HORMONES ODF VETERINARY THERAPEUTIC IMPORTANCE

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PITUITARY HORMONES
The pituitary gland is divided into two parts: anterior (cranial) and posterior (caudal)
• Anterior pituitary hormones used in veterinary practice include:
– Thyroid stimulating hormone (TSH)
– Adrenocorticotropic hormone (ACTH)
– Follicle stimulating hormone (FSH)
– Luteinizing hormone (LH)
– Growth hormone (GH)
 • Posterior pituitary hormones used in veterinary practice include:
– Antidiuretic hormone (ADH)
– Oxytocin
Anterior Pituitary Gland Hormones
• TSH is used in the diagnosis of primary hypothyroidism
• ACTH is used to stimulate the adrenal cortex to secrete corticosteroids in the
diagnosis of adrenal cortex disease
• FSH and LH (see reproductive section)
• GH is used to increase growth rate and feed use efficiency in livestock and
increase milk production in dairy cows

Posterior Pituitary Gland Hormones

• ADH is used to treat diabetes insipidus (disease characterized by the inability to

concentrate urine due to insufficient amounts of ADH)
• Oxytocin is used to aid in uterine contraction and induce labor in animals at term,
expel the placenta, induce milk letdown, and as an adjunct therapy for animals
with open pyometra
Hormones of the Pancreas

• The pancreas secretes two hormones that help regulate blood glucose
– Insulin responds to a rise in blood glucose and promotes the uptake and
use of glucose for energy in cells
– Glucagon increases blood glucose levels by promoting the breakdown of
glycogen into glucose
• Diabetes mellitus is a disease of fat, carbohydrate, and protein metabolism caused
by lack of or inefficient use of insulin
– Treated both with diet changes and medically

• Insulin is used to treat diabetes mellitus by keeping blood glucose in the proper
range
• Sources of insulin include pork, synthetic, and recombinant forms
• Onset and duration of insulin action are controlled by modifying the regular
insulin structure
– Short-acting is used for initial treatment of diabetic ketoacidosis and keep
blood glucose stable (regular crystalline insulin, semilente)
– Intermediate-acting is used to control blood glucose in uncomplicated
cases of diabetes mellitus (NPH and lente)
– Long-acting is used to control blood glucose for longer periods of time,
especially in cats (protamine zinc insulin and ultralente)

Thyroid Hormones
Diseases Involving Thyroid Hormones
Hypothyroidism is characterized by a deficiency of thyroid hormone
• Signs of hypothyroidism include decreased coat and hair luster, weight gain,
listlessness, intolerance to cold, and reproductive failure
 • Diagnosed by measuring serum total T4 and T3 or by a thyroid stimulation test or
by the thyrotropin releasing hormone response test
• Hypothyroid animals are treated with thyroid replacement therapy
– levothyroxine (T4)
– liothyronine (T3)
Hyperthyroidism is characterized by an increased production of thyroid hormone
• Signs of hyperthyroidism include increased thirst, weight loss, increased stool
production, restlessness, and tachycardia
• Diagnosed by measuring serum total T4 and T3
• Hyperthyroid animals are treated with antithyroid drugs or surgical removal
– Radioactive isotopes of iodine (I-131) destroy the thyroid gland
– Methimazole: interferes with the incorporation of iodine in the molecules
of T4 and T3
– Propylthiouracil (PTU): interferes with the conversion of T4 to T3
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GONADOTROPINS

Chemistry: Glycoproteins ; 92 amino acid a subunit (identical to that of TSH) ß subunits

which confer biological specificity:
a) Pituitary Gonadotropins : Luteinizing hormone ( LH) - 115 aa; Follicle stimulating
hormone (f FSH)- 115 aa. Both can be obtained in semipurified form, but expensive.
Porcine FSH(pFSH) and recombinant derived FSH are used to induce superovulation in
donor cows for embryo transfer.
b) Non Pituitary Gonadotropins: human Chorionic gonadotropin (hCG)- 145 aa_ ;
Pregnant mare serum gonadotrophin (PMSG/eCG)

Gonadotropins used clinically

LH activity: Human chorionic gonadotropin (hCG)
Equivalent LH and FSH activity: Human menopausal gonadotropin (hMG; menotropin)
FSH activity: Urofollitropin (uFSH) Pregnant mare serum gonadotrophin (PMSG/equine
chorionic gonadotrophin;eCG), Menotropin with LH component removed Recombinant
human FSH (rFSH)

