Hormonal Basis of Reproduction Flashcards
What is a hormone?
CHEMICAL MESSENGERS released from certain cells into circulation to control activity of specialized (TARGET) cells, tissues, or organs (usually have minimal overlap of biological activities, thus deficiencies can cause major abnormalities)
What are targets?
can be a few or many cells, tissues, or organs (must have specific receptors for each hormone)
What is transport?
can be:
- FREE (in solution; mostly for water-soluble hormones)
- or bound (to binding proteins; mostly for lipid-soluble hormones, ex: testosterone BP)
What are receptors?
EXTRACELLULAR or INTRACELLULAR to target cells
What is the first messenger?
hormone that binds to extracellular RECEPTORS (promotes release of SECOND MESSENGER in cell)
What is the second messenger?
intermediary mc that appears due to hormone-receptor interaction (ex: cAMP, cGMP, Ca^2+)
-> may act as enzyme activator, inhibitor, or cofactor & results in changes in rates of metabolic rxns
What is amplification?
magnifies the effect of a hormone on a target cell (few hormone mcs bind to extracellular receptors, but 1000s of 2nd messengers may appear)
What is half-life?
time required for one-half of hormone to disappear from blood/body (determines how fast a hormone is metabolized)
What is it called when neurons release chemical messengers in the blood?
(neuro)HORMONES
What is it called when neurons release chemical messengers across synapses?
Neurotransmitters
How do hormones work?
- SYSTEMIC (neuroendocrine or endocrine)
- control specific physiological processes ANYWHERE IN BODY
- send hormonal messages to essentially all cells by secreting into BLOOD but ONLY TARGET CELLS/TISSUES RESPOND
- comparable to radio signals or MOBILE PHONE SIGNALS
- endocrine messages travel slower, but response is LONGER-LASTING & WIDESPREAD on multiple tissues/cells at the same time
How do neurotransmitters work?
- POINT-TO-POINT
- controls specific processes @ SPECIFIC CELLS/TISSUES CONNECTED BY NERVES
- comparable to signals sent through a landline phone
What are 3 ways of classifying reproductive hormones?
- biochemical structure
- source
- mode of action
What are the classes of biochemical structure of reproductive hormones?
- peptides
- glycoproteins
- steroids
- prostaglandins
What are the classes of sources of reproductive hormones?
- hypothalamus
- pituitary
- gonads
- uterus
- placenta
What are the classes of mode of action of reproductive hormones?
- release of other hormones (releasing hormone)
- stimulation of gonads (gonadotropins)
- sexual promotion (steroids)
- luteolysis (destruction of the corpus luteum)
Why is the biochemical structure of reproductive hormones important?
- peptide hormones tend to have a shorter chain of AA & therefore a shorter half life. this makes them difficult to measure & you will need to collect the blood sample from near where they are released
- glycoprotein hormones have a much longer half life due to their structure
What is an example of a peptide hormone?
GnRH
What are some examples of glycoprotein hormones?
LH & FSH
What are some examples of some steroid hormones?
Estradiol (E”2”) & progesterone (P”4”)
Why are modified fatty-acid derived prostaglandins not considered part of the classic/typical hormones?
- b/c they mainly have an autocrine/paracrine function
- yet they have important implications in repro management
What are peptide hormones?
MOST REPRO & OTHER HORMONES OF THE BODY (ex: all hypothalamic, pituitary, some gonadal)
What is the structure of peptide hormones?
chains of a.a. (3 to >200)
What is the solubility of peptide hormones?
HYDROPHILIC (water-soluble)
What is the synthesis of peptide hormones?
rER, packaged in the Golgi
What is the storage of peptide hormones?
secretary granules
What is the secretion of peptide hormones?
exocytosis
What is the half-life of peptide hormones?
short (compared to steroids)
What is the transport of peptide hormones?
mostly as free hormone
Where are the receptors of peptide hormones?
surface of target cell
What is the action of peptide hormones?
mostly 2nd messenger system or channel changes, may activate genes
What are steroids?
estrogen, progesterone, androgens
What is the structure of steroids?
cholesterol derivatives
What is the solubility of steroids?
