What are the philicities of these catagories of hormones?

Proteins:

Peptides:

prosteglandins:

Leukotrienes:

Catecholamines:

Steroids:

Thyroid hormone:

Proteins: Hydrophilic

Peptides: Hydrophilic

Prostaglandins: Lipophilic

Leukotrienes: Lipophilic

Catecholamines: Hydrophilic

Steroids: Lipophilic

Thyroid hormone: lipophilic

1. Protein/Peptide hormone binds surface receptor of target cell
2. Add P to internal specific proteins
3. P-Proteins generate response.

1. Protein/Peptide binds to receptor on cell surface
2. Add P to Tyrosine
3. P-tyrosine generates response

1. Protein/peptide hormine binds receptor
2. Activates G proteins by turning GTP -> GDP
3. G protein opens ion channels or modulates membrane enzymes
4. Generation of second messenger in cell
5. Second messenger activates protein kinase
6. Add P to specific proteins
7. P-proteins generate response. 

Receptor Regulation

Homologous

Heterologous

Homologous: modulation of receptor # by it's primary hormone

Heterologous: modulation of receptor # by a non-primary hormone

• Hormone A must be present for the full expression of hormone B's effect
• Hormone A or Hormone B alone have little to no effect
• (eg) Thyroid hormone & Epp

• 2 hormones have counter effects on a regulated variable
• (eg) glucagon & Insulin

• 1 hormone stimulates the secretion of another
• Adequate amounts are needed for growth and regulation of a cell

• Both hormones have a measurable effect
• Combined = big effect
• (eg) secretin & CCk

Protein & Peptide Hormones

Synthesis & Storage

• Secreted as a pre-pro-hormone
• Cleaved to a pro-hormone
• Cleaved to a hormone

Hormone packaged in vessicles & stored.

rapid response when needed

• Secreted by Ca dependent exocytosis
• Vesicles fuse, and release contents

Protein & Peptide Hormones

transport

• Hydrophylic
• travel in plasma
• polypeptides half life 4-40 minutes
• Proteins half life up to 3 hours

Protein & Peptide Hormones

post receptor events

receptor in cell membrane cause intracellular events

Ion Channel: hormone opens ion channel

Protein Kinase: Adds P to Tyrosine, P-Tyrosine causes response

Cytoplasmic JAK: binding adds P to cellular protein.  P-protein causes response

Protein & Peptide Hormones

G protein receptors

1. Activate G protein by turning GTP -> GDP
2. G protein opens ion channels or modulates membrane enzymes
3. Generation of second messenger in cell ↑ or ↓
4. Second messenger activates protein kinase which +P cell proteins to cause effect

1. cAMP
2. cGMP
3. IP3
4. DAG
5. Calcium-calmodulin

Steroids

Synthesis/Storage/Secretion

Synthesis: Made from cholesterol in adrenal cortex, testes, ovary, placenta

Storage: Made on demand

Secretion: immediately secreted, (slow action)

1. Estrogens
2. Androgens
3. Glucocorticoids (cortisol)
4. Mineralocorticoidsn(aldosterone)

Steroids

transport

• Lipophilic
• Mostly bound to plasma proteins
• Half life of hours because bound
• Metabolized in liver
• Lipophilic metabolites secreted into bile for excretion in feces

Steroids

Post receptor events

• pass cell membrane into cell
• binds to receptors at nucleus or cytoplasm
• DNA expression, protein synthesis

Slow biological response

• Tyrosine -> EPP, NE, T3, T4
• Exibit peptide or steroid action on cell
• catecholamines: Action like peptides
• Thyroid hormones: Action like steroids

• Made by all tissue
• Made by cyclooxygenase from arachidonic acid. 
• Irreversibly inhibited by NSAID. 
• Type of prosteglandin dependent on complement enzymes of the cell.
• Paracrine/autocrine
• Half life seconds to minutes. 

• Made in all cells
• Made by 5-lipoxygenase from arachidonic
• Not inhibited by ASA
• paracrine/autocrine
• half life seconds to minutes

Gametogenesis

first miotic division

• During ovulation
• Generates a secondary oocyte, and a first polar body.
• both cells have 23 chromasomes, 2 chromatids each.