Actions:
In the female: FSH:stimulates development of ovarian follicles,
LH stimulates production of estrogen and progesterone, induces ovulation
In the male: FSH stimulates production of androgen-binding globulin
maintains high testosterone levels in the seminiferous tubules required for
spermatogenesis, LH stimulates production of testosterone

Indications of FSH ( PMSG)

• Superovulation in donor cows for embryo transfer
• Impaired spermatogenesis in bulls
• Induce oestrous in physiological anoestrus in bitches
 • In association with hCG to stimulate onset of cyclical activity after fasrrowing in
pigs.
• In association woith intravaginal progestogen sponges to advance the onset of
breeding season in sheep and goats
• Dose: 1500- 300IU, SC or IM(cattle); 500-800IU, SC or IM(sheep and goat); 50-
200IU, SC or IM(dog); 1000I U, SC or IM(pig)

Indications of LH (hCG)
• Delayed ovulation and anovulation, ovarian cysts, luteal deficiency, improving
conception rate, improving libido in cattle , pigs, sheeps, goat andf horses
• To induce ovulation in cats, to curtail prolonged or persistent prooestrus/oestrus
in bitches.
• Dose: 1500- 300IU, IV or IM(cattle and horse); 100- 500 IU, SC or IM(sheep
and goat); 100-500 IU, SC or IM(dog); 500-1000I U, IV or IM(pig), 100-200 IU
(cat)
GnRH AND ANALOGS
GnRH: Chemistry: single chain 10 amino acid peptide
Pyro-Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly
• Secretion by the hypothalamus is driven by a pulse generator that is regulated by
negative feedback of the gonadal hormones
• Binds to specific G protein-coupled receptor
• Frequency and amplitude of GnRH pulses determines the secretion of each
gonadotropin
• Biologic preparation very costly, hence synthetic GnRH analogs are used.
Hormone preparations used clinically: are Synthetic GnRH (gonadorelin hydrochloride)
peptide analogues:
Used for pulsatile administration examples: Long-acting synthetic agonists-
Buserelin acetate, Leuprolide acetate Histrelin acetate ,Nafarelin acetate,
Goserelin acetate, fertyilerin, deslorelin

Indications:
• Follicular cysts
• Delayed ovulation, anovulation
• Acycl;icity- anoestrus, suboestrus,
• Improved conception rate after inseminationm
• In oestrus synchronisation

• Dose: Buserelin; cow. 10-20µg; horse, 40 µg, IM, IV, SC; gonadorelin: cow,
0.5mg, IM,SC,IV, Fertilerin, cow, 100 µg,IM

GnRH Antagonists: Ganirelix acetate, Cetorelix acetate are NRH analogs

competitive antagonists of the GnRH receptor ⇓ LH secretion > than FSH
Used to inhibit premature LH surges during the early to mid-follicular phase in women
undergoing controlled ovarian stimulation for treatment of infertility
A low dose is given SQ beginning on day 5 or 6 and continued daily until the day of hCG
administration . Do not induce a transient increase in gonadotropins