LIPOPHILIC (lipid soluble)
What is the synthesis of steroids?
stepwise modification of cholesterol in various intracellular components
What is the storage of steroids?
hormone is not stored, only the precursor is
What is the secretion of steroids?
diffusion
What is the transport of steroids?
mostly bound to plasma proteins
What is the half-life of steroids?
long
Where are the receptors of steroids?
inside of target cell (cytoplasmic/nuclear)
What is the action of steroids?
mostly direct effect on genes to produce new proteins
What are 4 different reproductive hormone secretory patterns?
- pulsatile (episodic or tonic)
- surge (sustained or phasic)
- cyclic
- circadian & circannual
What is pulsatile (episodic or tonic) hormone secretion?
- pattern of release for most hormones (ex: LH, testosterone)
- quickly reach a peak, then decline to basal lvls (half-life dependent)
- frequency & amplitude of pules & basal and mean concentration calculated
- single blood samples are usually inadequate for diagnosis
What is surge (sustained or phasic) hormone secretion?
- prime ex is preovulatory GnRH/LH surge
- hypothalamus tonic center releases 1-3/hr sm GnRH pulses
- only in females, it also has a surge center for v large amplitude pulses back-to-back for several hours to stimulate LH surge & cause ovulation
What is cyclic hormone secretion?
- in females during reproductive age, reproductive hormones follow a general cyclic pattern, influenced by HPG axis & ovarian activity
What is circadian & circannual hormone secretion?
- some hormones vary ACROSS THE 24 hr CYCLE (CIRCADIAN); ex: approaching puberty, LH increases in urine of boys @ night
- some hormones vary by season (CIRCANNUAL); ex: reproductive hormones in seasonal breeders
- MELATONIN main signal for both patterns by reflecting length of night
How is hormone secretion controlled?
- hormones use a control system that works like a thermostat to maintain homeostasis
- can be adjusted upward or downward in response to patho/physiological status
- controlled by both negative & positive feedback
What is negative feedback?
- acts to minimize deviation from the setpoint
- leads to stability
- main control mech for most hormones
- 2 hormones keep each other w/in normal range
- also important in dx of hormone disorders
what is positive feedback?
- acts to increase deviation from setpoint
- leads to INSTABILITY
- occurs in ONLY A FEW SITUATIONS
- INCREASED TARGET HORMONE POTENTIATES INITIAL HORMONE RELEASE, in turn causing more target hormone release, which again encourages even more initial hormone release
- cycle continues until something gives in (ex: parturition, ovulation, milk letdown)
What are two examples of positive feedback loops?
- baby drops lower in uterus to initiate labour -> cervical stretch -> stimulates oxytocin release -> causes uterine contractions -> pushes baby against cervix -> causing more cervical stretch and the cycle repeats until delivery of the baby stops the cycle
- Stimulus: baby suckles @ nipple -> suckling sends impulses to hypothalamus -> hypothalamus signals to posterior pituitary to release oxytocin -> oxytocin released into bloodstream stimulates milk ejection from mammary gland -> milk is released & the baby continues to feed and the cycle continues
What are extracellular (cell membrane) receptors)?
APPLIES TO ALL PEPTIDE HORMONES.
they are G - PROTEIN COUPLED RECEPTORS (GPCRs)
What are G-Protein coupled receptors?
- receptors w/ 7-pass (goes back & forth 7x) transmembrane domains
- modulate enzymes or ion channels indirectly, thru G proteins & 2nd messengers
- involved as a link btwn 1st & 2nd messenger
- G proteins function as molecular switches (when they bind GTP they are ‘on’; when they bind GDP they are ‘off’)
- ex: LH, FSH, GnRH, hCG
- can be activated by various ligands (hormones, NTs, growth factors, light, drugs)
- > 30% of all drugs target G proteins
- > 800 known types of G proteins
- 9 Noble prizes over time given to GPCR discoveries
How does the hypothalamus control the anterior pituitary?
