Clinical Application of Reproductive Hormones and Related Substances

Animal Reproduction

• The process of reproduction in all farm animals begins with exhibition of cyclical activity after attaining age of puberty.
• The start of biological clock (estrus cycle) is a complex process and is under the control of hypothalamus- pituitary – ovarian axis.
• On both side of this axis there are further influences of area like extra – hypothalamus (especially in seasonal breeders) which exert their influence by olfaction, touch and light etc on the activity of hypothalamus while on the other end, the uterus has its influence in controlling the activity of ovary.
• Hormones secreted from hypothalamus, pituitary, ovary and uterus controlling reproductive cycle is popularly called as reproductive hormones.
• Chemically these reproductive hormones are protein, glycoprotein, steroid and fatty acid in nature.
• A successful reproductive processes is one where a female shows normal cyclical activity, get pregnant with in the duration of three estrus cycle, carry a fetus to term, deliver a viable calf after full gestation with normal expulsion of fetal membrane and again become pregnant within 60 days post partum.
• For a cow expectation of normal reproduction is denoted by producing a calf a year.
• Life time production (in terms of lactation yield and live calf crop) of a female is affected when animals face problem of infertility.
• In view of keeping optimum fertility let us discuss clinical application of various reproductive hormones.

Clinical Application

1. GnRH (Gonadotrophin releasing hormone)

Commercially available preparation

• Fertirelin (Ovalyse, Upjohn Ltd)
• Gonadorelin (Fertagl,Cystorelin Intervet Animal health, UK Ltd)
• Buserelin (Receptal, 2-5mi/5ml /10ml MSD)

Pharmacological Action

Stimulates endogenous release of FSH & LH

Indications

1. Follicular Cyst/ Partially lutenized cyst
2. Delayed ovulation
3. Anovulation
4. True anoestrus
5. Silent oestrus
6. Improve conception rates (12thday post service or insemination)
7. Acyclicity
8. As a part ofestrus synchronization regimens/ov-synch programme

Dose rate

• Fertireline : 100 ug, i.m
• Gonadorelin : 0.5 mg, i.m, s.c. or i.v
• Buserelin : 0.5 mg, i.m, i.v. or s.c

2. Oxytocin

Commercially available preparation

• Syntocinon (Novartis)
• Meritocin (Mercury Lab)
•  Pitocin( 5 unit /ml ,1ml amp)

Pharmacological Action

causes myometrial contraction & letting down of milk

Indications

1. Induces milk let down
2. Hastens uterine involution (following dystocia, caesarean operation, and replacement of uterine prolapse).
3. Haemostatic in uterine trauma or haemorrhage.
4. Treatment of uterine inertia
5. Expulsion of retained placenta

Dose rate

• Large animals : l0 IU i.m. or i.v. as incremental dose to a maximum between 40-100 IU.
• Small animals : 2-5 IU i.m. or i.v.

Precaution

• For best result use increasing incremental dose rate of the drug
• Prefer i.v. adminstration
• High dose cause uterine spasm rather than synchronized contration

3. FSH (Follicle stimulating hormones)

Commercially available preparation

• eCG or Equine Chorionic Gondotrophin (Folligon,1000 IU/ vial PMSG Intervet UK; Trophovet, indian Immunologicals, India, Fostin 600 Pfizer).
• Porcine Pure FSH (Folltropin-V, Vetrepharm, Canada; Superov ( global Genetics UK), Ausa Internations USA

Pharmacological action

Mainly FSH like but has some LH activity

Indications

1. Superovulation of donor cows in ET
2. True anestrus
3. Impaired spermatogenesis in bull
4. Along with intravaginal progesterone sponge to advance the onset of breeding season
5. At the time of withdrawl of intravaginal progesterone preperations when used to treat acyclicity

Dose rate

• Cattle: 1500-3000 IU s.c. or i.m. for superovluation & 500-750 IU S.Cor i.m for true anestrus.
• Sheep and goats: 500 – 800 IU S.C. or I.M.
• Pig: 1000 IU s.c. or i.m.

Precaution

• Dose should be used with caution for treatment of true anestrus in order to avoid sperovulation.

4. LH (Lutenizing hormone)

Commercially available preparation

• Human Chorionic Gonadotrophin (Chorulon, Intervet UK Ltd)
• Human Chorionic Gonadotrophin (Pubergen, SKOYA)

Pharmacological action

Stimulate androgen production from thecal cells of ovary and leydig cells of the testis, stimulate follicular maturation and ovulation, corpus luteum formation and maintenance.

Indications

1. Delayed ovulation
2. Anovulation
3. Ovarian cyst (Follicular Cyst) / Partially lutenized cyst
4. Luteal insfficiency
5. Improve chances of pregnancy in cyclic non-breeders
6. Improve libido in bull

Dose rate

• Large animals: 1500 – 3000 IU i.v. or i.m
• Small animals: 100 – 500 IU i.v. or i.m.

5. Progesterone

Commercially available preparation

• Progesterone releasing intravaginal devices (EASI BREED, CIDR)
• Progesterone in oil (Duraprogen, Proluton 250mg / ml,2/3 ml amp)
• Ear implant (Crester, Intervet UK)

Pharmacological action

Have a negative effect on hypothalamus and pituitary thus stopping cyclical activity.

