Reproductive Pharmacology

Reasons for reproductive pharmacological interventions

Manipulate follicular waves

Induce ovulation
Control luteal phase
Oestrus synchronisation/stimulating ovarian activity/advancing onset of oestrus in seasonal species (influencing litter size)
Control/induce parturition
Misalliance

Suppressing reproduction

Explain the HPG (Hypothalamus Pituitary Gonads) axis

GnRH release from hypothalamus
FSH & LH release from pituitary
Release of testosterone, progesterone & oestrogen

GnRH (Gonadotropin Releasing Hormone) key features

•Peptide hormone
•Proteolytic degradation
•Short half life 70- 80 mins

Why should GnRH not be given continually?

Mimics the GnRH pulse generator

If given continually then GnRH receptors get downregulated so pituitary can't release LH & FSH

chemical castration

e.g. implants that continuously release GnRH

What do GnRH agonists do? What can it be used for?

Stimulate LH & FSH surge (due to acute release of gonadotropins from pituitary)

Induce ovulation

Improve synchronisation of oestrus/ovulation

Improve conception rates

What does GnRF stand for?

What does the vaccine do?

What can it be used for?

Gonadotrophin Releasing Factor

Induces antibodies against GnRH —> immunity (anti GnRF antibodies) develop around 1 weeks post 2nd vaccination

Chemical castration of pigs

can prevent boar taint if pigs are on farm for too long

What does LH do in females and males?

Females

- produces precursors for oestrogen production

- stimulates maturation and ovulation of follicles

- maintains function of CL

Males

increased testosterone by Leydig cells

What does FSH do in males and females?

Females

- growth & recruitment of immature follicles

- stimulates oestrogen synthesis

Males

promotes spermatogenesis

What produces gonadotrophins? What type of macromolecule are they?

Anterior pituitary (under hypothalmic control)

Glycoproteins —> more resistant to breakdown than peptides/proteins

metabolised by proteases

What can FSH induce in cows?

Superovulation

Why would PMSG (Pregnant Mare Serum Gonadotropin) be used instead of FSH? What is it used for?

Longer half life, cheaper

Oestrus induction & synchronisation

Why would HCG (Human Chorionic Gonadotropin) be used instead of LH? What is it used for?

Longer half life, cheaper

Inducing ovulation

'rig test' - stimulates production of testosterone

What are the functions of oestrogen in males and females?

Males

sexual behaviour

Female

- follicular growth

- optimise possibility of fertilisation

- increased receptivity

- trigger onset of parturition

- optimise chances of fertilisation

- increased growth of mammary gland

When would oestriol be used? What are its adverse effects?

treating urethral sphincter incompetence in spayed bitches

not to be used in whole bitches - impacts mammary glands and brain

adverse effects —> oestrogenic effects

What are the functions of testosterone in the male and female?

Male

- promotes spermatogenesis

- promotes sex gland secretions

- growth and sexual behaviour

Female

- substrate for oestrogen synthesis

- abnormal masculinisation

What is the only androgen used and what is it used for?

Nandralone (synthetic anabolic steroid)

- tissue repair (when excessive tissue breakdown has taken place)

- anaemia associated with renal disease

High doses of androgens inhibit the release of ___

Gonadotrophins

will suppress oestrus cycle

What can androgen receptor antagonists be used to treat? What are their adverse effects and why do they occur?

Used to treat prostatic hyperplasia & male hypersexual behaviour

Male hypersexual behaviour

Reduced ACTH

PUPD

Increased appetite

happens because receptor blockers have a similar structure to progesterone

What does delmadinone acetate do? What is it used to treat?

Inhibit FSH & LH -> decreases testosterone

long half life

treat hypersexual behaviour

'chemical castration'

What does progesterone do in females?

Endometrial secretion

Inhibits GnRH release
Inhibits reproductive behaviour
Maintains pregnancy

What do progesterone receptor agonists do? What can they be used for?

Inhibit GnRH release

Prolong luteal phase

Inhibits reproductive behaviour

Oestrus synchronisation

Suppress oestrus

Adverse effects of progestogens

Endometrial hyperplasia, endometritis, pyometria
Inhibition of ACTH

Behaviour changes

Glucocorticoid activity may induce diabetes mellitus

Why are progestogens not given via the oral administration route?