DRUGS AFFECTING REPRODUCTION

• Androgens are male hormones
– Testosterone:
• Made in the interstitial cells of the testes
• Examples:
– Testosterone cypionate in oil
– Testosterone enanthate in oil
– Testosterone propionate in oil
– Danazol
– Methyl testosterone
• Used to treat conditions such as infertility and hypogonadism,
produce estrus detectors, and for testosterone-responsive urinary
incontinence in dogs. Also used to treat debilitated aniumals
because of their anabolic effects, used to postpone oestrus in
bithches, to overcome behavioural problems associated wioth
pseudopregnancy. And reverse feminization associated with sertoli
cell tumour.
•
– Mibolerone:
• Blocks the release of LH from the anterior pituitary gland;
therefore the follicle does not fully develop
• Used to prevent estrus in adult female dogs and the treatment of
false pregnancies
– Zinc gluconate neutralized by arginine:
• Nonsurgical neutering drug
• Chemical sterilant approved for use in 3- to 10-month-old male
dogs
• Used as an intratesticular injection
Antiandrogens: These are progestogens, are used to counteract the behavioural
actions of endogenous androgens.
They are indicated to control hypersexuality in male dogs, and to treat prostatic
hyperplasia and proststis in dogs
Eg: Delemidinone acetate, danazol, flutamide, bicalutamide, cyproterone acetate
Finasteride( 5-alpha reductase inhibitor; not a specific antiandrogen)
• Female hormones
– Estrogen:
• Promotes female sex characteristics and stimulates and maintains
the reproductive tract
• Synthetic estrogens are used in dogs to prevent implantation of
fertilized ova and to correct urinary incontinence, vaginitis, and
dermatitis
 • Synthetic estrogens are used in cattle to treat persistent corpus
luteum, aid in expulsion of retained placentas and mummified feti,
and to promote weight gain
• Synthetic estrogens are used in horses to induce estrus in the
nonbreeding season
• Examples:
• Natural : estradiol, estrone, estriol
• Semisynthetic: ethinyl oestradiol, esters like estradiol benzoate,
cypionate, propionate, valerate, ethenate., diethyl stilbestrol.
• Synthetic: mestranol, tibolone, hexestrol, dienestrol, diphenyl
ethylene(stilbene)etc.

Indications:
• Endometritis treatment in cattle(contraindicated in acute toxic metritis), to tone atonic
uterus
• Prevention of unplanned pregnancy / mismating in bithches, urinary incontinence in
spayed bitches,
• prostatic hyperplasia and adenoma in male dog, to depress hypersexuality in male dog.
• Ripening of cervix before oxytoin induced foaling in horse
• To induce artificial lactation in cattle

Antioestrogens (nonsteroidal) :
Clomiphene citrate, tamoxifen citrate, centchroman
Primarily indicated in conditions of anovulatory oestrus, low sperm counts in males,
breast cancer in females
Progestogens: (Progestins)

Reproductive effects of progesterone:

Numerous reproductive studies on progesterone and other progestins demonstrate that

their administration can have actions that can be classified as progestational, anti-
estrogenic, anti-androgenic, anti-gonadotrophic, and contraceptive. However, under some
circumstances, the same compound(s), in at least some species, may acutely stimulate
gonadotrophin secretion, have an androgenizing effect, or have self-limiting
progestational effects.

1. Progestational actions. Pregnancy supporting actions of progesterone and other

progestins include the following:
1. stimulation of endometrial gland development and secretion by acting on
progesterone receptors, especially after estrogen priming of the
endometrium;
2. promotion of cervical closure;
3. suppression of uterine motility by depressing myometrial sensitivity and
contractility directly; and also by decreasing the availability of myometrial
oxytocin receptors;
 4. stimulating proliferation of mammary tissue, especially lobulo-alveolar
tissue.
2. Anti-estrogenic action. Prior progestin administration reduces or prevents
estrogen-induced phenomena including vaginal bleeding, estrus behavior, and
ciliation of the oviduct by suppressing the synthesis of estrogen receptors
normally stimulated by exposure to estrogen.
3. Anti-androgenic action. Progestin administration reduces, inhibits or reverses
some effects of androgen, including libido (sex drive), possibly by interfering
with androgen or other steroid receptors’ responses to their own hormone ligands,
in addition to any anti-gonadotrophic action.
4. Anti-gonadotrophic action. Progestin administration, through an ability to reduce
or modulate secretion of the gonadotrophins LH and FSH secretion, can suppress
follicle development and prevent ovulation. Progestins do not appear to lower
basal gonadotrophin secretion, but rather appear to prevent increases in pulsatile
gonadotrophin secretion that would normally otherwise occur in a normal ovarian
cycle.
5. Contraceptive actions. Progestins, via multiple mechanisms, can prevent,
diminish, or desynchronize normal changes in the reproductive tract, prevent
follicle maturation and ovulation, and interfere with sperm transport.