Gametogenesis

Secondary miotic division

• Happens after fertilization by a sperm
• Produces mature ovum and second polar body
• Each cell has 23 chromosomes, 1 chromatid each.

Granulosa cells secrete:

primordial

Primary

Secondary

Antral

primordial: MIF

Primary: Mucopolysachurides for Zona Pellucida

Secondary: Autocrine agents for Thecal cells

Antral: fluid for antrum

Selection of the dominant antral follicle

When:

Which hormone:

• Day 7 of menstral cycle
• 1 antral follicle selected, driven by inhibin
• Other antral follicles degenerate
  

Ovulation of Graafian follicle

Which hormone:

What is released:

• LH
• Graafian follicle ruptures due to BIG antrum
• releases oocyte+zona pellucida+thin layers of granulosa
• baloons out of ovary surface

Menstruation

(Summery)

1

7

15

25

1: Bleed

7: Selection of dominant antral follicle

15:Ovulatory phase (Graafian follicle ovulation)

25:Degeneration of corpus luteum

Menstration

(Summery)

1-6

8-14

16-24

26-28

1-6: Secondary follicles -> antral follicles

8-14: Dominant follicle secretes estrogen

16-24: After ovulation, Graffian becomes corpus luteum.  Secretes Progensterone + estrogen

26-28: ↓ Progesterone ↓ Estrogen sloughing

Follicular phase

1-5

7

7-14

1-5: menstruation, secondary -> antral follicles

7: Antral that secretes most Estrogen chosen

7-14: Dominant grows.  secretes Estrogen into blood

14: ↑ plasma estrogen (day 12) -> LH (day 14)

proliferation of uterine endometrium

Ovulatory phase

Day 15

• Dominant -> Graffian
• Oocyte resumes meiosis, completes first devision
• ovulation after 16 hours of LH surge
  

Luteal phase

16-24

25

26-28

• Graafian -> corpus luteum
• Corpus luteum produces PROGESTERONE & estrogen
• Progesterone blocks proliferation of endometrium and induces secretion
• 14 days after ovulation, corpus luteum dies
• ↓ estrogen & progesterone, endometrium sheds.
  

Down regulated GnRH,

Less receptors on gonadotropin secreting cells

Lowers FSH & LH

GnRH

Slow pulse

Fast pulse

Slow = FSH

Fast = LH

LH

in the follicle stage

• LH binds to receptors on thecal cell
• Androgen synthesized (androstenedione & Testosterone)
• Androgens diffuse into granula cells
• Aromatase turns them into E1 and E2

FSH

Follicle stage

• FSH binds to receptors on granulosa cells
• stimulation of activity of aromatase
• more intra follicular estrogen produced.

• Some enters blood
• Some acts on granulosa to ↑ FSH receptors, estrogen receptors, LH receptors.

E1

E2

E3

E1 = Estrone

E2 = Estradiol

E3 = estri'ol

• Secondary follicle -> Antral follicle
• ↑ Growth of follicle
• ↑ proliferation of granulosa cells
• ↑ LH granulosa receptors (more progesterone for luteal phase)
• ↑ FSH Granulosa receptors (late follicular)
• ↑ Estrogen receptors in granulosa cells
  

Estrogen effect on reproductive tract

• Cause uterine cervix secrete thin watery mucus
• contract smooth muscle of uterus & fallopian tube
• proliferation of uterine endometrium & smooth muscle
• ↑ progesterone receptors in uterus
  

• Puberty
• Bone deposition
• more plasma proteins
• ↑ HDL, ↓ LDL
• close epiphyseal plates
  

most often

• ↓ production of GnRH, LH & FSH

At this time receptors to GnRH few

Before ovulatory phase

• ↑ GnRH pulse (LH)
• ↑ GnRH receptors
  

• E2 and E1 converted into E3 (metabolizable) or 2-methoxyestrone (not metabolizable)
• metabolites + glucuronides or sulfates.  water soluble so can be excreted urine/feces
• (smokeing metabolizes estrogen)