Rapidly inactivated in liver following oral administration

What is the use of the progestogens:

- Altrenogest

- Proligestone

Synchronise oestrus in pigs & horses

Oestrus suppression in cats, dogs & ferrets

receptor antagonists can be used in abortions

Describe progesterone receptor blockers aglepristone

Only licenced in dogs & cats

Reduced progesterone support for pregnancy —> abortion & pyometra, induction of parturition

Binds to glucocorticoid receptors

How do prolactin inhibitors work? e.g. cabergoline

Increase dopamine which inhibits prolactin secretion

What are prolactin inhibitors used for and what are their adverse effects?

Cause galactostasis in false pregnancy

Induces luteolysis and can cause abortions

What are oxytocin receptor agonists used for? Adverse effects?

increase milk ejection

increase myometrial contractions

Can complicate uterine dystocia

What precautions should be taken when administering prostaglandin receptor agonists?

Wear Gloves —> PGF 2a is absorbed through the skin

Risk to pregnant women

Risk to asthmatics —> can cause bronchonstriction

More ___ is produced when it's darker so it can be used to ____ the oestrus cycle in sheep

Melatonin
Bring forward

melatonin implant used in sheep

(opposite effect in horses —> low melatonin allows cyclicity in horses)

What can B2 adrenergic agonists do? Why might they be used?

Relax smooth muscle in myometrium and airways dilate

- delay delivery in cattle

- aid obstetrical manoeuvres in dystocia e.g. malpresentation/malposture

- relax uterus for C section

- facilitate replacement of prolapsed uterus

The red line represents when progesterone is produced by the ____
The orange line represents when progesterone is produced by the ___

CL
Placenta

When the CL produces progesterone, __ is given to terminate the pregnancy

When the placenta produces progesterone ___ is used to induce parturition

PGF 2a

Glucocorticoid agonist

What class of drug could be given to make sure a bitch does not get pregnant and if owners do not want to spay the bitch.

Progesterone receptor blockers —> prevents ovulation and terminates/prevents pregnancy

only licenced for small animals

What are the clinical signs of a false pregnancy in bitches?

Anorexia or weight gain

Beginning to lactate —> can lead to mastitis

Stealing toys (maternal behaviour)

all due to long luteal phase in the bitch

What class of drugs can be used to alleviate false pregnancy symptoms

Dopamine receptor agonists aka prolactin inhibitors —> inhibits lactation

How would you induce parturition in a term pregnant sheep?

Glucocorticoid agonist —> mimic cortisol

progesterone is placenta dependent

How would you induce parturition in a term pregnant sow?

PG F2a (prostaglandin F2a)

progesterone is CL dependent

How would you induce parturition in a pregnant heifer at:

8 month gestation

term pregnant

glucocorticoid agonist —> placenta dependent progesterone

PG F2a (prostaglandin F2a) —> CL dependent progesterone

What injection is often given to mares at stud 24hrs before they are served?

GnRH —> induces LH

OR

HCG (human chorionic gonadotropin)

A local pig farm wants to change from farrowing 20 sows every week  to batch  farrowing 60 sows every three weeks. Piglets are currently weaned at 4 weeks old. How could the farmer use pharmacological agents and/or changes in management to achieve this?

Weaning —> synchronises sows back into oestrus

and use of progesterone

You are presented with a cow that has not been seen bulling i.e. not showing oestrus signs. On ultrasound, the left & right ovary appear as in the picture. How do you suggest this animal is managed.

In the right ovary, corpus luteum present —> cow has ovulated (normal) i.e. gone into oestrus and has been bulling —> farmer may have missed the signs

Give prostaglandin & tell farmer to look out for oestrus signs in next few days

You are presented with a cow that has not been seen bulling. On ultrasound, the left and right ovary appear as in the image. How do you suggest this animal is managed?

Follicles shown but no CL

Could be in anoestrus/beginning of oestrus cycle/follicular phase?

Could revisit to decide?

Assume in follicular phase & just about to ovulate

Give progesterone for 10 days then prostaglandin after the 10 days —> synchronises the oestrus in order to spot the oestrus signs