A. DEFINITION
1. Hormone = chemical substance secreted from tissues or ductless glands into
surrounding tissue or the bloodstream to evoke a specific physiologic response
2. The specific response occurs at a given tissue because of presence of receptors
on those tissues. Knowledge about receptors and binding guides clinical decision-making
- e.g. oxytocin does not dissociate readily from myometrial receptors so, at
some point, continued dosing is not effective.
B. CHEMICAL STRUCTURES
1. Proteins - e.g. LH, FSH. Unique structure in each species, requires unique
assay in each species
2. Steroids - e.g. progesterone, estrogen, testosterone. Same structure in all
species, common assay - Canine progesterone can by assayed using a bovine or
human assay.
C. CONTROL OF HORMONE SECRETION
1. Feedback systems - e.g. increased serum testosterone concentration has negative
feedback on the pituitary, decreasing release of LH
2. Homeostasis - e.g. increased blood glucose stimulates release of insulin
3. Environmental stimuli - e.g. Suckling of neonates stimulates oxytocin release
from the pituitary, daylength controls reproductive function in several species
via the pineal gland
D. ENDOCRINE TISSUES AND THEIR PRODUCTS
1. HYPOTHALAMUS - The hypothalamus is connected directly to the pituitary by
the hypophysial portal system. Hormones released from the hypothalamus are never
in the general circulation.
a. Gonadotropin releasing hormone (GnRH) - causes
release of LH and
FSH from the pituitary
b. Thyrotropin releasing hormone (TRH) - causes
release of TSH from the
pituitary
2. PITUITARY
a. Posterior lobe = neurohypophysis - The actual
cell bodies producing
these hormones are neurons in the hypothalamus, their axons lie in the posterior
pituitary. Neural stimuli cause release of these hormones.
i. Oxytocin
- stimulates mammary gland to cause milk letdown,
gravid uterus at parturition to cause uterine contraction and cervical dilation
b. Anterior lobe = adenohypophysis - This is a
true gland; hormones are
produced and stored here
i. Follicle stimulating
hormone (FSH) - stimulates growth of
follicle on ovary (female) and production of androgen-binding protein to maintain
high intratesticular testosterone concentrations (male)
ii. Luteinizing
hormone (LH) - causes ovulation of mature ovarian follicle, maintains CL on
ovary after ovulation (female), stimulates and sustains testosterone release
and spermatogenesis in testicle (male)
iii. Prolactin -
stimulates mammary gland to promote milk
production, induces maternal behavior
iv. Thyroid stimulating
hormone (TSH) - stimulates thyroid gland
to assemble T3 and T4
v. Adrenocorticotropic
hormone (ACTH) - stimulates adrenal to
produce steroids
3. THYROID - thyroid hormones stimulate oxygen consumption and increased metabolism
in all body tissues. Either hypothyroidism or hyperthyroidism is associated
with poor reproductive function but exact cause-and-effect relationship is not
reported
a. Tri-iodothyronine (T3)
b. Thyroxine (T4)
4. ADRENAL
a. Sex steroids
b. Glucocorticoids
c. Epinephrine, norepinephrine
5. OVARY
a. Follicle
i. Estrogen - stimulates
female sexual development, breeding
behavior, physical changes of heat (vaginal cornification, vulvar swelling,
serosanguinous vulvar discharge)
b. Corpus luteum (CL)
i. Progesterone
- responsible for pregnancy maintenance, uterine
and mammary growth, induction of maternal behavior
ii. Relaxin - relaxes
pubic symphysis, contributes to cervical dilation late in gestation
6. PLACENTA/PREGNANCY-SPECIFIC TISSUES
a. Human - Human chorionic gonadotropin (hCG)
produced by
fetal/placental unit as early as 6 days post-conception. This is what is used
to identify pregnancy in human early pregnancy tests. In dogs, has LH activity.
b. Horse - Equine chorionic gonadotropin (eCG
= PMSG) produced by
endometrial cups. In dog, has FSH and LH activity.
c. Dog - No pregnancy-specific gonadotropins produced.
Some relaxin may be produced at the placenta.
d. Cat - No pregnancy-specific gonadotropins produced,
progesterone
produced by CL and may be produced by the fetal/placental unit
7. TESTICLE
a. Mullerian inhibiting factor (MIF) - inhibits
female ductal development during embryogenesis
b. Testosterone - Stimulates male sexual development
and behavior, spermatogenesis
E) CLINICAL ENDOCRINOLOGY
Hormones may be used for diagnosis or treatment of disorders in small animal
medicine. The chart below briefly describes uses and contraindications or side-effects
of these therapies.
| HORMONE | USE | SIDE-EFFECTS |
|
Progesterone
|
||
| Megestrol acetate (Ovaban) | Estrus suppression | Pyometra, mammary neoplasia |
| Altrenogest (Regumate) | Hypoluteodism (decreased progesterone during pregnancy) | Poor milk production |
| Medroxyprogesterone acetate | Benign prostatic hypertrophy | None with limited use |
|
Estrogen
|
||
| Estradiol cypionate | Pregnancy termination | Pancytopenia (aplastic anemia, leucopenia, thrombocytopenia), pyometra |
| Diethylstilbestrol (DES) | Urethral sphincter mechanism incompetence | None- no toxic effects have been reported with low doses of this oral estrogen |
| Vaginitis | None | |
| Estrus induction | Variable efficacy | |
|
Testosterone
|
||
| Testosterone cypionate | Estrus suppression | Not approved for use in breeding bitches |
| Libido enhancement | May decrease sperm production if used repeatedly | |
| Mibolerone (Cheque) | Estrus suppression | Must be started one month before estrus onset is expected; not approved for use in breeding bitches |
| Finasteride (Proscar or Propecia) | Benign prostatic hypertrophy | None |
|
Glucocorticoids
|
||
| Dexamethasone | Pregnancy termination | PU/PD |
|
Miscellaneous hormones
|
||
| Oxytocin | Dystocia | Do not use in obstructive dystocia. In all instances causes placental separation. |
| Milk letdown and pair bonding | None | |
| Gonadotropin releasing hormone (GnRH) | Ovulation induction | None |
| Human chorionic gonadotropin (hCG) | Ovulation induction | None |
| Prostaglandin F2alpha (Lutalyse) | Pregnancy termination | Salivation, vomiting, diarrhea, panting |
| Relaxin | Pregnancy diagnosis | --- |
STUDY AND REVIEW GUIDE
1. Describe how tissues "know" to which hormones they can respond.
2. Name four species whose estrous cycle is dependent on daylength. Describe the pathway from change in daylength to onset of estrous behavior.
3. Which four hormones could be administered to dogs to induce ovulation? Are all of these commercially available?
4. Name two stimuli causing release of oxytocin in bitches or queens. Is there an advantage to treating bitches or queens with oxytocin after parturition as a "clean out" shot?
5. FSH is used as an indicator of reproductive function in men. Do you think FSH goes up or goes down in men with reproductive dysfunction? Explain your answer.
6. If you wish to terminate pregnancy in bitches or queens, what hormone's production must be stopped? How will you do that in bitches? In queens?
7. You are presented with a spayed cat who is showing signs of heat. What are two possible tissue sources of estrogen production?
8. A bioassay is indirect assessment of a hormone by evaluation of physical
or cellular changes. Name three bioassays for estrogen in dogs.