Principles of exogenous hormone use Flashcards
What are the three ways hormones can control ovarian and uterine function?
Direct control – Acting on follicles (FSH, LH) or corpus luteum (PGF2α, progesterone)
Indirect control – Stimulating GnRH to influence gonadotropin release
Hypothalamic control – Using progesterone to suppress GnRH & reproductive cycles
Give examples of how the stage of cycle impacts our choice of drug
Different ovarian structures will be present and/or dominate at different stages:
- Active CL needed for PGF2A to act
- Dominant (large) follicle needed for GnRH (LH) to trigger ovulation
- Growing antral follicles needed for FSH to recruit multiple co-DF
Give examples of GnRH agonists
Buserelin
Gonadorelin
Deslorelin
Peforelin
Give examples of gonadotrophins used as exogenous hormones
HCG (LH like activity)
ECG (FSH like activity)
FSH
Give examples of sex steroids used a exogenous hormones
Androgens (e.g.nandrolone)
Progestogens (e.g progesterone, proligesterone)
Oestrogens
Progesterone antagonists (e.g. aglespristone)
Give examples of prostaglandins used as exogenous hormones
Dinoprost (synthetic natural)
Cloprostenol
Luprostiol
Give examples of prolactin inhibitors used as exogenous hormones
Cabergoline
Describe the short term action of using GnRH as an exogenous hormone
Hastens impending cyclicity/oestrus (ie lactational anoestrus in cows, post weaning in gilts/sows)
Triggers ovulation by inducing LH surge
Part of synchronisation protocol (fixed-timed AI)
“Force” ovulation/luteinisation of cystic structures
Test activity of hypothalamic-gonadal axis i.e. GnRH stimulation test
Describe the long-term action of GnRH as an exogenous hormone (deslorelin implant)
Initial stimulation and then down-regulation of GnRH receptor - thus suppresses HPG axis
Control behaviour & fertility in male dogs (for up to 6 months)
Control/suppress oestrous behaviour
Used in human IVF
Describe the clinical use of FSH
As part of oestrous induction regimes; often given in conjunction with progestogens
Ovulation of more follicle than normal (superovulation):
- Must administer early in follicular wave for superovulation
- Requires repeated doses and responses are varied
- Ineffective in the mare
Describe the clinical uses of HCG as an exogenous hormone
LH like activity:
- Induce ovulation when animals are in oestrus
- Treatment of prolonged pro-oestrus in the bitch
- Deficiency of libido in male dogs
Describe the effect of using progestogens as an exogenous hormone
Progesterone has a negative feedback effect upon the hypothalamus/pituitary
Progesterone also has effects on target tissues eg:
- Mammary enlargement
- endometrial proliferation/histotroph production
- Sedative-like effects on behaviour
Describe the clinical use of sex steroids (progestogens) as an exogenous steroid
Suppress the hypothalamic-gonadal axis to:
- Prevent oestrus in dogs, mares
- Treat and prevent of pseudopregnancy in dogs
- Treat some male conditions like unwanted behaviour / prostatic disease
Used as method of inducing/synchronising oestrus by administration and withdrawal of the product
Give examples of different formulations of exogenous progestogens
Vaginal:
- vaginal sponges (ewes)
- vaginal devices (mares, cows)
Depot:
- depot progestogen injections (to prevent oestrus in bitches)
Oral:
- progestogen tablets (dogs)
- liquids (sows, mares)
Describe the use of progesterone receptor antagonists as exogenous hormones
PR antagonist displaces progesterone from its receptor but produces no signal => Endogenous progesterone is ineffective although plasma concentrations are normal
Clinical uses:
- termination of pregnancy in the dog (only licensed use)
- Will terminate pregnancy in any species
- Can induce parturition
- Can ‘treat’ conditions stimulated by progesterone (e.g. pyometra in the bitch / mammary hyperplasia in the queen)
Describe the use of sex steroids (oestrogens) as exogenous hormones
Most oestrogens were used for their effects on target tissues:
- Tissue development in the vagina, urethra and mammary gland
- Growth and function of the uterine tube and uterus
In clinical practice, oestrogens are not used for “reproductive” considerations:
- used for control of urinary incontinence
Describe the effect of endogenous prostaglandin F2a
Lysis of the mature CL, causing progesterone to decline. Although early CLs are usually not responsive1
Smooth muscle contraction i.e. ecbolic effect on uterus
Describe the clinical uses of exogenous prostaglandin F2a
Termination of luteal phase to synchronise oestrus
Induction of abortion
Induction of parturition
Ecbolic effect:
- Treatment of chronic metritis
- Treatment of pyometra (if CL is present)
What is the effect of endogenous LH?
Stimulates final maturation of follicles, luteinisation and provides luteal support
What is the effect of endogenous FSH?
Stimulates antral follicular growth
What is the effect of endogenous prolactin?
endogenous prolactin supports CL function (i.e. luteotrophic)
What is the effect of prolactin inhibitors and its clinical uses?
Prolactin inhibitors remove luteal support, thus CL lysis => termination of luteal phase and progesterone declines. Like PGF2A but fewer adverse effects and no ecbolic effect
Clinical uses:
- To end the luteal phase, to terminate pregnancy and treat pyometra
- To reduce milk production and behaviour of pseudopregnancy
- To reduce milk after weaning
- To induce oestrus
Describe the function of endogenous melatonin in cyclicity
Endogenous production in response to decreasing daylight length
Up-regulates HPO axis in short-day breeders
Down-regulates HPO axis in long-day breeders
What are the clinical uses of exogenous melatonin
Give melatonin to ewes = brings on cyclicity / oestrus
Give melatonin to mare / cat / ferret = suppresses cyclicity / oestrus
Give light to mare / cat / ferret = brings on oestrus
No melatonin antagonists are available
Ewe - Melatonin implant administered at base of ear in May-June to hasten onset of cyclicity (+ introduction of the ram)