- neurosecretory cells secrete releasing or inhibitory factors
- they are released near capillaries of the hypophyseal portal system at the median eminence
- transported efficiently to the anterior pituitary gland to regulate the secretion of pars distalis hormones
- parvicellular neurosecretory cells -> hormone transport in axons -> hypophyseotropic hormones released -> hormone transport in blood -> stimulation or inhibition of anterior pituitary hormone release -> hormone transport in blood -> action on endocrine glands
What are portal vessels?
blood vessels that link 2 capillary networks
What does the hypophyseal portal system do?
ensure that regulatory hormones reach cells in the anterior pituitary before entering the general circulation
What is the median eminence?
swelling near attachment of infundibulum where hypothalamic neurons release regulatory hormones into interstitial fluids. these hormones enter the bloodstream through fenestrated capillaries
How do gonadatropes work?
- they are acted on by a hypothalamic regulator
- tropic hormone is secreted in pituitary gonadotrope
- goes to its receptor
- target endocrine gland action
- negative feedback hormones
What is the hypothalamic regulator?
Gonadotropic-releasing hormone (GnRH)
- 10 a.a. peptide
- stimulatory
What tropic hormones are secreted due to stimulation from GnRH?
follicle-stimulating hormone (FSH) & Luteinizing hormone (LH)
- 213 & 210 a.a. (33 & 28 kDa) glycoprotein
- have alpha & beta subunits
- half-life: FSH - 3 hrs; LH 0.5 hr
- pulsatile
What are the receptors for the secreted tropic hormones?
FSH & LH receptors (G”2” protein coupled)
What are the target endocrine glands for FSH & LH?
- ovary (granulosa & theca cells)
- testis (sertoli & leydig cells)
What are the negative feedback hormones?
- Estrogen: acting on the GnRH neurons; @ low lvls has negative feedback, but when you pass a certain threshold (when follicle is producing a lot of estrogen) it becomes a positive feedback)
- progesterone
- testosterone
- inhibin: selective negative feedback on FSH
What pulses in response to GnRH pulses?
LH pulses in response. It’s half life is shorter, so it comes down sharper
What is the structure of a glycoprotein?
LH & FSH as well as TSH & hCG are all glycoproteins
- have 2 subunits
- alpha is the common subunit
- beta is the hormone specific subunit
What are intracellular receptors?
Applies to all steroid hormones.
CYTOPLASMIC OR NUCLEAR RECEPTORS:
- b/c of lipid solubility, steroids can diffuse through the cell membrane to bind to receptors
- nuclear receptors for sex steroids
- but cytoplasmic for most other steroids
- can ALTER RATE OF DNA TRANSCRIPTION in nucleus
- alter synthesis of enzymes or structural prots
- directly affects activity & structure of target cell
Process: Diffusion through mb lipids -> binding of hormone to cytoplasmic or nuclear receptors -> binding of hormone-receptor complex to DNA -> gene activation -> transcription o& mRNA production -> translation & protein synthesis -> alteration of cellular structure or activity -> target cell response
Gonadotrope process
CNS inputs: puberty, opioids, stress, prolactin acting on GnRH neurons -> Pulsatile release of GNRH @ median eminence -> GnRH on GnRH receptor on pituitary gonadotrope -> Ca^2+, protein kinase C (PKC), other pathways -> fast GnRH pulses leading to LH synthesis & secretion OR slow GnRH pulses leading to FSH synthesis & secretion -> Released LH & FSH acting on LH & FSH receptors on gonadal cell types -> protein kinase A (PKA) -> steroidogenesis or gametogenesis -> sex steroids or inhibin
- inhibin -> inhibin selective negative feedback on FSH
- sex steroids -> positive & negative feedback on pituitary gonadotropes & GnRH neurons (ex: estrogen has feedback on GnRH: @ low lvls negative, @ high lvls positive)
Genomic vs nongenomic action of steroids?