The anti-gonadotrophic action is by far and large the most important clinical effect in
small animal reproduction. Administration of a progestin to an intact bitch or queen will
invariably cause some degree of suppression of ovarian cycles. However, the same
dosage of a progestin will have different effects on the cycle depending on time of
treatment relative to stage of estrous cycle. The side effects can vary depending on
whether treatment is administered prior to the onset of proestrus, after the onset of
proestrus, during estrus, during metestrus, or during anestrus; Likewise, duration of
efficacy can vary - cycles may resume after days, weeks or months, respectively (

Progestational Compounds Used in Veterinary Medicine

medroxyprogesterone acetate, megestrol acetate and proligestone , delmadinone

acetate, chlormadinone acetate, and norethisterone acetate

Melengestrol acetate ] and ally-trenbolone have been experimentally tested in bitches,

while more recently the contraceptive action of levonorgestrel has been experimentally
tested in cats]. All of these modified steroids are orally active. Some progestins are
marketed in both tablet formulations of oral administration, and liquid solutions or
suspensions for injection or depot-injection. Progesterone itself is not orally active, and it
is only marketed in injectable formulations.

Indications: Prolonged postponement / Temporary Postponement / Suppression

(proestrus administration) (anestrus administration (anestrus administration) , Uterine
Hemorrhage, Pregnancy Failure, Pseudopregnancy, Lactation, Nymphomania

Side Effects :
1. Increased Incidence of Uterine Pathology; High doses of progestin, or repeated or
prolonged exposure to moderate doses of progesterone or progestins will cause cystic
endometrial hyperplasia (CEH).

2. Increased Incidence of Mammary Tumors

3. Increased Secretion of Prolactin

4. Increased Secretion of GH and Acromegalic Changes

5. Diabetes Mellitus

6. Masculinization of Female Fetuses

7. Adrenocortical Suppression

Dosages: Medroxyprogesterone Acetate- 2.5 - 3.0 mg/kg IM every 5 months, while it is

2.0 mg/kg IM every 5 months for the feline]. Megestrol Acetate-In 2.5
mg/cat/day.

Proligestone- 100 mg/kg SC at sequential intervals of 3, 4 and 5 months, and at intervals

of 5 months thereafter.

PRID: ( Progesterone releasing intravaginal device): device containing progesterone an

d estradiol ester, used for synchronization of oestrous/ ovulation in cows and
heifers , in combination with PGF2 α. The device is is inserted in to vagina nd
kept insitu for 12 days, PGF2 α is administered 24 hours befor removal to
improve the effectiveness of the synchronization. Oetrus occurs after 2-5 days of
withdrawl.

Antiprogestins
Antihormones have the ability to bind particular hormonal receptors without eliciting a
hormonal message or action Often, antihormones increase the synthesis and plasma
concentrations of other hormones by the inhibition of the normal
feedback control of those hormones.
Antiprogestins are synthetic steroids which bind with great affinity to progesterone
receptors without any of the effects of
progesterone. In bitches, two antiprogestins have been studied: mifepristone (RU 486)
and aglepristone (RU 534) . Mifepristone is a progesterone and glucocorticoid antagonist.
It is more potent as an anti-progestin than as an anti-corticoid.
In the absence of progesterone or cortisol, mifepristone can have a moderate agonistic
effect
To improve its efficacy, mifepristone is currently used in combination with low doses of
prostaglandin analogs such as misoprostol.
Mifepristone
 In pregnant bitches, mifepristone was effective if administered after day 30 of gestation .
The protocol used was the oral administration of 2.5 mg/kg, twice a day for 4 to 5 days.
Pregnancy was terminated without side effects within 3 to 4 days after treatment.
Aglepristone
This drug can be used for pregnancy termination from mating date until 45 days after
mating

Prostaglandins and PG analogusI:

Natural PGF2 α ( dinoprost, carboprost ) and its synthetic analogs( Cloprostenol,

luprostiol, , tiaprost ) are potent luteolytic agents, except in bitch and cat.

Indications:

Cattle:, Horse, sheep and goats

rus synchronization in cow and heifers

tmwent of silent heat/ nonobserved oestrus.
ction of parturition /foaling/farrowing
ction of abortion and expulsion of mummified fetus
atment of pyometra and Endometritis
tment of luteal cysts
dopregnancy in goats

Bitches: treatment of open pyometra and termination of pregnancy / mismating in

combination with Antiprogestin.

Dose: Dinoprost, 25-35mg( 5ml)), cattle; 5mg horse, 10mg, pig; 0.25-0.5mg/kg-bitch,
all IM. Cloprostenol -250-500µg,IM, 125-250µg, pig,IM; luprostiol- 15mg,
cattle, IM