Hormone order for:

Secondary -> Antral -> Dominant

1. FSH ↑ production of Estrogen & Inhibin
2. secondary --Estrogen--> Antral
3. High Inhibin picks dominant, and ↓ FSH
   

• Due to Estrogen + feedback
• 48 hours after Estrogen spike
• Most decisive event in menstral cycle!
• Only in females.
• Results in Graafian follicle

1. Graafian expands, popping out ovum
2. remaining granulosa cells converted into corpus luteum by LH

• First generation oral contreseptive
• Inhibit ovulation, by negative feedback
• Estrogen high enough so not completely metabolized by liver
• Estrogen low enough so not threshhold level
• BAD: too much estrogen = cancers due to over proliferation

• Prevent implantation
• RU 486 (Progesterone antagonist)
• If uterus smooth muscle keeps contracting, ovum can't implant.

Luteolysis

1. Corpus luteum less sensitive to LH
2. ↓ Progesterone made
3. Ischemia
   

Menstral fluid:

(Why lesbian vampires meet monthly)

• 40 ml bood
• 35 ml serous fluid
• Fibrinolysis prevents clotting
• WBC

• Secreted from syncytiotrophoblast to fetus & mother
• β subunit similar to LH
• Binds to LH receptors on granulosa & follicle to ↑ secretion of progesterone.
• Measured in maternal plasma by 6-8 days!
• max lvls at 60-90  days, then decline & plateau.

• Elevated entire duration
• Always higher than estrogen
• Made from cholesterol by placenta, independently of "external regulatory factors" (mother's FSH/LH)
• Placental secretion proportional to placental weight
• bad indicator for fetal health.

Progesterin

physiological effect during pregnancy

• Breasts for lactation
• supress immune response
• ↑ ventilation
• ↓ prostaglandin in uterine smooth muscle
• ↑ apetite
• ↓ AA breakdown by liver (so fetus can use)

Estrogen

in pregnancy

• First 8 weeks secreted by corpus luteum under action of hCG, later by placenta.

• Placenta lacks 17-alpha-hydroxylase.
• Placenta makes pregnenolone and diffuses into fetus
• fetus turns pregnenolone into estriol (E3)
• E3 in urine is a good indicator for fetal health

• Prolactin secreting hormone
• from pituitary
• ↓ by dopamine (usually continuously supressed)
• ↑ by prolactin releasing hormone & estrogen
• breast structural development
• enzymes for milk development
• inhibit GnRH

Human placental lactogen

• Breast structural development
• Milk secretion
• Anti insulin effects

Menopause

Early

• Small cohort
• ↓ Estrogen, ↓ Inhibin (↓ negative feedback)
• ↑ FSH > ↑ LH
  
• Shorter follicular phase (because of ↑ FSH)
  
• Shorter cycle
  

Menopause

Medium

• Very small cohort
• ↓ Estrogen 
• Delayed (+) feedback
•  Longer follicular phase
•  Longer cycle

Menopause

Late

• ↓↓ Estrogen 
• No posative feedback 
• Anovulatory (no ovulation)
• Enough Estrogen to cause menstruation
• Menstrual period becomes less regular
  

(Eventually 0 Estrogen = no menstruation)

Peripheral conversion of Androgens -> Estrogen

(Menopause)

• LH binds to stromal (non follicular) cells in ovary
• Cells become hypertrophic (big) and synthesize androgen
• No follicles = no granulosa = no conversion of androgens into estrogen
• Androgens travel in blood and are converted into estrogen by peripheral tissue.

• ↓ Plasma Estradiol (E2)
• Estrone (E1) > Estradiol (E2)
• Increase in FSH & LH
• Plasma Androgens remain normal
  

• Atrophy of Estrogen dependent tissue
• Alkaline PH of vaginal secretion (risk of vaginitis)
• Hot flashes
• ↑ Cholesterol and LDL, ↓ HDL
• ↑ change of Stroke or heart attack
• Osteoperosis