Exogenous Hormone Use Flashcards
HPO Axis General Principles
- Hypothalmaus produces GnRH
- GnRH acts on anterior pituitary and stimulates production of LH and FSH
- FSH causes maturation of follicles, acts on granulosa cells
- Granulosa cells convert androgens to oestradiol
- Inhibin is produced by granulosa inhibits secretion of FSH
- Follicles become dependent on LH due to inhibin production
- LH surge is stimulated by high levels of oestradiol when it reaches positive feedback threshold
- LH stimulates ovulation of dominant follicle
- Ovulation of dominant follicle results in corpus luteum
- CL produces progesterone which has -ve feedback effect on hypothalamus and suppresses GnRH
- CL also produces oxytocin which binds to OXTR in endometrium
- Endometrium secretes PGF2a which lyses CL
How can we use exogenous hormones to manipulate HPO axis
Directly control follicular and luteal function
* FSH to stimulate follicular growth
* hCG to stimulate ovulation (LH-like activity)
* PGF2a to stimulate luteolysis
Indirectly control follicular and luteal function
* GnRH - LH effect is likely to dominate
Control hypothalamus
* Suppress HPO axis with progesterone
* longer duration needed
What does GnRH/LH need to trigger ovulation?
Dominant follicle
What does FSH require to recruit multiple dominant follicles?
Growing antral follicles
What does PGF2a require to function?
An active CL
Classes of reproductive drugs
- GnRH agonists
- Gonadotrophins
- Sex steroids
- Prostaglandins
- Prolactin inhibitors
- Other
GnRH agonist Examples
○ Buserelin
○ Gonadorelin
○ Deslorelin
○ Peforelin
Short Term GnRH agonist Action
○ Hasten impending cyclicity/oestrus
* E.g. lactational anoestrus in cows
* Post weaning in gilts/sows
○ Hasten ovulation by inducing LH surge (and FSH)
* Normal oestrous cycle
* Part of synchronisation protocol (fixed-timed AI)
○ “Force” ovulation/luteinisation of cystic structures
○ Test hypothalamic-gonadal axis
* E.g. GnRH stimulation test and measure sex steroid response - testis
Long Term GnRH agonist Action
○ Initial stimulation and then down-regulation GnRH receptor and thus suppresses HPG axis
○ Control behaviour & fertility in male dogs (for up to 6 months)
○ Control/suppress oestrus behaviour
○ Also used in humans in IVF protocols
Gonadotrophin Examples
hCG (LH like activity)
eCG (FSH like activity)
FSH
Gonadotrophin Action (FSH)
- Stimulates antral follicle growth
- If we can provide support during selection process, will end up with multiple dominant follicles
- Few FSH products available - can use eCG
Clinical uses:
○ As part of oestrus / ovulation induction regimes
○ Ovulation of more follicle than normal
Need to administer before dominance has occurred
Give multiple doses
○ Must administer early in follicular wave for superovulation
○ Often, requires repeated doses
○ Ineffective in the mare (causes follicular growth but not superovulation)
Gonadotrophin Action (LH)
- Stimulates final maturation of follicles, luteinisation and provides luteal support
- No LH specific product
○ Use HCG: binds to LH receptor and has LH-like activity
Clinical uses:
○ Induce ovulation when animals are in oestrus
○ Hasten ovulation in AI regimes
○ To force ovulation when there has been repeated failure of conception in cattle
○ Treatment of cystic ovaries in cows and heifers
○ Treatment of prolonged pro-oestrus in the bitch
○ Deficiency of libido in male dogs
Sex steroid examples
○ Androgens (e.g.nandrolone)
○ Progestogens (e.g. progesterone, proligesterone)
○ Oestrogens
○ Progesterone antagonists (e.g. aglespristone)
Progesterone Action
Negative feedback on HPO axis - reduces GnRH production
Effects on target tissues:
○ Mammary enlargement
○ Endometrial proliferation/histotroph production
○ Sedative-like effects on behaviour
Clinical use of progestogens:
Prevent oestrus in dogs, mares
Treat and prevent of pseudopregnancy in dogs
Treat some male conditions like unwanted behaviour / prostatic disease
Inducing/synchronising oestrus by administration and withdrawal (PRIDs)
Exogenous progestogen methods
- Vaginal
○ Vaginal sponges (Ewes)
Oestrus induction / synchronisation upon withdrawal (often in combination with eCG)
○ Vaginal devices (PRID/CIDR in mares, cows)
Oestrus induction / synchronisation (in combination with GnRH/PGF2A) - Depot
○ Depot progestogen injections
Prevention oestrus in bitches - Oral
○ Oral progestogen tablets
Prevention of oestrus in dogs / suppression of oestrus
○ Oral liquids
Oestrus suppression / induction / synchronisation in mares/sows
