support oocyte development

What are the 3 phases of the ovarian cycle?

Follicular, Ovulation, Luteal

Which phase happens during day 1-14 of cycle?

Follicular

What must be secreted by theca cells to keep follicle alive during follicular phase?

Estrogen and progesterone

How do the 5-10 follicles that are recruited, end up becoming 1 follicle?

The dominant follicle secretes inhibiting hormone to block growth of the other follicles. Weaker follicles due from atresia

What main process happens during ovulation?

The follicle burst and secondary oocyte ovulates out of ovary.

fimbria - at end of fallopian tubes pick up egg

What is combos?

cloud of granulosa cells around the burst oocyte

Which hormone surges during ovulation? What does this cause?

LH surges.

Causes:

Follicular cells secrete collagenase - digests the connective tissue

Progesterone -> causes smooth muscle contraction - egg expelled out of ovary

What creates to corpus luteal?

Fusing of theca and granulosa cells from the dominant follicle

What happens if the ovulated egg is fertilized? If not fertilized?

Fertilized: corpus luteal provides nutrients during 1st trimester. Steroids maintain implantation of embryo.

Unfertilized: corpus luteal degraded to corpus albicans. Fibroblast breaks connective tissue

3 phases of Uterine cycle

Menses and proliferative, secretory

Main role of uterine menses phase

- decrease of steroid levels

- reduce blood supply

- shedding of lining

- during follicular phase of ovarian cycle

Role of uterine proliferative phase

- build the endothelium

- increase estrogen - division of endometrial cells and growth of blood vessels

Role of uterine secretory phase

- Endothelial cells grow + secret viscous fluid

- increase lipid and glycogen stores

- driven by progesterone

- coil of blood vessels -> important for fertile egg and blood for fetus

How does the body prevent further recruitment of follicles during menstruation

Granulosa cells secrete anti-mullerian hormone - prevents more follicle recruitment in response to FSH

What hormone mainly drives the 1st part of the menstrual cycle?

Estrogen

How is cholesterol converted to estradiol?

In theca cells: convert cholesterol -> androstenedione

Androstenedione enters granulosa cells:

converts to estrone by aromatase

Estrone -> Estradiol via 17 HDS 1

What happens if you have low aromatase levels?

Infertile, critical for creation of estradiol

What does regulation of menstrual cycle depend on?

LH - switches feedback midway through cycle.

When does the late luteal phase occur?

When there is no fertilization of the egg

Role of estrogen

- Increase follicular development

- Increase endometrium growth

- Negative feedback on GnRH, LH and FSH

- Increase fat on hip/legs

- Increase sex drive

- Increase hair growth

What is sperm coated with and why?

Coated with: albumen, enzymes, lipoproteins

Why: shields sperm from acidic environment in the vagina

What helps the sperm travel through uterine cavity along fallopian tubes?

Contractions and the movement of head and tail in sync

What guides the sperm to the fallopian tubes?

Chemotaxins

What happens after the sperm fuses with the egg?

Nucleus in sperm enters egg, oocyte finishes meiotic division -> divides into 2nd polar body and zygote

How long can sperm live in the fallopian tube?

up to 4 days

What is an ectopic pregnancy?

When the zygote implants on the side of fallopian tube and not in uterus

What is human chorionic gonadotropin?

Secreted from trophblasts, maintains corpus luteum and prevents the next menstruation cycle

- Makes its own hormones for fetus (Estrogen and progesterone)

What happens to trophoblasts at implantation?

Mature in contact with endometrium

Role of Syncitiotrophoblasts

lose cell membrane, invade endometrial lining from syncitia

Role of Cytotrophoblasts

Maintain plasma membranes form chorionic villi

Remain as individual cells right outside the inner cell mass

Decidua

Forms maternal endometrial cells in response to sustained high levels of progesterone

What happens during Week 2-10 of implantation?

Organogenesis

What is the role of the placenta?

Digestive, respiratory and renal functions

Excretes waste (CO2)

Allows O2, protein and chemicals in

What is the lacunae?

The 'lake' of maternal blood vessels, that allow blood and nutrients to diffuse in and out of uterus

What is human placenta lactose?

Specific hormone for pregnancy, high in mom, low in baby

Effects mother metabolism

What does prolactin do?

Creates epithelial milk producing cells

What is parturition?

Fancy name for birth

What happens when your 'water breaks'

Relaxin released by ovary, placenta loosens the ligament in pelvic bone and cervix contracts

Role of SRY gene

Creates SRY -> initiates transcription of SOX9 gene-> SOX9 which developed sertoli cells

(Male)