- new evidence points to a more complex picture for steroids
- IN ADDN TO THEIR TYPICAL GENOMIC ACTION mode (slow response) through intracellular receptors, steroids can initiate fast RESPONSES THROUGH GPCRs (nongenomic)
Pathways of action of steroids and examples of fast & slow responses?
Steroid hormone bound to carrier travels through the blood in a capillary ->
-> Fast response -> Binds to G protein coupled receptor -> adenylate cyclase converts ATP to cAMP -> which activates protein kinases -> new protein synthesis -> new protein products for reproduction
Fast response ex:
- estradiol -> ion channel alteration -> increased myometrial contractions
- progesterone -> ion channel inhibition -> decreased myometrial contractions
-> slow response -> migrates into cytoplasm through plasma mb & binds to receptor in nucleus of cell -> producing mRNA -> new protein products for reproduction
Slow response ex:
- estradiol -> mucous secretion by female tract
- progesterone -> uterine gland secretion
What alters the physiological activity of hormones?
- pattern & duration of secretion (pulsatile vs sustained)
- half-life (sec, min, hr, days)
- receptor density (from 2,000 to >100,000; higher density = higher potential response: cell type, up-regulation (promotion of receptor synthesis by same or other hormones), or down-regulation (inhibition of receptor synthesis))
- receptor-hormone affinity (greater affinity = greater response: native hormone, agonists (bind the same receptors & cause same or higher response), and antagonists (bind the same receptors but cause no or a weak response)
What are the interactions of reproductive hormones?
- cells have more than 1 type of hormone receptor, so can response to multiple hormones simultaneously
- receiving instructions from 2 HORMONES @ SAME TIME has multiple possible outcomes (ANTAGONISTIC (opposing) EFFECTS, ADDITIVE EFFECTS, & PERMISSIVE EFFECTS)
What are antagonistic (opposing) effects?
- net result depends on balance btwn hormones
- in general, observed effects are weaker than those produced by either hormone unopposed
- ex: estrogen vs progesterone actions (generally)
What are additive effects?
- net result from 2 hormones is greater than each acting alone
- in some cases, result is greater than the sum of individual effects called a synergistic effect
- ex: testosterone & FSH promote sperm production
What are permissive effects?
- 1 hormone is needed for 2nd hormone to produce its effect
- ex: oxytocin works best in presence of estrogen
How are hormone lvls measured?
Measurement methods include:
- immunologic methods (RADIO-IMMUNOASSAYS (RIA): needs special labs; ENZYME-LINKED IMMUNOSORBANT ASSAY (ELISA); immunohistochemistry (IHC): on histo-slides)
- bioassays (in vitro: using cells in culture; in vivo: using amphibians for MSH)
- radioisotope techniques
- molecular biology techniques
How does hormonal metabolism & clearance work?
- blood concentrations reflect net of SECRETION VS METABOLISM rates
- may or may not be degraded before elimination in bile or urine
- some metabolites remain biologically active in feces/urine
- most protein hormones are degraded by the liver & kidneys
- others by serum proteases or target cells
- IN LIVER, STEROIDS METABOLIZED (become water-soluble & inactivated by conjugating glucuronide or sulfate residues) to be excreted in urine or feces
Diagram ex: - progesterone in blood -> goes into liver -> released back into blood as sodium pregnanediol glucosiduronidate -> excreted in urine
- testosterone in blood -> goes into liver -> released back into blood as sodium androsterone glucuronide & sodium etiocholanolone sulfate -> excreted in urine
What are normal hormone lvls?
- normal hormone lvls are extremely low, ranging from nanograms (10^-9) to picograms (10^-12) per mL of blood
How does ELISA work?
Hormone binds to hormone antibody creating the hormone-hormone-antibody complex -> enzyme binds (linked) to this complex -> the reaction of this enzyme w/ its substrate generates colour