Indication

1. Estrus/ ovulation synchronization ln cows and heifers with prostaglandin
2. True anoestrus/ acyclicity in cow and heifers
3. Follicular cyst( thin walled)
4. Threatened abortion
5. Treatment of non-observed oestrus in cow

Dose rate

• Sponges and implant usually kept for 12-14 days used in conjunction with PG for synchronization & follicular cyst. For true anestrus sponges and implant kept for 12-14 days.
• Large animal : 500 mg i.m. at weekly interval for 5 weeks in cases of threatening of abortion.

6. Estrogen

Commercially available preparation

• Oestradiol benzoate ( 5mg /ml inj, Intervet UK Ltd)
• Oestradiol valerate(Progynon Depot10mg /ml inj, German Remedies)

Pharmacological action

Stimulate changes in tubular genital tract, which control gamete transport and with progesterone causes development of mammary gland. Potentiate ecbolic action of oxytocin  and preovulatory surge of gondotrophins.

Indications

1. Ripening of the cervix /ICD along with other hormones
2. Induce lactation
3. Misalliance in bitch
4. Mummificatin
5. Maceration
6. Pyometra
7. Uterine Inertia
8. Uterine Infection
9. Urinary incontinence in the spayed bitch
10. Prostatic hyperplasia and anal adenoma in the male dog
11. To depress hypersexuality in the male dog

Dose rate

• Ripening of the cervix in large animals, 30 mg
• Misalliance in bitch 0.1 mg/kg to a maximum of 3 mg within 24h of misonating

7. PGF2a

Commercially available preparation

• Dinoprost (Lutalyse, 5mg /mlUpjohn Ltd)
• Cloprosteno l( Vetmate/ Pragma/ Cyclix)
• Luprostiol (Prosolvin,7-5 mg /ml Intervet)
• Tiaprost (illiren, Hoechst)

Pharmacological action

Potent luteolytic agent (PGF2a) excepts in bitch and cat. Plays role in ovulation, parturition and gamete transport, have short biological half-   life.

Indication

1. Synchronization of estrus
2. Induction of parturition
3. Subestrus/ silent oestrus
4. Induction of abortion
5. Expulsion of mummified fetus
6. Closed pyometra
7. Treatment of luteal cyst
8. As a part ofestrus synchronization regimens
9. Pyometra
10. Traetment of endometritis

Dose rate

• Dinoprost: Catlle, 25 -35 mg, Horse, 20 mg, Sheep , 5-10 mg, Dog, 0.25 –                                   0.5 mg/kg. I.m
• Cloprostenol:500 mg, i.m.
• Luprostiol, Cattle, 15 mg, Horse, 7.5 mg, Sheep & Goat, 7.5 mg i.m

9. Antiprogestogens

Commercially available preparation

Aglepristone( Alizan virbac UK Ltd)

Pharmacological action

Prolactin inhibitors such as cabergoline inhibits endogenous progesterone production and secretion by the corpora lutea in the bitch. Because prolactin is the main luteotrophic hormone in this species and thus can terminate pregnancy.It is a progesterone receptor antagonist exerts its effect by blocking the action of progesterone at cellular and tissue level while the concentrations of the hormone in the peripheral blood are unaffected.

Indications

Termination of unwanted pregnancy in the bitch up to 45 days of gestation

Dose rate

Bitch-10mg/kg sc repeat after 24 hours

9. Androgens

Commercially available preparation

• Testosterone esters injection durateston intervet uk contains Testosterone Decanoate 20mg / Ml,
• Testosterone Isocaproate 12mg / Ml,
• Testosterone Phenyl Propionate 12mg / ml,

Pharmacological action

Since testosterone is involved in controlling libido in the male it is used to improove any deficiency that might be present.,although it must be stressed that libido and sexual behavior are complex and not just a reflection of endogenous androgens.,therefore the results of this therapy will usually be disappointing.

.Indications

• Used to improve libido
• Androgens have anabolic effects and can be used to treat debilitated animals.
• They has been used to postpone estrus in bitches and overcome some of the behavioural problems associated with pseudopregnancy in bitches, and reverse faminization associated with sertoli cell tumours

Dose rate

• 0.05 to 0,1 ml/ kg SC or IM in dog and cat

10. Anti-androgens

Commercially available preparation

Delmadenone acetate (Pfizer)

Pharmacological action

These substances are progestogens and are used to counteract the behavioral actins of endogenous androgens.

Indications

1. Hypersexuality in the male dog.
2. Prostatic hyperplasia and prostatitis

Dose rate

• 1.0-2.0/ kg body weight SC or IM

11. Prolactin -antagonist

Commercially available preparation

• Cabergoline(Galastop, Ceva UK Chesham) A viscous, non-aquos solution containing 50mg/ ml cabergoline.

Pharmacological action

It  is a long acting prolactin inhibitors that because of the role of this hormone in initiating the sign of pregnancy and overt signs of pseudo-pregnancy,can cause their reversal in the bitch.

Indications

1. Treatment of overt pseudo-pregnancy in the bitch, orally at a dose rate of 0.1mg/kg daily for 4-6 consecutive days.
2. It is sometimes successful in suppressing lactation in goats.

References

1. Novakis D,E, Parkinson T. J. and England Gary C.W. (2009)Veterinary reproduction and obstetrics